From f186ceabc63aa00262ddf2830a7d95b203595bbe Mon Sep 17 00:00:00 2001 From: Daniel Silva Date: Mon, 23 Jan 2023 18:40:56 -0500 Subject: [PATCH] feat: get details about a author's papers --- semanticscholar/SemanticScholar.py | 47 +- tests/data/test_get_author_papers.yaml | 28713 +++++++++++++++++++++++ tests/test_semanticscholar.py | 12 + 3 files changed, 28771 insertions(+), 1 deletion(-) create mode 100644 tests/data/test_get_author_papers.yaml diff --git a/semanticscholar/SemanticScholar.py b/semanticscholar/SemanticScholar.py index fb4bba3..9b95284 100644 --- a/semanticscholar/SemanticScholar.py +++ b/semanticscholar/SemanticScholar.py @@ -155,7 +155,7 @@ def get_papers( papers = [Paper(item) for item in data] return papers - + def get_paper_authors( self, paper_id: str, @@ -404,6 +404,51 @@ def get_authors( return authors + def get_author_papers( + self, + author_id: str, + fields: list = None, + limit: int = 1000 + ) -> PaginatedResults: + '''Get details about a author's papers + + :calls: `POST /paper/{author_id}/papers \ + `_ + + :param str paper_id: S2PaperId, CorpusId, DOI, ArXivId, MAG, ACL,\ + PMID, PMCID, or URL from: + + - semanticscholar.org + - arxiv.org + - aclweb.org + - acm.org + - biorxiv.org + + :param list fields: (optional) list of the fields to be returned. + :param int limit: (optional) maximum number of results to return\ + (must be <= 1000). + ''' + + if limit < 1 or limit > 1000: + raise ValueError( + 'The limit parameter must be between 1 and 1000 inclusive.') + + if not fields: + fields = Paper.SEARCH_FIELDS + + url = f'{self.api_url}/author/{author_id}/papers' + + results = PaginatedResults( + requester=self._requester, + data_type=Paper, + url=url, + fields=fields, + limit=limit + ) + + return results + def search_author( self, query: str, diff --git a/tests/data/test_get_author_papers.yaml b/tests/data/test_get_author_papers.yaml new file mode 100644 index 0000000..1092a90 --- /dev/null +++ b/tests/data/test_get_author_papers.yaml @@ -0,0 +1,28713 @@ +interactions: +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=0&limit=100 + response: + body: + string: '{"offset": 0, "next": 100, "data": [{"paperId": "08d38971193f866694eb9bdbc4ca6e2f37857d8d", + "externalIds": {"DOI": "10.1158/1078-0432.CCR-22-2270", "CorpusId": 255463401, + "PubMed": "36595567"}, "corpusId": 255463401, "publicationVenue": {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", + "name": "Clinical Cancer Research", "type": "journal", "alternate_names": + ["Clin Cancer Res"], "issn": "1078-0432", "url": "https://clincancerres.aacrjournals.org/", + "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/08d38971193f866694eb9bdbc4ca6e2f37857d8d", + "title": "Genetic heterogeneity and tissue-specific patterns of tumors with + multiple PIK3CA mutations.", "abstract": "PURPOSE\nTo comprehensively characterize + tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) + mutations and assess their impact on potential therapeutic outcomes.\n\n\nEXPERIMENTAL + DESIGN\nWe profiled a pan-cancer cohort comprised of 352,392 samples across + 66 tumor types using a targeted hybrid capture-based next generation sequencing + panel covering at least 324 cancer-related genes. Molecularly defined subgroups, + allelic configuration, clonality, and mutational signatures were identified + and tested for association with PI3K inhibitor therapeutic response.\n\n\nRESULTS\nMulti-PIK3CA + mutations are found in 11% of all PIK3CA-mutant tumors, including 9% of low + tumor mutational burden PIK3CA-mutant tumors, and are enriched in breast and + gynecologic cancers. Multi-PIK3CA mutations are frequently clonal and in cis + on the same allele and occur at characteristic positions across tumor types. + These mutations tend to be mutually exclusive of mutations in other driver + genes, and of genes in the PI3K pathway. Among PIK3CA-mutant tumors with a + high TMB, 18% are multi-PIK3CA mutant and often harbor an APOBEC mutational + signature. Despite large differences in specific allele combinations comprising + multi-PIK3CA mutant tumors, especially across cancer types, patients with + different classes of multi-PIK3CA mutant ER+ HER2- breast cancers respond + similarly to PI3K inhibition.\n\n\nCONCLUSIONS\nOur pan-tumor study provides + biological insights into the genetic heterogeneity and tissue specificities + of multi-PIK3CA mutations, with potential clinical utility to guide PI3K inhibition + strategies.", "venue": "Clinical Cancer Research", "year": 2023, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-22-2270/3237674/ccr-22-2270.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2023-01-03", "journal": + {"name": "Clinical cancer research : an official journal of the American Association + for Cancer Research"}, "authors": [{"authorId": "40088390", "name": "S. Sivakumar"}, + {"authorId": "3287834", "name": "D. Jin"}, {"authorId": "2199403555", "name": + "Ruchita Rathod"}, {"authorId": "2150933707", "name": "J. Ross"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2158234116", "name": "Maurizio + Scaltriti"}, {"authorId": "2115896184", "name": "Jessica W. Chen"}, {"authorId": + "2807476", "name": "Katherine E. Hutchinson"}, {"authorId": "2017652", "name": + "T. Wilson"}, {"authorId": "48156320", "name": "E. Sokol"}, {"authorId": "35123724", + "name": "N. Vasan"}]}, {"paperId": "31b70de325b76347e3025102a850f3ac513660fd", + "externalIds": {"DOI": "10.1038/s41586-022-05575-3", "CorpusId": 255748612, + "PubMed": "36631611"}, "corpusId": 255748612, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/31b70de325b76347e3025102a850f3ac513660fd", + "title": "An atlas of substrate specificities for the human serine/threonine + kinome.", "abstract": null, "venue": "Nature", "year": 2023, "referenceCount": + 77, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.nature.com/articles/s41586-022-05575-3.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2023-01-11", "journal": {"name": "Nature"}, + "authors": [{"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "5247030", "name": "Tomer M. Yaron"}, {"authorId": "2137359212", "name": "Emily + M. Huntsman"}, {"authorId": "14658204", "name": "A. Kerelsky"}, {"authorId": + "2200176181", "name": "Junho Song"}, {"authorId": "2166242001", "name": "Amit + Regev"}, {"authorId": "2115348830", "name": "Ting Lin"}, {"authorId": "51910553", + "name": "Katarina M Liberatore"}, {"authorId": "2152463969", "name": "Daniel + M. Cizin"}, {"authorId": "2055611292", "name": "B. M. Cohen"}, {"authorId": + "35123724", "name": "N. Vasan"}, {"authorId": "50032234", "name": "Yilun Ma"}, + {"authorId": "49181291", "name": "Konstantin Krismer"}, {"authorId": "2124145062", + "name": "Jaylissa Torres Robles"}, {"authorId": "49094504", "name": "B. van + de Kooij"}, {"authorId": "1601471755", "name": "Anne van Vlimmeren"}, {"authorId": + "1447106051", "name": "Nicole Andr\u00e9e-Busch"}, {"authorId": "2007005", + "name": "N. K\u00e4ufer"}, {"authorId": "6547314", "name": "M. Dorovkov"}, + {"authorId": "4097704", "name": "A. Ryazanov"}, {"authorId": "49710109", "name": + "Y. Takagi"}, {"authorId": "4306515", "name": "Edward R. Kastenhuber"}, {"authorId": + "145524334", "name": "M. Goncalves"}, {"authorId": "48821307", "name": "B. + Hopkins"}, {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": + "34762957", "name": "D. Taatjes"}, {"authorId": "4165148", "name": "A. Maucuer"}, + {"authorId": "144561115", "name": "A. Yamashita"}, {"authorId": "145919811", + "name": "A. Degterev"}, {"authorId": "1942601", "name": "Mohamed Uduman"}, + {"authorId": "2200206589", "name": "Jingyi Lu"}, {"authorId": "47507246", + "name": "S. Landry"}, {"authorId": "2119454508", "name": "Bin Zhang"}, {"authorId": + "2200155031", "name": "Ian Cossentino"}, {"authorId": "1892258", "name": "R. + Linding"}, {"authorId": "4037343", "name": "J. Blenis"}, {"authorId": "46627576", + "name": "P. Hornbeck"}, {"authorId": "25581223", "name": "B. Turk"}, {"authorId": + "88402408", "name": "M. Yaffe"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "a76bb671101e536b0aead09cf315bf7f10a57c21", "externalIds": {"DOI": + "10.1101/2022.03.09.483647", "CorpusId": 255776016}, "corpusId": 255776016, + "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": + "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/a76bb671101e536b0aead09cf315bf7f10a57c21", + "title": "NAK associated protein 1/NAP1 is required for mitosis and cytokinesis + by activating TBK1", "abstract": "Subcellular location and activation of Tank + Binding Kinase 1 (TBK1) govern precise progression through mitosis. Either + loss of activated TBK1 or its sequestration from the centrosomes causes error + in mitosis and growth defects. Yet, what regulates its recruitment and activation + on the centrosomes is unknown. We identified that NAK Associated Protein 1 + (NAP1) is essential for mitosis which binds to TBK1 on the centrosomes to + activate it. Loss of NAP1 causes several mitotic and cytokinetic defects due + to inactivation of TBK1. Our quantitative phosphoproteomics identified numerous + TBK1 substrates that are not only confined to the centrosomes but also are + associated with microtubules. Substrate motifs analysis indicates that TBK1 + acts upstream of other essential cell cycle kinases like Aurora and PAK kinases. + We also identified NAP1 as a TBK1 substrate at S318 promoting its degradation + by ubiquitin proteasomal system acting as a negative regulatory step. These + data uncover an important distinct function for the NAP1-TBK1 complex during + cell division.", "venue": "bioRxiv", "year": 2023, "referenceCount": 102, + "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.biorxiv.org/content/biorxiv/early/2022/03/10/2022.03.09.483647.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2023-01-11", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "1387837394", "name": "Swagatika Paul"}, + {"authorId": "2817135", "name": "Shireen A. Sarraf"}, {"authorId": "2179009294", + "name": "Ki Hong Nam"}, {"authorId": "2158669194", "name": "Leila Zavar"}, + {"authorId": "1491128989", "name": "Sahitya Ranjan Biswas"}, {"authorId": + "1401161913", "name": "Lauren E. Fritsch"}, {"authorId": "2042247002", "name": + "Nicole DeFoor"}, {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": + "145916288", "name": "Jared L. Johnson"}, {"authorId": "2137359212", "name": + "Emily M. Huntsman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4096885", "name": "A. Ordureau"}, {"authorId": "6458611", "name": "Alicia + M. Pickrell"}]}, {"paperId": "1e1722c24354818457609a4a04df2345237045b3", "externalIds": + {"DOI": "10.1158/1541-7786.MCR-22-0804", "CorpusId": 253267506, "PubMed": + "36325685"}, "corpusId": 253267506, "publicationVenue": {"id": "e89b8f81-f9cd-4d2a-ab62-905167b1b2df", + "name": "Molecular Cancer Research", "type": "journal", "alternate_names": + ["Mol Cancer Res"], "issn": "1541-7786", "url": "https://mcr.aacrjournals.org/", + "alternate_urls": ["http://mcr.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/1e1722c24354818457609a4a04df2345237045b3", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Molecular Cancer Research", "year": + 2022, "referenceCount": 1, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Education", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-11-03", "journal": {"volume": "20 11", "pages": "\n 1591-1597\n ", + "name": "Molecular cancer research : MCR"}, "authors": [{"authorId": "2178880764", + "name": "Kenneth C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2149691856", "name": "Riccardo Dalla-Favera"}, {"authorId": + "2059177512", "name": "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis + A Diaz"}, {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": "145213930", + "name": "K. Flaherty"}, {"authorId": "2069169888", "name": "Philip D. Greenberg"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "3286001", "name": + "E. Mardis"}, {"authorId": "4008854", "name": "E. Platz"}, {"authorId": "2059212154", + "name": "M. N. Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, + {"authorId": "2469902", "name": "L. Siu"}, {"authorId": "5866492", "name": + "B. Teicher"}]}, {"paperId": "24f56eedec56a97712d17808ebdd4a50f6107475", "externalIds": + {"DOI": "10.1038/s41571-022-00611-7", "CorpusId": 246946213, "PubMed": "35181748"}, + "corpusId": 246946213, "publicationVenue": {"id": "e665d258-d079-4464-9b33-2291ffb17a14", + "name": "Nature Reviews Clinical Oncology", "type": "journal", "alternate_names": + ["Nat Rev Clin Oncol"], "issn": "1759-4774", "url": "http://www.nature.com/nrclinonc/", + "alternate_urls": ["http://www.nature.com/nrclinonc", "http://www.nature.com/nrclinonc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/24f56eedec56a97712d17808ebdd4a50f6107475", + "title": "Author Correction: Radiotherapy as a tool to elicit clinically actionable + signalling pathways in cancer", "abstract": null, "venue": "Nature Reviews + Clinical Oncology", "year": 2022, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/s41571-022-00611-7.pdf", "status": null}, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["Review"], "publicationDate": "2022-02-18", "journal": + {"volume": "19", "pages": "281", "name": "Nature Reviews Clinical Oncology"}, + "authors": [{"authorId": "21711615", "name": "G. Petroni"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4204823", "name": "L. Santambrogio"}, + {"authorId": "145423973", "name": "S. Formenti"}, {"authorId": "3974364", + "name": "L. Galluzzi"}]}, {"paperId": "2a616128b7d77e2a246ed3f0b9f7f6a45c08211a", + "externalIds": {"PubMedCentral": "9436778", "DOI": "10.1038/s41430-022-01179-2", + "CorpusId": 251108431, "PubMed": "35896818"}, "corpusId": 251108431, "publicationVenue": + {"id": "68d9e7c1-01cc-4bd0-a6c7-8c976e44b931", "name": "European Journal of + Clinical Nutrition", "type": "journal", "alternate_names": ["Eur J Clin Nutr"], + "issn": "0954-3007", "url": "https://www.nature.com/ejcn/", "alternate_urls": + ["http://www.naturesj.com/ejcn/index.html", "http://www.nature.com/ejcn/index.html"]}, + "url": "https://www.semanticscholar.org/paper/2a616128b7d77e2a246ed3f0b9f7f6a45c08211a", + "title": "Competing paradigms of obesity pathogenesis: energy balance versus + carbohydrate-insulin models", "abstract": null, "venue": "European Journal + of Clinical Nutrition", "year": 2022, "referenceCount": 243, "citationCount": + 9, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/s41430-022-01179-2.pdf", "status": null}, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "2022-07-28", + "journal": {"volume": "76", "pages": "1209 - 1221", "name": "European Journal + of Clinical Nutrition"}, "authors": [{"authorId": "2137680835", "name": "D. + S. Ludwig"}, {"authorId": "6767830", "name": "C. Apovian"}, {"authorId": "4471209", + "name": "L. Aronne"}, {"authorId": "47518061", "name": "A. Astrup"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4056154", "name": "C. Ebbeling"}, + {"authorId": "1703514", "name": "S. Heymsfield"}, {"authorId": "143913880", + "name": "James D. Johnson"}, {"authorId": "1756443", "name": "J. King"}, {"authorId": + "2106276088", "name": "R. Krauss"}, {"authorId": "2179345988", "name": "Gary + Taubes"}, {"authorId": "2054653160", "name": "J. Volek"}, {"authorId": "47270053", + "name": "E. Westman"}, {"authorId": "2132591752", "name": "W. Willett"}, {"authorId": + "41183477", "name": "W. Yancy"}, {"authorId": "143673144", "name": "M. Friedman"}]}, + {"paperId": "34562411fc5cc3303c13197c5c70b9e309a6651f", "externalIds": {"DOI": + "10.1158/1078-0432.CCR-22-3167", "CorpusId": 253245912, "PubMed": "36317374"}, + "corpusId": 253245912, "publicationVenue": {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", + "name": "Clinical Cancer Research", "type": "journal", "alternate_names": + ["Clin Cancer Res"], "issn": "1078-0432", "url": "https://clincancerres.aacrjournals.org/", + "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/34562411fc5cc3303c13197c5c70b9e309a6651f", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Clinical Cancer Research", "year": + 2022, "referenceCount": 1, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Education", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-11-01", "journal": {"volume": "28 21", "pages": "\n 4593-4599\n ", + "name": "Clinical cancer research : an official journal of the American Association + for Cancer Research"}, "authors": [{"authorId": "2178880764", "name": "Kenneth + C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1396265158", "name": "R. Dalla-Favera"}, {"authorId": "2059177512", "name": + "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis A Diaz"}, {"authorId": + "4135978", "name": "R. DuBois"}, {"authorId": "145213930", "name": "K. Flaherty"}, + {"authorId": "2069169888", "name": "Philip D. Greenberg"}, {"authorId": "6213932", + "name": "M. Loda"}, {"authorId": "3286001", "name": "E. Mardis"}, {"authorId": + "4008854", "name": "E. Platz"}, {"authorId": "2059212154", "name": "M. N. + Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, {"authorId": "2469902", + "name": "L. Siu"}, {"authorId": "5866492", "name": "B. Teicher"}]}, {"paperId": + "414c0a65ce84112ee418944c0e8f7022b745146c", "externalIds": {"PubMedCentral": + "9753996", "DOI": "10.1182/blood-2021-153378", "CorpusId": 244535280, "PubMed": + "36282572"}, "corpusId": 244535280, "publicationVenue": {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", + "name": "Journal of Clinical Investigation", "type": "journal", "alternate_names": + ["J Clin Investig"], "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": + ["http://www.jci.org/", "https://www.jci.org/archive", "http://www.jci.org/impact"]}, + "url": "https://www.semanticscholar.org/paper/414c0a65ce84112ee418944c0e8f7022b745146c", + "title": "A FOXO1-dependent transcription network is a targetable vulnerability + of mantle cell lymphomas", "abstract": "Targeting lineage-defined transcriptional + dependencies has emerged as an effective therapeutic strategy in cancer treatment. + Through screening for molecular vulnerabilities of mantle cell lymphoma (MCL), + we identified a set of transcription factors (TFs) including FOXO1, EBF1, + PAX5, and IRF4 that are essential for MCL propagation. Integrated chromatin + immunoprecipitation and sequencing (ChIP-Seq) with transcriptional network + reconstruction analysis revealed FOXO1 as a master regulator that acts upstream + in the regulatory TF hierarchy. FOXO1 is both necessary and sufficient to + drive MCL lineage commitment through supporting the lineage-specific transcription + programs. We further show that FOXO1, but not its close paralog FOXO3, can + reprogram myeloid leukemia cells and induce B-lineage gene expression. Finally, + we demonstrate that cpd10, a small molecule identified from an enriched FOXO1 + inhibitor library, induces a robust cytotoxic response in MCL cells in vitro + and suppresses MCL progression in vivo. Our findings establish FOXO1 inhibition + as a therapeutic strategy targeting lineage-driven transcriptional addiction + in MCL.", "venue": "Journal of Clinical Investigation", "year": 2021, "referenceCount": + 79, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2021-11-05", "journal": + {"volume": "132", "name": "The Journal of Clinical Investigation"}, "authors": + [{"authorId": "6134501", "name": "Ja-Young Jang"}, {"authorId": "40169754", + "name": "I. Hwang"}, {"authorId": "47837375", "name": "H. Pan"}, {"authorId": + "144027014", "name": "Jun Yao"}, {"authorId": "6401197", "name": "L. Alinari"}, + {"authorId": "7461456", "name": "E. Imada"}, {"authorId": "2081531809", "name": + "Claudio Zanettini"}, {"authorId": "5833490", "name": "M. Kluk"}, {"authorId": + "47905638", "name": "Yizhe Wang"}, {"authorId": "7856471", "name": "Yun-Kyoung + Lee"}, {"authorId": "40496262", "name": "Hua V. Lin"}, {"authorId": "22172195", + "name": "Xiangao Huang"}, {"authorId": "5174216", "name": "M. Di Liberto"}, + {"authorId": "49864822", "name": "Zhengming Chen"}, {"authorId": "8914112", + "name": "K. Ballman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2479350", "name": "L. Marchionni"}, {"authorId": "2536360", "name": "G. Inghirami"}, + {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": "5097073", + "name": "R. Baiocchi"}, {"authorId": "1398158850", "name": "S. Chen\u2010Kiang"}, + {"authorId": "48738953", "name": "S. Belvedere"}, {"authorId": "145735876", + "name": "Hongwu Zheng"}, {"authorId": "2136475667", "name": "J. Paik"}]}, + {"paperId": "48155eae59bfbb67b6621bea1351bba745b50d3d", "externalIds": {"DOI": + "10.1038/s41422-022-00723-w", "CorpusId": 252181567, "PubMed": "36085369"}, + "corpusId": 252181567, "publicationVenue": {"id": "45c77f4e-d4c0-4df3-99dd-119b0d2adb78", + "name": "Cell Research", "type": "journal", "alternate_names": ["Cell Res"], + "issn": "1001-0602", "url": "http://www.cell-research.com/", "alternate_urls": + ["http://www.cell-research.com/index.asp", "http://www.nature.com/cr/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/48155eae59bfbb67b6621bea1351bba745b50d3d", + "title": "Live cold to grow old? Thermogenesis to fight cancer", "abstract": + null, "venue": "Cell Research", "year": 2022, "referenceCount": 11, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/s41422-022-00723-w.pdf", "status": null}, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2022-09-09", "journal": + {"volume": "32", "pages": "1042 - 1043", "name": "Cell Research"}, "authors": + [{"authorId": "38751542", "name": "H. Langer"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "145524334", "name": "M. Goncalves"}]}, {"paperId": + "49596b7d8df1ad22a4e0c723dde9fff5baa8fd11", "externalIds": {"PubMedCentral": + "9352595", "DOI": "10.1038/s41586-022-04984-8", "CorpusId": 251133354, "PubMed": + "35896750"}, "corpusId": 251133354, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/49596b7d8df1ad22a4e0c723dde9fff5baa8fd11", + "title": "PI3K drives the de novo synthesis of coenzyme A from vitamin B5", + "abstract": null, "venue": "Nature", "year": 2022, "referenceCount": 87, "citationCount": + 8, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/s41586-022-04984-8.pdf", "status": null}, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2022-07-27", "journal": + {"volume": "608", "pages": "192 - 198", "name": "Nature"}, "authors": [{"authorId": + "7449887", "name": "Christian C. Dibble"}, {"authorId": "2096849703", "name": + "S. Barritt"}, {"authorId": "2179440798", "name": "Grace E Perry"}, {"authorId": + "4729701", "name": "Evan C. Lien"}, {"authorId": "13850298", "name": "Renee + C. Geck"}, {"authorId": "2179439798", "name": "Sarah E DuBois-Coyne"}, {"authorId": + "8023165", "name": "David Bartee"}, {"authorId": "13474796", "name": "Thomas + T. Zengeya"}, {"authorId": "49273595", "name": "Emily B. Cohen"}, {"authorId": + "49059923", "name": "M. Yuan"}, {"authorId": "48821307", "name": "B. Hopkins"}, + {"authorId": "6033148", "name": "J. Meier"}, {"authorId": "4102988", "name": + "J. Clohessy"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "145751285", "name": "A. Toker"}]}, + {"paperId": "4e01cd4e5ee73cda411ec541b60c46df1bfd912f", "externalIds": {"DOI": + "10.1101/2022.07.19.500601", "CorpusId": 250945722}, "corpusId": 250945722, + "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": + "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/4e01cd4e5ee73cda411ec541b60c46df1bfd912f", + "title": "Epinephrine inhibits PI3K alpha via the Hippo kinases", "abstract": + "The phosphoinositide 3-kinase, p110\u03b1, is an essential mediator of insulin + signaling and glucose homeostasis. We systematically interrogated the human + serine, threonine, and tyrosine kinome to search for novel regulators of p110\u03b1 + and found that the Hippo kinases phosphorylate and completely inhibit its + activity. This inhibitory state corresponds to a conformational change of + a membrane binding domain on p110\u03b1, which impairs its ability to engage + membranes. In human primary hepatocytes, cancer cell lines, and rodent tissues, + activation of the Hippo kinases, MST1/2, using forskolin or epinephrine is + associated with phosphorylation and inhibition of p110\u03b1, impairment of + downstream insulin signaling, and suppression of glycolysis and glycogen synthesis. + These changes are abrogated when MST1/2 are genetically deleted or inhibited + with small molecules. Our study reveals a novel inhibitory pathway of PI3K + signaling and a previously unappreciated link between epinephrine and insulin + signaling.", "venue": "bioRxiv", "year": 2022, "referenceCount": 7, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.biorxiv.org/content/biorxiv/early/2022/07/20/2022.07.19.500601.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2022-07-20", "journal": {"name": "bioRxiv"}, "authors": + [{"authorId": "144181325", "name": "Ting-Yu Lin"}, {"authorId": "2058412873", + "name": "Shakti Ramsamooj"}, {"authorId": "51910553", "name": "Katarina M + Liberatore"}, {"authorId": "4238131", "name": "L. Lantier"}, {"authorId": + "35123724", "name": "N. Vasan"}, {"authorId": "3662293", "name": "Kannan R. + Karukurichi"}, {"authorId": "4151944", "name": "Seo-Kyoung Hwang"}, {"authorId": + "4354461", "name": "E. Kesicki"}, {"authorId": "4306515", "name": "Edward + R. Kastenhuber"}, {"authorId": "47847765", "name": "T. Wiederhold"}, {"authorId": + "5247030", "name": "Tomer M. Yaron"}, {"authorId": "2178292087", "name": "Mengmeng + Zhu"}, {"authorId": "50032234", "name": "Yilun Ma"}, {"authorId": "4422893", + "name": "M. Paddock"}, {"authorId": "49288368", "name": "Guoan Zhang"}, {"authorId": + "48821307", "name": "B. Hopkins"}, {"authorId": "3532500", "name": "O. McGuinness"}, + {"authorId": "46462360", "name": "R. Schwartz"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "145524334", "name": "M. Goncalves"}]}, {"paperId": "50a1043090a989516643c64c2f6734f1a837920f", + "externalIds": {"DOI": "10.1002/ana.22667", "CorpusId": 221444009, "PubMed": + "35387712"}, "corpusId": 221444009, "publicationVenue": {"id": "459ca45a-35b5-468b-8287-daffcd7d5acc", + "name": "Aerospace Medicine and Human Performance", "type": "journal", "alternate_names": + ["Aerosp Med Hum Perform", "Aerospace medicine and human performance", "Aerosp + med hum perform"], "issn": "2375-6314", "url": "http://www.asma.org/journal/", + "alternate_urls": ["https://www.asma.org/journal/asem-journal"]}, "url": "https://www.semanticscholar.org/paper/50a1043090a989516643c64c2f6734f1a837920f", + "title": "Program at a Glance", "abstract": "09:10 Neurocognitive functioning, + physical health, and mental health of school-aged children treated with propranolol + or atenolol for infantile hemangioma \u2502 Mireille M. Hermans, Andr\u00e9 + B. Rietman*, Renske Schappin*, Peter C.J. de Laat, Elodie J. Mendels, Johannes + M.P.J. Breur, Hester R. Langeveld, Saskia N. de Wildt, Corstiaan C. Breugem, + Marlies de Graaf, Martine F. Raphael and Suzanne G.M.A. Pasmans", "venue": + "Aerospace Medicine and Human Performance", "year": 2022, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://ieeexplore.ieee.org/ielx7/9252189/9252106/09252519.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-03-01", "journal": {"volume": "68", "name": "Annals + of Neurology"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2168559185", "name": "Alain Borzuck"}, {"authorId": "3484984", + "name": "M. Baad"}, {"authorId": "83543026", "name": "Bradley Pua"}, {"authorId": + "144868826", "name": "Catherine McGuinn"}, {"authorId": "2168582898", "name": + "B. Alicia"}, {"authorId": "2168583690", "name": "Byrne"}, {"authorId": "5421966", + "name": "P. Brouillard"}, {"authorId": "48836291", "name": "Drew L. Sutton"}, + {"authorId": "2426324", "name": "J. Kazenwadel"}, {"authorId": "2156959511", + "name": "Saba Montazaribarforoushi"}, {"authorId": "2168586509", "name": "Genevieve"}, + {"authorId": "31907057", "name": "A. Secker"}, {"authorId": "6908369", "name": + "Anna Oszmiana"}, {"authorId": "38707585", "name": "M. Babic"}, {"authorId": + "4153047", "name": "Kelly L. Betterman"}, {"authorId": "4091304", "name": + "P. Brautigan"}, {"authorId": "2168560346", "name": "Melissa White"}, {"authorId": + "38283641", "name": "Sandra G. Piltz"}, {"authorId": "2168595173", "name": + "Paul Q. Thomas"}, {"authorId": "144901007", "name": "C. Hahn"}, {"authorId": + "123915070", "name": "M. Rath"}, {"authorId": "4947542", "name": "U. Felbor"}, + {"authorId": "116839082", "name": "G. Christoph"}, {"authorId": "2168583530", + "name": "Korenke"}, {"authorId": "2116358139", "name": "Christopher Smith"}, + {"authorId": "32207073", "name": "Kathleen H. Wood"}, {"authorId": "49468008", + "name": "Sarah E. Sheppard"}, {"authorId": "2069620315", "name": "D. Adams"}, + {"authorId": "2079389462", "name": "Ariana"}, {"authorId": "2168585568", "name": + "Kariminejad"}, {"authorId": "2956409", "name": "R. Helaers"}, {"authorId": + "6863639", "name": "L. Boon"}, {"authorId": "3566073", "name": "N. Revencu"}, + {"authorId": "38111488", "name": "L. Moore"}, {"authorId": "2164838138", "name": + "Christopher"}, {"authorId": "2082310484", "name": "Barnett"}, {"authorId": + "4728850", "name": "E. Haan"}, {"authorId": "3640552", "name": "M. Vikkula"}, + {"authorId": "1966722", "name": "H. Scott"}, {"authorId": "4547684", "name": + "N. Harvey"}, {"authorId": "1391226977", "name": "Kaitlyn"}, {"authorId": + "2168575234", "name": "Zenner"}, {"authorId": "22696955", "name": "V. Dmyterko"}, + {"authorId": "50004404", "name": "S. Ganti"}, {"authorId": "2052967731", "name": + "T. James"}, {"authorId": "2168586017", "name": "Bennett"}, {"authorId": "115868571", + "name": "C. Shawber"}, {"authorId": "122815850", "name": "Michael W. Dellinger"}, + {"authorId": "3421588", "name": "L. Guibaud"}]}, {"paperId": "563beccd56c46533238cdcc1b97e45cc50b5e5c2", + "externalIds": {"DOI": "10.1158/1078-0432.CCR-21-3045", "CorpusId": 246776268, + "PubMed": "35149538"}, "corpusId": 246776268, "publicationVenue": {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", + "name": "Clinical Cancer Research", "type": "journal", "alternate_names": + ["Clin Cancer Res"], "issn": "1078-0432", "url": "https://clincancerres.aacrjournals.org/", + "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/563beccd56c46533238cdcc1b97e45cc50b5e5c2", + "title": "Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients + with Advanced Triple-Negative Breast Cancer.", "abstract": "PURPOSE\nWe had + previously reported on the safety and the recommended phase 2 dose (RP2D) + of olaparib in combination with the PI3K\u03b1-specific inhibitor alpelisib + in patients with high-grade serous ovarian cancer as studied in a phase 1b + trial (NCT01623349). Here we report on the breast cancer cohort from that + study.\n\n\nEXPERIMENTAL DESIGN\nEligible patients had recurrent triple-negative + breast cancer (TNBC), or recurrent breast cancer of any subtype with a germline + BRCA mutation and were enrolled to a dose escalation or expansion cohort. + After definition of the RP2D, secondary end points included safety and objective + response rate (ORR). Exploratory analyses were performed using circulating + free DNA (cfDNA).\n\n\nRESULTS\n17 patients with TNBC were enrolled with a + median of 3 prior lines of chemotherapy. The most common treatment-related + grade 3-4 adverse events were hyperglycemia (18%) and rash (12%). The ORR + was 18% (23% for patients treated at the RP2D) and 59% had disease control. + The median duration of response was 7.4 months. Analysis of cfDNA tumor fractions + (TFx) revealed that patients with TFx<15% after completion of the first cycle + had a longer progression-free survival compared to those with TFx>15% (6.0 + months vs 0.9 months, p=0.0001).\n\n\nCONCLUSIONS\nAlpelisib in combination + with olaparib is tolerable in patients with pre-treated TNBC, with evidence + of activity in non-BRCA carriers. CfDNA provided important prognostic information. + Results highlight potential synergistic use of a PI3Ki to sensitize HR-proficient + (BRCA wild-type) TNBC to PARPi and suggest the potential to expand the use + of PARPi beyond BRCA-mutant tumors.", "venue": "Clinical Cancer Research", + "year": 2022, "referenceCount": 0, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2022-02-11", "journal": + {"name": "Clinical cancer research : an official journal of the American Association + for Cancer Research"}, "authors": [{"authorId": "6936023", "name": "Felipe + Batalini"}, {"authorId": "1867565334", "name": "N. Xiong"}, {"authorId": "4518265", + "name": "N. Tayob"}, {"authorId": "51160410", "name": "Madeline Polak"}, {"authorId": + "27883005", "name": "J. Eismann"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2014583", "name": "G. Shapiro"}, {"authorId": "4298787", "name": + "V. Adalsteinsson"}, {"authorId": "2369378", "name": "E. Winer"}, {"authorId": + "49610180", "name": "P. Konstantinopoulos"}, {"authorId": "1396108662", "name": + "A. D\u2019Andrea"}, {"authorId": "3733822", "name": "E. Swisher"}, {"authorId": + "6927295", "name": "U. Matulonis"}, {"authorId": "31554501", "name": "G. Wulf"}, + {"authorId": "3349811", "name": "E. Mayer"}]}, {"paperId": "5a41a6716e9d75f4c08cd32a4f9c4afc43c96642", + "externalIds": {"DOI": "10.1158/0008-5472.CAN-22-2453", "CorpusId": 253258327, + "PubMed": "36321264"}, "corpusId": 253258327, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/5a41a6716e9d75f4c08cd32a4f9c4afc43c96642", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Cancer Research", "year": 2022, "referenceCount": + 1, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Education", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2022-11-02", "journal": + {"volume": "82 21", "pages": "\n 3861-3867\n ", "name": "Cancer + research"}, "authors": [{"authorId": "2178880764", "name": "Kenneth C. Anderson"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1396265158", + "name": "R. Dalla-Favera"}, {"authorId": "2059177512", "name": "C. V. Dang"}, + {"authorId": "2189433262", "name": "Luis A Diaz"}, {"authorId": "4135978", + "name": "R. DuBois"}, {"authorId": "145213930", "name": "K. Flaherty"}, {"authorId": + "2069169888", "name": "Philip D. Greenberg"}, {"authorId": "6213932", "name": + "M. Loda"}, {"authorId": "3286001", "name": "E. Mardis"}, {"authorId": "4008854", + "name": "E. Platz"}, {"authorId": "2059212154", "name": "M. N. Pollak"}, {"authorId": + "39884192", "name": "R. Schreiber"}, {"authorId": "2469902", "name": "L. Siu"}, + {"authorId": "5866492", "name": "B. Teicher"}]}, {"paperId": "696a7d9d25ef420b7724adbca60a3fa8dd82917e", + "externalIds": {"PubMedCentral": "9360437", "DOI": "10.1038/s41467-022-32135-0", + "CorpusId": 251444738, "PubMed": "35941104"}, "corpusId": 251444738, "publicationVenue": + {"id": "43b3f0f9-489a-4566-8164-02fafde3cd98", "name": "Nature Communications", + "type": "journal", "alternate_names": ["Nat Commun"], "issn": "2041-1723", + "url": "https://www.nature.com/ncomms/", "alternate_urls": ["http://www.nature.com/ncomms/about/index.html", + "http://www.nature.com/ncomms/index.html"]}, "url": "https://www.semanticscholar.org/paper/696a7d9d25ef420b7724adbca60a3fa8dd82917e", + "title": "Blocking ActRIIB and restoring appetite reverses cachexia and improves + survival in mice with lung cancer", "abstract": null, "venue": "Nature Communications", + "year": 2022, "referenceCount": 83, "citationCount": 3, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/s41467-022-32135-0.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-08-08", "journal": {"volume": "13", "name": "Nature + Communications"}, "authors": [{"authorId": "7706581", "name": "Andr\u00c9 + L Queiroz"}, {"authorId": "2180926194", "name": "Ezequiel Dantas"}, {"authorId": + "2058412873", "name": "Shakti Ramsamooj"}, {"authorId": "2087916646", "name": + "Anirudh Murthy"}, {"authorId": "2181973235", "name": "Mujmmail Ahmed"}, {"authorId": + "25057716", "name": "E. Zunica"}, {"authorId": "46875693", "name": "R. Liang"}, + {"authorId": "2180811849", "name": "Jessica Murphy"}, {"authorId": "46415060", + "name": "Corey D. Holman"}, {"authorId": "34685572", "name": "Curtis J. Bare"}, + {"authorId": "2126874550", "name": "G. Ghahramani"}, {"authorId": "2385505", + "name": "Zhidan Wu"}, {"authorId": "144647984", "name": "D. Cohen"}, {"authorId": + "4881087", "name": "J. Kirwan"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "51224707", "name": "C. Axelrod"}, {"authorId": "145524334", + "name": "M. Goncalves"}]}, {"paperId": "750d2117770a3746fd79bda769aa32436401815a", + "externalIds": {"DOI": "10.1093/ajcn/nqab385", "CorpusId": 246700740, "PubMed": + "35139162"}, "corpusId": 246700740, "publicationVenue": {"id": "52460d26-e705-465a-b49c-92bb07e81ee0", + "name": "American Journal of Clinical Nutrition", "type": "journal", "alternate_names": + ["The American Journal of Clinical Nutrition", "Am J Clin Nutr"], "issn": + "0002-9165", "url": "http://www.ajcn.org/"}, "url": "https://www.semanticscholar.org/paper/750d2117770a3746fd79bda769aa32436401815a", + "title": "Reply to A Drewnowski et al, O Devinsky, D A Booth and E L Gibson, + and D J Millward.", "abstract": null, "venue": "American Journal of Clinical + Nutrition", "year": 2022, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://academic.oup.com/ajcn/article-pdf/115/2/595/43337594/nqab385.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-02-09", "journal": {"volume": "115 2", "pages": "\n 595-597\n ", + "name": "The American journal of clinical nutrition"}, "authors": [{"authorId": + "2137680835", "name": "D. 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Ebbeling"}]}, {"paperId": "761964f2f25dfe76d67d9da0f80025e487710d94", + "externalIds": {"DOI": "10.1016/j.cub.2022.01.027", "CorpusId": 246638820, + "PubMed": "35134350"}, "corpusId": 246638820, "publicationVenue": {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", + "name": "Current Biology", "type": "journal", "alternate_names": ["Curr Biology"], + "issn": "0960-9822", "url": "http://www.current-biology.com/", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/09609822"]}, "url": "https://www.semanticscholar.org/paper/761964f2f25dfe76d67d9da0f80025e487710d94", + "title": "Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, + Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward + Rheb", "abstract": null, "venue": "Current Biology", "year": 2022, "referenceCount": + 0, "citationCount": 3, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S0960982222000380/pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}], "publicationTypes": null, "publicationDate": + "2022-02-01", "journal": {"volume": "32", "pages": "733-734", "name": "Current + Biology"}, "authors": [{"authorId": "3870554", "name": "A. Tee"}, {"authorId": + "2339651", "name": "B. Manning"}, {"authorId": "1718769", "name": "Philippe + P Roux"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4037343", + "name": "J. Blenis"}]}, {"paperId": "8152ae775c54f372297d18357ffe24efbe244c3f", + "externalIds": {"DOI": "10.1038/s41568-022-00485-y", "CorpusId": 249065532, + "PubMed": "35614234"}, "corpusId": 249065532, "publicationVenue": {"id": "db36cc4c-07df-41a8-9169-9ace7e520923", + "name": "Nature Reviews. Cancer", "type": "journal", "alternate_names": ["Nature + Reviews Cancer", "Nat Rev Cancer"], "issn": "1474-175X", "url": "https://www.nature.com/nrc/", + "alternate_urls": ["http://www.nature.com/nrc/index.html"]}, "url": "https://www.semanticscholar.org/paper/8152ae775c54f372297d18357ffe24efbe244c3f", + "title": "Developing dietary interventions as therapy for cancer.", "abstract": + null, "venue": "Nature Reviews. 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Goncalves"}]}, + {"paperId": "83a97a9787e65494bc50105484adfda6ae10e7e2", "externalIds": {"PubMedCentral": + "9050834", "DOI": "10.1038/s42255-022-00553-5", "CorpusId": 247855394, "PubMed": + "35361954"}, "corpusId": 247855394, "publicationVenue": {"id": "f8dd1b61-789d-48ec-b550-a6245826a9aa", + "name": "Nature Metabolism", "alternate_names": ["Nat Metab"], "issn": "2522-5812", + "url": "https://www.nature.com/natmetab/"}, "url": "https://www.semanticscholar.org/paper/83a97a9787e65494bc50105484adfda6ae10e7e2", + "title": "Altered propionate metabolism contributes to tumor progression and + aggressiveness", "abstract": null, "venue": "Nature Metabolism", "year": 2022, + "referenceCount": 21, "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2022-03-18", "journal": {"volume": "4", "pages": "435 - 443", "name": "Nature + metabolism"}, "authors": [{"authorId": "2087116099", "name": "Ana P Gomes"}, + {"authorId": "3324022", "name": "Didem Ilter"}, {"authorId": "121128193", + "name": "V. Low"}, {"authorId": "13926786", "name": "S. Dr\u00e1pela"}, {"authorId": + "50356549", "name": "Tanya Schild"}, {"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "1886508939", "name": "Julie Han"}, {"authorId": + "2382021", "name": "Ilaria Elia"}, {"authorId": "11236293", "name": "D. Broekaert"}, + {"authorId": "1887417083", "name": "A. Rosenzweig"}, {"authorId": "37644389", + "name": "Michal J. Nagiec"}, {"authorId": "49872748", "name": "Joana B Nunes"}, + {"authorId": "31358846", "name": "B. Schaffer"}, {"authorId": "5135907", "name": + "A. Mutvei"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "46775302", "name": "S. Fendt"}, {"authorId": + "4037343", "name": "J. Blenis"}]}, {"paperId": "83b7dc1d3c010b7473aecf1b33c1a2596ddd5b0b", + "externalIds": {"DOI": "10.1158/1940-6207.CAPR-22-0369", "CorpusId": 253246166, + "PubMed": "36317369"}, "corpusId": 253246166, "publicationVenue": {"id": "30248bd8-0140-4a2a-b2f7-d817cf173fdd", + "name": "Cancer Prevention Research", "type": "journal", "alternate_names": + ["Cancer Prev Res"], "issn": "1940-6215", "url": "https://cancerpreventionresearch.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/83b7dc1d3c010b7473aecf1b33c1a2596ddd5b0b", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Cancer Prevention Research", "year": + 2022, "referenceCount": 1, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Education", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-11-01", "journal": {"volume": "15 11", "pages": "\n 705-712\n ", + "name": "Cancer prevention research"}, "authors": [{"authorId": "2178880764", + "name": "Kenneth C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1396265158", "name": "R. Dalla-Favera"}, {"authorId": "2059177512", + "name": "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis A Diaz"}, + {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": "145213930", "name": + "K. Flaherty"}, {"authorId": "2069169888", "name": "Philip D. Greenberg"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "3286001", "name": + "E. Mardis"}, {"authorId": "4008854", "name": "E. Platz"}, {"authorId": "2059212154", + "name": "M. N. Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, + {"authorId": "2469902", "name": "L. Siu"}, {"authorId": "5866492", "name": + "B. Teicher"}]}, {"paperId": "99d2a19bc372400eb229907e964c25cfaabdc71b", "externalIds": + {"DOI": "10.1158/1055-9965.EPI-22-0852", "CorpusId": 253258253, "PubMed": + "36321301"}, "corpusId": 253258253, "publicationVenue": {"id": "9888b440-2c06-477b-9a8a-d051b0287fbc", + "name": "Cancer Epidemiology, Biomarkers and Prevention", "type": "journal", + "alternate_names": ["Cancer Epidemiology, Biomarkers & Prevention", "Cancer + Epidemiology Biomarkers Prev", "Cancer Epidemiology Biomarkers Prev"], "issn": + "1055-9965", "url": "https://cebp.aacrjournals.org/", "alternate_urls": ["http://cebp.aacrjournals.org//"]}, + "url": "https://www.semanticscholar.org/paper/99d2a19bc372400eb229907e964c25cfaabdc71b", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Cancer Epidemiology, Biomarkers and + Prevention", "year": 2022, "referenceCount": 1, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Education", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-11-02", "journal": {"volume": "31 11", "pages": "\n 1995-2001\n ", + "name": "Cancer epidemiology, biomarkers & prevention : a publication of the + American Association for Cancer Research, cosponsored by the American Society + of Preventive Oncology"}, "authors": [{"authorId": "2178880764", "name": "Kenneth + C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2149691856", "name": "Riccardo Dalla-Favera"}, {"authorId": "2059177512", + "name": "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis A Diaz"}, + {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": "145213930", "name": + "K. Flaherty"}, {"authorId": "2069169888", "name": "Philip D. Greenberg"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "3286001", "name": + "E. Mardis"}, {"authorId": "4008854", "name": "E. Platz"}, {"authorId": "2059212154", + "name": "M. N. Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, + {"authorId": "2469902", "name": "L. Siu"}, {"authorId": "5866492", "name": + "B. Teicher"}]}, {"paperId": "a6c37d54638b52049bd75c1db63b57c625563b33", "externalIds": + {"DOI": "10.1200/jco.2022.40.16_suppl.tps1113", "CorpusId": 249450778}, "corpusId": + 249450778, "publicationVenue": {"id": "a5913268-3957-484f-b41f-347b0ba23338", + "name": "Journal of Clinical Oncology", "type": "journal", "alternate_names": + ["J Clin Oncol"], "issn": "0732-183X", "url": "https://ascopubs.org/loi/jco", + "alternate_urls": ["http://www.jco.org/", "http://jco.ascopubs.org/"]}, "url": + "https://www.semanticscholar.org/paper/a6c37d54638b52049bd75c1db63b57c625563b33", + "title": "Targeting insulin feedback to enhance alpelisib (TIFA): A phase + II randomized trial in metastatic, PIK3CA-mutant, hormone receptor\u2013positive + breast cancer.", "abstract": "TPS1113 Background: Breast cancer is the most + common malignancy among women in the U.S. and is a leading cause of cancer-related + death. Among women with hormone receptor (HR)-positive, human epidermal growth + factor receptor 2 (HER2)-negative breast cancer, 45% harbor activating mutations + in the PIK3CA gene , which induces hyperactivation of phosphatidylinositol + 3-kinase (PI3K) and drives cell growth and survival. The SOLAR-1 trial found + that the combination of alpelisib, a PI3K inhibitor, and fulvestrant, an endocrine + therapy, significantly improved progression-free survival compared to fulvestrant + alone, leading to Food and Drug Administration approval in PIK3CA-mutated + metastatic breast cancer. While PI3K inhibition induces apoptosis of cancer + cells, inhibition of this pathway in the liver and skeletal muscle impairs + physiologic insulin signaling leading to hyperglycemia. This affects > 60% + of patients, results in grade 3-4 hyperglycemia in 36% of patients, and is + a major cause of interrupted/reduced dosing or discontinuation. In preclinical + models, application of a very low carbohydrate (ketogenic) diet or a sodium-glucose + cotransporter 2 inhibitor (SGLT2i), a commonly used diabetes medication, minimized + hyperglycemia and improved the anti-tumor efficacy of PI3K inhibition. These + interventions are safe and feasible in cancer patients but have not been studied + for the prevention of PI3K inhibitor-associated hyperglycemia. Methods: We + are conducting a multicenter phase II clinical trial (NCT05090358) in patients + receiving standard-of-care alpelisib plus fulvestrant to test the efficacy + of three interventions (n = 106): 1) ketogenic diet, 2) low-carbohydrate diet, + or 3) canagliflozin (a SGLT2i) in preventing alpelisib-associated hyperglycemia. + The goal of this study is to mitigate a major toxicity of PI3K inhibitors + and maximize their clinical efficacy. Eligible patients must be postmenopausal + and have histologically confirmed HR-positive, HER2-negative metastatic breast + cancer, \u22651 activating PIK3CA mutations, measurable disease per RECIST + v1.1 or at least one predominantly lytic bone lesion, recurrence or progression + during or after endocrine-based therapy, ECOG performance status of 0-1, hemoglobin + A1c < 8%, and fasting blood glucose < = 140mg/dL. Prior CDK4/6 inhibitor use + is allowed. The primary endpoint is the grade 3-4 hyperglycemia-free rate + at 12 weeks. Secondary endpoints include the 6- and 12-month overall response + rate, 6- and 12-month progression-free survival, alpelisib adherence, changes + in systemic hormones and metabolites related to glucose homeostasis, changes + in body composition, and quality of life. The first patient was enrolled on + October 15, 2021. Participating sites include Memorial Sloan Kettering Cancer + Center, Weill Cornell Medical Center, and the Ohio State University Wexner + Medical Center. Clinical trial information: NCT05090358.", "venue": "Journal + of Clinical Oncology", "year": 2022, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Medicine", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2022-06-01", "journal": {"name": + "Journal of Clinical Oncology"}, "authors": [{"authorId": "1988901845", "name": + "S. Shen"}, {"authorId": "83272213", "name": "Erica Salehi"}, {"authorId": + "4116933", "name": "A. Farooki"}, {"authorId": "5472574", "name": "J. Flory"}, + {"authorId": "2168765454", "name": "Dominiq Williams"}, {"authorId": "2158283600", + "name": "A. Carpio"}, {"authorId": "2157872668", "name": "Cassandra Chang"}, + {"authorId": "2397510", "name": "M. Lacouture"}, {"authorId": "5685899", "name": + "E. Andreopoulou"}, {"authorId": "14626356", "name": "S. Sardesai"}, {"authorId": + "47352468", "name": "K. Jhaveri"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "145524334", "name": "M. Goncalves"}, {"authorId": "4018492", + "name": "N. Iyengar"}]}, {"paperId": "a878a8e06a3770e4c23a9304e5daa6150bb9fd91", + "externalIds": {"DOI": "10.1158/1535-7163.MCT-22-0655", "CorpusId": 253266395, + "PubMed": "36325690"}, "corpusId": 253266395, "publicationVenue": {"id": "05590b5e-de5a-404d-bec3-bfe1e9d96382", + "name": "Molecular Cancer Therapeutics", "type": "journal", "alternate_names": + ["Mol Cancer Ther"], "issn": "1535-7163", "url": "https://mct.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/a878a8e06a3770e4c23a9304e5daa6150bb9fd91", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Molecular Cancer Therapeutics", "year": + 2022, "referenceCount": 1, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Education", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-11-03", "journal": {"volume": "21 11", "pages": "\n 1625-1631\n ", + "name": "Molecular cancer therapeutics"}, "authors": [{"authorId": "2178880764", + "name": "Kenneth C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2149691856", "name": "Riccardo Dalla-Favera"}, {"authorId": + "2059177512", "name": "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis + A Diaz"}, {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": "145213930", + "name": "K. Flaherty"}, {"authorId": "2069169888", "name": "Philip D. Greenberg"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "3286001", "name": + "E. Mardis"}, {"authorId": "4008854", "name": "E. Platz"}, {"authorId": "2059212154", + "name": "M. N. Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, + {"authorId": "2469902", "name": "L. Siu"}, {"authorId": "5866492", "name": + "B. Teicher"}]}, {"paperId": "aee4ba305609bb8995909db6e6bec4c81fdf1048", "externalIds": + {"DOI": "10.1158/1538-7445.am2022-162", "CorpusId": 249726980}, "corpusId": + 249726980, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/aee4ba305609bb8995909db6e6bec4c81fdf1048", + "title": "Abstract 162: Identification of novel targets of Serine/arginine-rich + protein-specific kinase 2", "abstract": "\n Altered metabolism is one of the + hallmarks of cancer cells, supporting aberrant proliferation and survival + in nutrient scarce and stressful environments. The reprogrammed metabolism + supports the acquisition of malignant traits, increasing cellular fitness + and providing a selective advantage in tumorigenesis. Multiple signaling cascades + converge to regulate cancer cell metabolism to maintain a delicate balance + between anabolic and catabolic processes, with the overall goal to fuel ATP + production, biosynthesis of macromolecules and maintaining redox balance. + Specifically, 70% of human cancers have hyperactivated mechanistic target + of rapamycin (mTOR) signaling, the master regulator of cellular metabolism. + As an important signaling node, mTOR complex 1(mTORC1) integrates upstream + stimuli such as growth factors, amino acids and oxygen levels to regulate + a myriad of anabolic processes including protein and nucleotide synthesis, + RNA biogenesis and lipid metabolism, thereby promoting cell growth. The highly + proliferative state of cancer cells, coupled with a change in energy demands, + forces these cells to rewire their cellular metabolism to increase production + of cellular building blocks like proteins, lipids and nucleotides. De novo + lipogenesis provides lipids which act as an integral component of the plasma + membrane as well as functioning as signaling molecules. In addition to promoting + various anabolic processes, our lab has demonstrated that mTORC1-activated + serine/arginine-rich protein-specific kinase 2 (SRPK2) phosphorylates splicing + factors that stabilize lipogenic transcripts, protecting them from nonsense-mediated + decay and thereby increasing de novo lipogenesis. This is in contrast to another + serine/arginine-rich protein-specific kinase 1 (SRPK1), which is not regulated + by mTORC1. Inhibition of the mTORC1-SRPK2 signaling axis blunts de novo lipogenesis + and impedes tumor growth in several tumor xenograft models. SRPK2 overexpression + is also observed in lung and colon cancers, suggesting SRPK2 may promote the + growth of some human tumors. Despite the emerging role for SRPK2 in tumor + growth, very few substrates of this kinase are known. We conducted a phospho-proteomics + screen to identify novel substrates of SRPK1 and SRPK2. While some of the + targets we identified are regulated in an mTORC1-dependent manner, many appear + to be regulated independent of mTORC1, such as PTP1B, EGLN1 and EI24. We hypothesize + that these mTORC1-independent targets could be SRPK1-dependent revealing potential + distinct branches of SRPK signaling. Future studies will focus on not only + validating a subset of these novel targets and their role in tumor growth, + but also on exploring mTORC1-dependent and independent SRPK signaling.\n Citation + Format: Kripa Shobana Ganesh, Bethany Schaffer, Gina Lee, Jared Johnson, Tomer + M. Yaron, Noah Dephoure, Lewis C. Cantley, John Blenis. Identification of + novel targets of Serine/arginine-rich protein-specific kinase 2 [abstract]. + In: Proceedings of the American Association for Cancer Research Annual Meeting + 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract + nr 162.", "venue": "Cancer Research", "year": 2022, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2022-06-15", + "journal": {"name": "Cancer Research"}, "authors": [{"authorId": "144066592", + "name": "Kripa Ganesh"}, {"authorId": "31358846", "name": "B. Schaffer"}, + {"authorId": "2157397749", "name": "G. Lee"}, {"authorId": "145916288", "name": + "Jared L. Johnson"}, {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": + "4622316", "name": "Noah Dephoure"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4037343", "name": "J. Blenis"}]}, {"paperId": "afbfc30d640d578663e0b6ba55294d0862dca11a", + "externalIds": {"DOI": "10.1158/1538-7445.am2022-981", "CorpusId": 249721835}, + "corpusId": 249721835, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/afbfc30d640d578663e0b6ba55294d0862dca11a", + "title": "Abstract 981: A genetic-metabolic axis of metastatic liver organotropism", + "abstract": "\n Genomic and adaptive determinants of organ-specific metastasis + are poorly understood. A model of sequential acquisition of divergent somatic + mutations is insufficient to explain metastasis. Liver metastasis (LM) occurs + frequently and is associated with a poor prognosis and reduced therapy response + in several cancers, including in patients with melanoma and lung cancer. To + identify drivers of metastatic niches, we used a syngeneic mouse melanoma + model which recapitulates genomic, metastatic and therapy response patterns + seen in patients. We performed a large-scale in vivo CRISPR-Cas9 knockout + screen and identified perturbations that promote LM, but not primary tumor + growth or metastasis to other organs (e.g. lung). The \u201ctop hit\u201d + in this screen associated with LM was loss Pip4k2c. We generated Pip4k2cKO + cells and show that in otherwise isogenic melanoma cell lines, loss of Pip4k2c + led to increased baseline and insulin-induced activation of the PI3K/AKT pathway, + and increased invasive capacity. Rescuing Pip4k2cKO with full-length (Pip4k2cRec) + or allosteric domain deficient (Pip4k2cAD) Pip4k2c ORFs, we show that hyperactivation + of the PI3K/AKT pathway in is mediated by loss of the allosteric domain function, + and not loss of the kinase domain of Pip4k2c. Treatment with different PI3K + inhibitors effectively abrogated the pathway, but was partly bypassed in the + presence of insulin in Pip4k2cKO and Pip4k2cAD, but not parental or Pip4k2cRec + cells. Upon tail vein injection, Pip4k2cKO cells produced a significantly + increased LM burden compared to parental cells, and this effect was rescued + in Pip4k2cRec but not Pip4k2cAD, further affirming that loss of allosteric + domain was required for this phenotype. We reasoned that Pip4k2cKO cells preferentially + colonized the liver by co-opting the insulin-rich milieu in this organ. To + test this, we used shRNA targeted against the insulin receptor (Insr) generated + Pip4k2cKO/InsrshIR and showed that Insr was required but not sufficient to + enhance LM burden. Given the promising in vitro activity of PI3K inhibitors, + we next tested whether these could abrogate LM in vivo. Surprisingly, we found + a substantial increase in LM burden in mice with Pip4k2cKO-bearing LM treated + with PI3K inhibition compared to vehicle treated animals. We show that this + paradoxical observation was due to host-mediated increased in glucose and + insulin in response to PI3K inhibitor, which promoted a forward loop of increased + liver metastasis. Breaking this loop with either ketogenic diet or treatment + with a SGLT2 inhibitor in turn rescued increased these host responses and + resulted in reduced LM burden in combination with PI3K inhibition. In summary, + we identify a novel mechanism of metastatic liver organotropism and pharmacological + and dietary combinations to reduced liver metastatic burden. Given the expanding + use of PI3K inhibitors, our findings may have important clinical implications.\n + Citation Format: Meri Rogava, Johannes C. Melms, Stephanie Davis, Clemens + Hug, Bryan Ngo, Michael J. Lee, Patricia Ho, Amit Dipak Amin, Yiping Wang, + Sean Chen, William Ge, David Liu, Thomas T\u00fcting, Martin R\u00f6cken, + Thomas K. Eigentler, Samuel F. Bakhoum, Andrei Molotkov, Akiva Mintz, Lewis + C. Cantley, Peter K. Sorger, Benjamin Izar. A genetic-metabolic axis of metastatic + liver organotropism [abstract]. In: Proceedings of the American Association + for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): + AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 981.", "venue": "Cancer Research", + "year": 2022, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2022-06-15", "journal": {"name": "Cancer Research"}, "authors": + [{"authorId": "5255438", "name": "Meri Rogava"}, {"authorId": "51047419", + "name": "Johannes C. Melms"}, {"authorId": "145134818", "name": "Stephanie + H. Davis"}, {"authorId": "8667141", "name": "C. Hug"}, {"authorId": "5891999", + "name": "B. Ngo"}, {"authorId": "2115303865", "name": "Michael J. Lee"}, {"authorId": + "122989121", "name": "P. Ho"}, {"authorId": "35444784", "name": "A. Amin"}, + {"authorId": "2130357530", "name": "Yiping Wang"}, {"authorId": "2133441787", + "name": "Sean W Chen"}, {"authorId": "2170569496", "name": "William Ge"}, + {"authorId": "2145010756", "name": "David Liu"}, {"authorId": "4693025", "name": + "T. T\u00fcting"}, {"authorId": "49365056", "name": "M. R\u00f6cken"}, {"authorId": + "3513959", "name": "T. Eigentler"}, {"authorId": "3543494", "name": "S. Bakhoum"}, + {"authorId": "2071317850", "name": "A. Molotkov"}, {"authorId": "3572270", + "name": "A. Mintz"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2066157320", "name": "P. Sorger"}, {"authorId": "6923907", "name": "B. Izar"}]}, + {"paperId": "b1e64c48c765a33732688665333c7c6df7082546", "externalIds": {"PubMedCentral": + "9584945", "DOI": "10.1038/s41467-022-33862-0", "CorpusId": 253041901, "PubMed": + "36266345"}, "corpusId": 253041901, "publicationVenue": {"id": "43b3f0f9-489a-4566-8164-02fafde3cd98", + "name": "Nature Communications", "type": "journal", "alternate_names": ["Nat + Commun"], "issn": "2041-1723", "url": "https://www.nature.com/ncomms/", "alternate_urls": + ["http://www.nature.com/ncomms/about/index.html", "http://www.nature.com/ncomms/index.html"]}, + "url": "https://www.semanticscholar.org/paper/b1e64c48c765a33732688665333c7c6df7082546", + "title": "Tumor-produced and aging-associated oncometabolite methylmalonic + acid promotes cancer-associated fibroblast activation to drive metastatic + progression", "abstract": null, "venue": "Nature Communications", "year": + 2022, "referenceCount": 56, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/s41467-022-33862-0.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-10-20", "journal": {"volume": "13", "name": "Nature + Communications"}, "authors": [{"authorId": "13676191", "name": "Zhongchi Li"}, + {"authorId": "121128193", "name": "V. Low"}, {"authorId": "6052155", "name": + "V. Luga"}, {"authorId": "2110677133", "name": "Janet Y. Sun"}, {"authorId": + "2126900564", "name": "Ethan M Earlie"}, {"authorId": "6375303", "name": "Bobak + Parang"}, {"authorId": "2188427564", "name": "Kripa Shobana Ganesh"}, {"authorId": + "4051887", "name": "Sungyun Cho"}, {"authorId": "83689245", "name": "J. Endress"}, + {"authorId": "50356549", "name": "Tanya Schild"}, {"authorId": "47603369", + "name": "Mengying Hu"}, {"authorId": "49293831", "name": "D. Lyden"}, {"authorId": + "2188393051", "name": "Wenbing Jin"}, {"authorId": "2170974216", "name": "Chunjun + Guo"}, {"authorId": "4622316", "name": "Noah Dephoure"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "3009053", "name": "Ashley M. Laughney"}, + {"authorId": "4037343", "name": "J. Blenis"}]}, {"paperId": "b99f18c6c7336aa896d2766c4a2e46b39b0c6e4f", + "externalIds": {"PubMedCentral": "9011027", "DOI": "10.1016/j.gore.2022.100974", + "CorpusId": 247882578, "PubMed": "35434236"}, "corpusId": 247882578, "publicationVenue": + {"id": "753bdea8-6488-43c7-89cf-6a9f5897123c", "name": "Gynecologic Oncology + Reports", "type": "journal", "alternate_names": ["Gynecologic oncology reports", + "Gynecol oncol rep", "Gynecol Oncol Rep"], "issn": "2352-5789", "url": "https://www.journals.elsevier.com/gynecologic-oncology-reports/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/23525789"]}, + "url": "https://www.semanticscholar.org/paper/b99f18c6c7336aa896d2766c4a2e46b39b0c6e4f", + "title": "A phase II study of MK-2206, an AKT inhibitor, in uterine serous + carcinoma", "abstract": null, "venue": "Gynecologic Oncology Reports", "year": + 2022, "referenceCount": 15, "citationCount": 5, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["CaseReport"], "publicationDate": "2022-03-01", "journal": + {"volume": "40", "name": "Gynecologic Oncology Reports"}, "authors": [{"authorId": + "40406162", "name": "E. Stover"}, {"authorId": "1867565334", "name": "N. Xiong"}, + {"authorId": "6324437", "name": "A. Myers"}, {"authorId": "4518265", "name": + "N. Tayob"}, {"authorId": "2161108934", "name": "Victoria Engvold"}, {"authorId": + "51160410", "name": "Madeline Polak"}, {"authorId": "6416382", "name": "R. + Broaddus"}, {"authorId": "3553012", "name": "V. Makker"}, {"authorId": "5340828", + "name": "R. Drapkin"}, {"authorId": "2108419806", "name": "Joyce F. Liu"}, + {"authorId": "8523393", "name": "N. Horowitz"}, {"authorId": "1397965147", + "name": "F. Meric-Bernstam"}, {"authorId": "6128162", "name": "C. Aghajanian"}, + {"authorId": "3124983", "name": "R. Coleman"}, {"authorId": "2084778769", + "name": "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "6927295", "name": "U. Matulonis"}, {"authorId": "2974900", "name": "S. Westin"}, + {"authorId": "49610180", "name": "P. Konstantinopoulos"}]}, {"paperId": "ba279253ef001c2ba482811998fd701f81ec6463", + "externalIds": {"PubMedCentral": "9216717", "DOI": "10.1101/2022.06.16.496428", + "CorpusId": 249854522, "PubMed": "35734085"}, "corpusId": 249854522, "publicationVenue": + {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": "bioRxiv", "type": + "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/ba279253ef001c2ba482811998fd701f81ec6463", + "title": "Evolution of host protease interactions among SARS-CoV-2 variants + of concern and related coronaviruses", "abstract": "Previously, we showed + that coagulation factors directly cleave SARS-CoV-2 spike and promote viral + entry (Kastenhuber et al., 2022). Here, we show that substitutions in the + S1/S2 cleavage site observed in SARS-CoV-2 variants of concern (VOCs) exhibit + divergent interactions with host proteases, including factor Xa and furin. + Nafamostat remains effective to block coagulation factor-mediated cleavage + of variant spike sequences. Furthermore, host protease usage has likely been + a selection pressure throughout coronavirus evolution, and we observe convergence + of distantly related coronaviruses to attain common host protease interactions, + including coagulation factors. Interpretation of genomic surveillance of emerging + SARS-CoV-2 variants and future zoonotic spillover is supported by functional + characterization of recurrent emerging features.", "venue": "bioRxiv", "year": + 2022, "referenceCount": 69, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2022-06-16", + "journal": {"name": "bioRxiv"}, "authors": [{"authorId": "4306515", "name": + "Edward R. Kastenhuber"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, + {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": "2042047500", + "name": "Marisa N Mercadante"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "bc99b74ec0dfa86f06cd4d74b88bc9fd5e30d493", "externalIds": {"DOI": + "10.1158/2326-6066.CIR-22-0782", "CorpusId": 253258361, "PubMed": "36321298"}, + "corpusId": 253258361, "publicationVenue": {"id": "65d10e90-2076-49fd-b6f4-070cf4edad5b", + "name": "Cancer immunology research", "type": "journal", "alternate_names": + ["Cancer immunol res"], "issn": "2326-6066", "url": "https://cancerimmunolres.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/bc99b74ec0dfa86f06cd4d74b88bc9fd5e30d493", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Cancer immunology research", "year": + 2022, "referenceCount": 1, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Education", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-11-02", "journal": {"volume": "10 11", "pages": "\n 1282-1288\n ", + "name": "Cancer immunology research"}, "authors": [{"authorId": "2178880764", + "name": "Kenneth C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1396265158", "name": "R. Dalla-Favera"}, {"authorId": "2059177512", + "name": "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis A Diaz"}, + {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": "145213930", "name": + "K. Flaherty"}, {"authorId": "2069169888", "name": "Philip D. Greenberg"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "3286001", "name": + "E. Mardis"}, {"authorId": "4008854", "name": "E. Platz"}, {"authorId": "2059212154", + "name": "M. N. Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, + {"authorId": "2469902", "name": "L. Siu"}, {"authorId": "5866492", "name": + "B. Teicher"}]}, {"paperId": "be8a3bca32a5d86b9c556d6ab7dd6f330e13fb17", "externalIds": + {"PubMedCentral": "9352307", "DOI": "10.1021/acs.biochem.2c00123", "CorpusId": + 250453623, "PubMed": "35819845"}, "corpusId": 250453623, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/be8a3bca32a5d86b9c556d6ab7dd6f330e13fb17", + "title": "Discovery and Characterization of a Novel Allosteric Small-Molecule + Inhibitor of NADP+-Dependent Malic Enzyme 1", "abstract": "NADP+-dependent + malic enzyme 1 (ME1) decarboxylates malate to form pyruvate and NADPH in the + cytoplasm, where it mediates diverse biological functions related to the generation + of lipids and other cellular building blocks. As such, ME1 has been implicated + in the progression of cancers and has received attention as a promising drug + target. Here we report the identification of a novel small-molecule inhibitor + of ME1, designated AS1134900. AS1134900 is highly selective for ME1 compared + with ME2 and uncompetitively inhibits ME1 activity in the presence of its + substrates NADP+ and malate. In addition, X-ray crystal structure analysis + of the enzyme\u2013inhibitor complex revealed that AS1134900 binds outside + the ME1 active site in a novel allosteric site. Structural comparison of the + ME1 quaternary complex with AS1134900, NADPH, and Mn2+, alongside known crystal + structures of malic enzymes, indicated the determined crystal ME1\u2013inhibitor + complex is in the open form conformation. These results provide insights and + a starting point for further discovery of drugs that inhibit ME1 activity + in cancer cells.", "venue": "Biochemistry", "year": 2022, "referenceCount": + 16, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-07-12", "journal": {"volume": "61", "pages": "1548 + - 1553", "name": "Biochemistry"}, "authors": [{"authorId": "46875269", "name": + "Tomohiro Yoshida"}, {"authorId": "1517006580", "name": "Tetsuhiro Kawabe"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4901222", "name": + "C. Lyssiotis"}]}, {"paperId": "c544cb4ed7f8964954833e3931db9365ba39577d", + "externalIds": {"DOI": "10.1101/2022.07.29.502090", "CorpusId": 251323122}, + "corpusId": 251323122, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/c544cb4ed7f8964954833e3931db9365ba39577d", + "title": "Obesity promotes breast epithelium DNA damage in BRCA mutation carriers", + "abstract": "Obesity is an established risk factor for breast cancer among + women in the general population after menopause. Whether elevated bodyweight + is a risk factor for women with a germline mutation in BRCA1 or BRCA2 is less + clear due to inconsistent findings from epidemiological studies and lack of + mechanistic studies in this population. Here, we show that DNA damage in normal + breast epithelium of BRCA mutation carriers is positively correlated with + body mass index and with biomarkers of metabolic dysfunction. Additionally, + RNA-sequencing reveals significant obesity-associated alterations to the breast + adipose microenvironment of BRCA mutation carriers, including activation of + estrogen biosynthesis, which impacts neighboring breast epithelial cells. + We found that blockade of estrogen biosynthesis or estrogen receptor activity + decreases DNA damage, whereas treatment with leptin or insulin increases DNA + damage in BRCA heterozygous epithelial cells. Furthermore, we show that increased + adiposity is associated with mammary gland DNA damage and increased penetrance + of mammary tumors in Brca1+/- mice. Overall, our results provide mechanistic + evidence in support of a link between bodyweight and breast cancer development + in BRCA mutation carriers and suggests that maintaining a healthy bodyweight + or pharmacologically targeting estrogen or metabolic dysfunction may reduce + the risk of breast cancer in this population. One Sentence Summary Elevated + bodyweight is positively associated with DNA damage in breast epithelium of + BRCA mutation carriers", "venue": "bioRxiv", "year": 2022, "referenceCount": + 123, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.biorxiv.org/content/biorxiv/early/2022/08/02/2022.07.29.502090.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2022-08-02", "journal": {"name": "bioRxiv"}, "authors": + [{"authorId": "38811957", "name": "Priya Bhardwaj"}, {"authorId": "4018492", + "name": "N. Iyengar"}, {"authorId": "34651211", "name": "Heba Zahid"}, {"authorId": + "1961806917", "name": "Katharine M. Carter"}, {"authorId": "1884946007", "name": + "Dong Jun Byun"}, {"authorId": "8860004", "name": "Man-Ho Choi"}, {"authorId": + "2149098057", "name": "Qi Sun"}, {"authorId": "13774442", "name": "O. Savenkov"}, + {"authorId": "2180407428", "name": "Charalambia Louka"}, {"authorId": "2116905534", + "name": "Catherine Liu"}, {"authorId": "2126991989", "name": "Phoebe Piloco"}, + {"authorId": "2180408384", "name": "Monica Acosta"}, {"authorId": "9753461", + "name": "R. Bareja"}, {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": + "3813868", "name": "M. Foronda"}, {"authorId": "3918769", "name": "L. Dow"}, + {"authorId": "80751685", "name": "Sofya Oshchepkova"}, {"authorId": "4227896", + "name": "D. Giri"}, {"authorId": "78091495", "name": "M. Pollak"}, {"authorId": + "2109614954", "name": "X. Zhou"}, {"authorId": "48821307", "name": "B. Hopkins"}, + {"authorId": "3009053", "name": "Ashley M. Laughney"}, {"authorId": "4396333", + "name": "M. Frey"}, {"authorId": "6288829", "name": "L. Ellenson"}, {"authorId": + "144607636", "name": "M. Morrow"}, {"authorId": "4963563", "name": "J. Spector"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2246730", "name": + "K. Brown"}]}, {"paperId": "c920f5a95411852de842ce3dcdfc6e2b612f467b", "externalIds": + {"DOI": "10.1101/2022.05.22.492882", "CorpusId": 249047830}, "corpusId": 249047830, + "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": + "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/c920f5a95411852de842ce3dcdfc6e2b612f467b", + "title": "A global atlas of substrate specificities for the human serine/threonine + kinome", "abstract": "Protein phosphorylation is one of the most widespread + post-translational modifications in biology. With the advent of mass spectrometry-based + phosphoproteomics, more than 200,000 sites of serine and threonine phosphorylation + have been reported, of which several thousand have been associated with human + diseases and biological processes. For the vast majority of phosphorylation + events, it is not yet known which of the more than 300 protein Ser/Thr kinases + encoded in the human genome is responsible. Here, we utilize synthetic peptide + libraries to profile the substrate sequence specificity of nearly every functional + human Ser/Thr kinase. Viewed in its entirety, the substrate specificity of + the kinome was substantially more diverse than expected and was driven extensively + by negative selectivity. Our kinome-wide dataset was used to computationally + annotate and identify the most likely protein kinases for every reported phosphorylation + site in the human Ser/Thr phosphoproteome. For the small minority of phosphosites + where the protein kinases involved have been previously identified, our predictions + were in excellent agreement. When this approach was applied to examine the + signaling response of tissues and cell lines to hormones, growth factors, + targeted inhibitors, and environmental or genetic perturbations, it revealed + unexpected insights into pathway complexity and compensation. Overall, these + studies reveal the full extent of substrate specificity of the human Ser/Thr + kinome, illuminate cellular signaling responses, and provide a rich resource + to link unannotated phosphorylation events to biological pathways.", "venue": + "bioRxiv", "year": 2022, "referenceCount": 31, "citationCount": 7, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.biorxiv.org/content/biorxiv/early/2022/05/23/2022.05.22.492882.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2022-05-23", "journal": {"name": "bioRxiv"}, "authors": + [{"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": "5247030", + "name": "Tomer M. Yaron"}, {"authorId": "2137359212", "name": "Emily M. Huntsman"}, + {"authorId": "14658204", "name": "A. Kerelsky"}, {"authorId": "2144577350", + "name": "J. Song"}, {"authorId": "2166242001", "name": "Amit Regev"}, {"authorId": + "144181325", "name": "Ting-Yu Lin"}, {"authorId": "51910553", "name": "Katarina + M Liberatore"}, {"authorId": "2152463969", "name": "Daniel M. Cizin"}, {"authorId": + "2055611292", "name": "B. M. Cohen"}, {"authorId": "35123724", "name": "N. + Vasan"}, {"authorId": "50032234", "name": "Yilun Ma"}, {"authorId": "49181291", + "name": "Konstantin Krismer"}, {"authorId": "2124145062", "name": "Jaylissa + Torres Robles"}, {"authorId": "49094504", "name": "B. van de Kooij"}, {"authorId": + "1601471755", "name": "Anne van Vlimmeren"}, {"authorId": "1447106051", "name": + "Nicole Andr\u00e9e-Busch"}, {"authorId": "88029761", "name": "N. K\u00e4ufer"}, + {"authorId": "6547314", "name": "M. Dorovkov"}, {"authorId": "4097704", "name": + "A. Ryazanov"}, {"authorId": "49710109", "name": "Y. Takagi"}, {"authorId": + "4306515", "name": "Edward R. Kastenhuber"}, {"authorId": "145524334", "name": + "M. Goncalves"}, {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": + "34762957", "name": "D. Taatjes"}, {"authorId": "4165148", "name": "A. Maucuer"}, + {"authorId": "144561115", "name": "A. Yamashita"}, {"authorId": "145919811", + "name": "A. Degterev"}, {"authorId": "1892258", "name": "R. Linding"}, {"authorId": + "4037343", "name": "J. Blenis"}, {"authorId": "46627576", "name": "P. Hornbeck"}, + {"authorId": "25581223", "name": "B. Turk"}, {"authorId": "88402408", "name": + "M. Yaffe"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "dee8b56119d506d203ff44191db06dfe36380e91", "externalIds": {"DOI": "10.1158/1538-7445.am2022-794", + "CorpusId": 249729792}, "corpusId": 249729792, "publicationVenue": {"id": + "b0bd78b2-6591-460e-af71-196409b62e2c", "name": "Cancer Research", "type": + "journal", "alternate_names": ["Cancer Res"], "issn": "0008-5472", "url": + "https://cancerres.aacrjournals.org/", "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/dee8b56119d506d203ff44191db06dfe36380e91", + "title": "Abstract 794: Pan-cancer proteogenomic analysis reveals functional + mechanisms underlying DNA repair deficiencies", "abstract": "\n Emerging classifiers + that leverage recent advances in the characterization of mutational signatures + have identified a broader range of cancer patients with DNA repair deficiencies, + many of whom do not harbor mutations or epigenetic silencing of canonical + DNA repair genes. Investigating the various mechanisms underlying dysfunctional + DNA damage response (DDR) and heterogeneity across patients will be crucial + to understand disparate responses to therapy, including to PARP1 inhibitors + and to immunotherapy. In this study, we integrate genomic, transcriptomic, + proteomic, and post-translational modification (PTM) data across 11 cancer + types to elucidate the diverse functional mechanisms of DNA repair deficiencies + and their therapeutic implications through an in-depth proteogenomic analysis. + We first characterized the landscape of mutational signatures in 1110 patients + by applying SignatureAnalyzer, a tool that uses a Bayesian non-negative matrix + factorization method to discover patterns of somatic mutations. Our analysis + identified 144 homologous recombination-deficient (HRD) and 60 mismatch repair-deficient + (MMRD) patients. Multi-omic (mRNA, protein, PTMs) signature based hierarchical + clustering revealed two distinct clusters of HRD patients defined by either + (i) acute or (ii) chronic hypoxic states. The acute hypoxia cluster exhibited + typical HRD phenotypes, including a preference for non-homologous end joining + (NHEJ) and enrichment in PARP1 activity, as well as phosphorylation patterns + driven by DNA-PKcs, ATM, and ATR. In contrast, tumors under chronic hypoxia + exhibited a halting of replication and silencing of DDR, suggesting that patients + with these tumors may respond poorly to common HRD treatments that exploit + alternative error-prone repair and PARP1 activation. Notably, these tumors + were enriched in signatures representative of highly active kinases involved + in cellular stress responses, potentially providing additional avenues for + therapy. Additional analysis of both HRD and MMRD tumors revealed groups of + highly immunogenic DNA repair-deficient tumors that may respond well to some + types of immunotherapy given their increased mutagenesis. Moreover, differences + in inflammation-related kinase activities offer further insight into the interaction + between faulty DDR and the innate immune response (e.g., alterations in the + cGAS-STING DNA sensing pathway). Overall, our multi-omic signature analysis + provides insights into the mechanisms underlying DDR and its crosstalk with + other cancer-related pathways that remain unexplained by evaluating genomic + and transcriptomic data alone. Our characterization of the heterogeneity within + the population of patients with DNA repair deficiency shows promise for improved + prediction of treatment response, as well as identifying additional potential + therapeutic targets.\n Citation Format: Yo Akiyama, Yifat Geffen, Shankara + Anand, Tomer Yaron, Jared L. Johnson, Emily Huntsman, David Heiman, Chet Birger, + Karl Clauser, \u00d6zg\u00fcn Babur, Mendy Miller, Karsten Krug, D R Mani, + Lewis C. Cantley, Steven A. Carr, PanCancer Oncogenic Drivers and Pathways + Group, Clinical Proteomic Tumor Analysis Consortium (CPTAC), Francois Aguet, + Li Ding, Gad Getz. Pan-cancer proteogenomic analysis reveals functional mechanisms + underlying DNA repair deficiencies [abstract]. In: Proceedings of the American + Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia + (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 794.", "venue": "Cancer + Research", "year": 2022, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2022-06-15", "journal": {"name": "Cancer Research"}, "authors": + [{"authorId": "116703773", "name": "Yoshie Akiyama"}, {"authorId": "16307269", + "name": "Y. Geffen"}, {"authorId": "48361643", "name": "Shankara K. Anand"}, + {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": "145916288", + "name": "Jared L. Johnson"}, {"authorId": "2137359212", "name": "Emily M. + Huntsman"}, {"authorId": "37329835", "name": "David I. Heiman"}, {"authorId": + "69878839", "name": "Chet Birger"}, {"authorId": "2097664941", "name": "K. + Clauser"}, {"authorId": "8017947", "name": "\u00d6zg\u00fcn Babur"}, {"authorId": + "3004576", "name": "Mendy Miller"}, {"authorId": "40329575", "name": "K. Krug"}, + {"authorId": "2073717971", "name": "D. Mani"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2072711707", "name": "Steve Carr"}, {"authorId": + "48975912", "name": "F. Aguet"}, {"authorId": "49594724", "name": "L. Ding"}, + {"authorId": "2110594", "name": "G. Getz"}]}, {"paperId": "e29d68e46df33890982df05a67f3ad1231cfe6fe", + "externalIds": {"DOI": "10.1038/s41571-022-00633-1", "CorpusId": 248423779, + "PubMed": "35484287"}, "corpusId": 248423779, "publicationVenue": {"id": "e665d258-d079-4464-9b33-2291ffb17a14", + "name": "Nature Reviews Clinical Oncology", "type": "journal", "alternate_names": + ["Nat Rev Clin Oncol"], "issn": "1759-4774", "url": "http://www.nature.com/nrclinonc/", + "alternate_urls": ["http://www.nature.com/nrclinonc", "http://www.nature.com/nrclinonc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/e29d68e46df33890982df05a67f3ad1231cfe6fe", + "title": "At a crossroads: how to translate the roles of PI3K in oncogenic + and metabolic signalling into improvements in cancer therapy", "abstract": + null, "venue": "Nature Reviews Clinical Oncology", "year": 2022, "referenceCount": + 185, "citationCount": 10, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2022-04-28", "journal": {"volume": + "19", "pages": "471 - 485", "name": "Nature Reviews Clinical Oncology"}, "authors": + [{"authorId": "35123724", "name": "N. Vasan"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "ece822a63264bf7d46c6cef759b899324b76559d", "externalIds": + {"DOI": "10.1158/2643-3230.BCD-22-0165", "CorpusId": 253257644, "PubMed": + "36321294"}, "corpusId": 253257644, "publicationVenue": {"id": "6b2d326f-e39b-464b-8359-1ef475cd7495", + "name": "Blood Cancer Discovery", "type": "journal", "alternate_names": ["Blood + Cancer Discov"], "issn": "2643-3230", "url": "https://bloodcancerdiscov.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/ece822a63264bf7d46c6cef759b899324b76559d", + "title": "The AACR Journals: Advancing Progress Toward the AACR''s 115-Year + Mission.", "abstract": null, "venue": "Blood Cancer Discovery", "year": 2022, + "referenceCount": 1, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Education", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2022-11-02", "journal": {"volume": "3 6", "pages": "\n 469-475\n ", + "name": "Blood cancer discovery"}, "authors": [{"authorId": "2178880764", + "name": "Kenneth C. Anderson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1396265158", "name": "R. Dalla-Favera"}, {"authorId": "2059177512", + "name": "C. V. Dang"}, {"authorId": "2189433262", "name": "Luis A Diaz"}, + {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": "145213930", "name": + "K. Flaherty"}, {"authorId": "2069169888", "name": "Philip D. Greenberg"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "3286001", "name": + "E. Mardis"}, {"authorId": "4008854", "name": "E. Platz"}, {"authorId": "2059212154", + "name": "M. N. Pollak"}, {"authorId": "39884192", "name": "R. Schreiber"}, + {"authorId": "2469902", "name": "L. Siu"}, {"authorId": "5866492", "name": + "B. Teicher"}]}, {"paperId": "f729e5d864f78dea013afec3f59a96429d888034", "externalIds": + {"PubMedCentral": "9830954", "DOI": "10.1126/scisignal.abm0808", "CorpusId": + 253119647, "PubMed": "36282911"}, "corpusId": 253119647, "publicationVenue": + {"id": "c0efe552-8a0a-41a7-8ce2-340fb0dbfe6f", "name": "Science Signaling", + "type": "journal", "alternate_names": ["Sci Signal"], "issn": "1945-0877", + "url": "https://www.sciencemag.org/", "alternate_urls": ["https://stke.sciencemag.org/about/", + "https://stke.sciencemag.org/"]}, "url": "https://www.semanticscholar.org/paper/f729e5d864f78dea013afec3f59a96429d888034", + "title": "Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation + and viral replication", "abstract": "Multiple coronaviruses have emerged independently + in the past 20 years that cause lethal human diseases. Although vaccine development + targeting these viruses has been accelerated substantially, there remain patients + requiring treatment who cannot be vaccinated or who experience breakthrough + infections. Understanding the common host factors necessary for the life cycles + of coronaviruses may reveal conserved therapeutic targets. Here, we used the + known substrate specificities of mammalian protein kinases to deconvolute + the sequence of phosphorylation events mediated by three host protein kinase + families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster + of serine and threonine residues in the viral N protein, which is required + for viral replication. We also showed that loss or inhibition of SRPK1/2, + which we propose initiates the N protein phosphorylation cascade, compromised + the viral replication cycle. Because these phosphorylation sites are highly + conserved across coronaviruses, inhibitors of these protein kinases not only + may have therapeutic potential against COVID-19 but also may be broadly useful + against coronavirus-mediated diseases. Description Inhibiting host kinases + that phosphorylate the SARS-CoV-2 nucleocapsid protein blocks viral replication. + Targeting the host instead of the virus Although vaccines have been very effective + in responding to the COVID-19 pandemic caused by the virus SARS-CoV-2, there + is a continuing need to develop new therapeutics. Through phosphoproteomic + analysis of SARS-CoV-2\u2013infected cells, Yaron et al. identified multiple + phosphorylation sites in a conserved region of the viral nucleocapsid (N) + protein, which is critical for viral replication. Biochemical analyses identified + the host kinases that sequentially phosphorylated distinct motifs in the N + protein, and knockdown or inhibition of members of the priming kinase family + SPRK reduced N protein phosphorylation. An FDA-approved drug that can inhibit + kinases of the SRPK family reduced N protein phosphorylation and blocked viral + replication in vitro, suggesting that the approach of targeting host proteins + required by the virus might have therapeutic potential in the treatment of + coronavirus-mediated infections.", "venue": "Science Signaling", "year": 2022, + "referenceCount": 96, "citationCount": 3, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2022-10-25", "journal": {"volume": "15", "pages": "eabm0808 - eabm0808", + "name": "Science signaling"}, "authors": [{"authorId": "5247030", "name": + "Tomer M. Yaron"}, {"authorId": "38692984", "name": "B. Heaton"}, {"authorId": + "32603328", "name": "T. Levy"}, {"authorId": "145916288", "name": "Jared L. + Johnson"}, {"authorId": "145658521", "name": "Tristan X. Jordan"}, {"authorId": + "2055611292", "name": "B. M. Cohen"}, {"authorId": "14658204", "name": "A. + Kerelsky"}, {"authorId": "144181325", "name": "Ting-Yu Lin"}, {"authorId": + "51910553", "name": "Katarina M Liberatore"}, {"authorId": "1931600430", "name": + "Danielle K Bulaon"}, {"authorId": "30572053", "name": "S. V. Van Nest"}, + {"authorId": "13532971", "name": "Nikos Koundouros"}, {"authorId": "4306515", + "name": "Edward R. Kastenhuber"}, {"authorId": "2042047500", "name": "Marisa + N Mercadante"}, {"authorId": "2042286049", "name": "Kripa Shobana-Ganesh"}, + {"authorId": "2112463843", "name": "Long He"}, {"authorId": "46462360", "name": + "R. Schwartz"}, {"authorId": "47336157", "name": "Shuibing Chen"}, {"authorId": + "50028113", "name": "H. Weinstein"}, {"authorId": "150097652", "name": "O. + Elemento"}, {"authorId": "6016224", "name": "E. Piskounova"}, {"authorId": + "1422205499", "name": "Benjamin E. Nilsson-Payant"}, {"authorId": "2123198", + "name": "Gina Lee"}, {"authorId": "66419419", "name": "Joseph D. Trimarco"}, + {"authorId": "2042240908", "name": "Kaitlyn N Burke"}, {"authorId": "30094094", + "name": "Cait E. Hamele"}, {"authorId": "6181769", "name": "Ryan R. Chaparian"}, + {"authorId": "16048806", "name": "Alfred T. Harding"}, {"authorId": "47203895", + "name": "Aleksandra Tata"}, {"authorId": "8361947", "name": "Xinyu Zhu"}, + {"authorId": "38101990", "name": "P. Tata"}, {"authorId": "2110209555", "name": + "Clare M. Smith"}, {"authorId": "6536164", "name": "A. Possemato"}, {"authorId": + "2188844191", "name": "Sasha L Tkachev"}, {"authorId": "46627576", "name": + "P. Hornbeck"}, {"authorId": "4424720", "name": "S. Beausoleil"}, {"authorId": + "48361643", "name": "Shankara K. Anand"}, {"authorId": "48975912", "name": + "F. Aguet"}, {"authorId": "153395395", "name": "G. Getz"}, {"authorId": "35178796", + "name": "A. Davidson"}, {"authorId": "4107601", "name": "K. Heesom"}, {"authorId": + "2042810306", "name": "M. Kavanagh-Williamson"}, {"authorId": "2055674540", + "name": "D. Matthews"}, {"authorId": "5462120", "name": "B. tenOever"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4037343", "name": "J. Blenis"}, + {"authorId": "35057532", "name": "N. Heaton"}]}, {"paperId": "fbef25965511124276964eec90a8db33a29cb3ae", + "externalIds": {"DOI": "10.1016/j.ejmech.2022.115027", "CorpusId": 255117733, + "PubMed": "36584631"}, "corpusId": 255117733, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/fbef25965511124276964eec90a8db33a29cb3ae", + "title": "Development of potent and selective degraders of PI5P4K\u03b3.", + "abstract": null, "venue": "European journal of medicinal chemistry", "year": + 2022, "referenceCount": 36, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2022-12-01", "journal": {"volume": "247", "pages": "\n 115027\n ", + "name": "European journal of medicinal chemistry"}, "authors": [{"authorId": + "50119404", "name": "Wenzhi Ji"}, {"authorId": "144962538", "name": "Eric + S. Wang"}, {"authorId": "16018077", "name": "Theresa D. Manz"}, {"authorId": + "143916454", "name": "Jie Jiang"}, {"authorId": "10775141", "name": "K. Donovan"}, + {"authorId": "26575358", "name": "Xianmixinuer Abulaiti"}, {"authorId": "145053102", + "name": "E. Fischer"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2262535", "name": "Tinghu Zhang"}, {"authorId": "3977406", "name": "N. Gray"}]}, + {"paperId": "09187a09993357927084c39a4dddf9d0fa8c4bca", "externalIds": {"DOI": + "10.1158/2159-8290.CD-21-0082", "CorpusId": 232018498, "PubMed": "33619209"}, + "corpusId": 232018498, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/09187a09993357927084c39a4dddf9d0fa8c4bca", + "title": "A Decade of Cancer Discovery.", "abstract": "As Cancer Discovery + turns 10, we reflect on the journal''s success and look ahead to the future.", + "venue": "Cancer Discovery", "year": 2021, "referenceCount": 11, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://aacrjournals.org/cancerdiscovery/article-pdf/11/4/795/3099338/795.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["Editorial"], "publicationDate": "2021-02-22", "journal": + {"name": "Cancer discovery"}, "authors": [{"authorId": "1381145942", "name": + "L. Diaz"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "0c4716ad7841684510816323fa58220445cefcca", + "externalIds": {"PubMedCentral": "7992237", "DOI": "10.1093/noajnl/vdab024.074", + "CorpusId": 232479878}, "corpusId": 232479878, "publicationVenue": {"id": + "4390a6c7-bd1a-4ccc-b9e6-e988368f95cb", "name": "Neuro-Oncology Advances", + "type": "journal", "alternate_names": ["Neuro-oncology Adv"], "issn": "2632-2498"}, + "url": "https://www.semanticscholar.org/paper/0c4716ad7841684510816323fa58220445cefcca", + "title": "FSMP-10. CYSTEINE INDUCES CYTOTOXICITY IN GLIOBLASTOMA THROUGH MITOCHONDRIAL + HYDROGEN PEROXIDE PRODUCTION", "abstract": "Abstract Glioblastoma (GBM) is + a poorly treatable disease with high mortality. Tumor metabolism in GBM is + a critical mechanism responsible for growth because of upregulation of glucose, + amino acid, and fatty acid utilization. However, little is known about the + specific metabolic alterations in GBM that are targetable with FDA-approved + compounds. To investigate metabolic signatures unique to GBM, we interrogated + the TCGA and a cancer metabolite database for alterations in glucose and amino + acid signatures in GBM relative to other human cancers and relative to low-grade + glioma. From these analyses, we found that GBM exhibits the highest levels + of cysteine and methionine pathway gene expression of 32 human cancers and + that GBM exhibits high levels of cysteine metabolites compared to low-grade + gliomas. To study the role of cysteine in GBM pathogenesis, we treated patient-derived + GBM cells with FDA-approved cyst(e)ine-promoting compounds in vitro, including + N-acetylcysteine (NAC) and the cephalosporin antibiotic, Ceftriaxone (CTX), + which induces cystine import through system Xc transporter upregulation. Cysteine-promoting + compounds, including NAC and CTX, inhibit growth of GBM cells, which is exacerbated + by glucose deprivation. This growth inhibition is associated with reduced + mitochondrial metabolism, manifest by reduction in ATP, NADPH/NADP+ ratio, + mitochondrial membrane potential, and oxygen consumption rate. Mechanistic + experiments revealed that cysteine compounds induce a rapid increase in the + rate of H2O2 production in isolated GBM mitochondria, an effect blocked by + the H2O2 scavenger, catalase. Such findings are consistent with reductive + stress, a ROS-producing process whereby excess mitochondrial reducing equivalents + prevent electron transfer to oxidized electron acceptors, inducing O2 reduction + to H2O2. We show that cysteine-promoting compounds reduce cell growth and + induce rapid mitochondrial toxicity in GBM, which may be due to reductive + stress. This pathway is targetable with FDA-approved cysteine-promoting compounds + and could synergize with glucose-lowering treatments, including the ketogenic + diet, for GBM.", "venue": "Neuro-Oncology Advances", "year": 2021, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://academic.oup.com/noa/article-pdf/3/Supplement_1/i18/36733834/vdab024.074.pdf", + "status": null}, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2021-03-01", + "journal": {"volume": "3", "pages": "i18 - i18", "name": "Neuro-oncology Advances"}, + "authors": [{"authorId": "3913142", "name": "E. Noch"}, {"authorId": "2065330100", + "name": "L. Palma"}, {"authorId": "1716222698", "name": "I. Yim"}, {"authorId": + "1454461390", "name": "Bhavneet Binder"}, {"authorId": "123664542", "name": + "E. Benedetti"}, {"authorId": "2067285", "name": "J. Krumsiek"}, {"authorId": + "150097652", "name": "O. Elemento"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "1098b27466f2336f0023f9cfcd4f106f63d6917f", "externalIds": {"MAG": + "3151637556", "DOI": "10.1038/S43018-021-00183-Y", "CorpusId": 233532015, + "PubMed": "34179825"}, "corpusId": 233532015, "publicationVenue": {"id": "f511c64e-b292-49b6-a819-65678fadeebb", + "name": "Nature Cancer", "type": "journal", "alternate_names": ["Nat Cancer"], + "issn": "2662-1347", "url": "https://www.nature.com/natcancer/"}, "url": "https://www.semanticscholar.org/paper/1098b27466f2336f0023f9cfcd4f106f63d6917f", + "title": "FATTY ACID SYNTHESIS IS REQUIRED FOR BREAST CANCER BRAIN METASTASIS.", + "abstract": null, "venue": "Nature Cancer", "year": 2021, "referenceCount": + 87, "citationCount": 61, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc8223728?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2021-04-01", "journal": {"volume": "2 4", "pages": "\n 414-428\n ", + "name": "Nature cancer"}, "authors": [{"authorId": "35545769", "name": "G. + Ferraro"}, {"authorId": "2157679423", "name": "A. Ali"}, {"authorId": "114311983", + "name": "Alba Luengo"}, {"authorId": "10029385", "name": "D. Kodack"}, {"authorId": + "2922270", "name": "A. Deik"}, {"authorId": "39862913", "name": "Keene L. + Abbott"}, {"authorId": "11045592", "name": "Divya Bezwada"}, {"authorId": + "29960670", "name": "L. Blanc"}, {"authorId": "4151707", "name": "Brendan + Prideaux"}, {"authorId": "2149169420", "name": "Xin Jin"}, {"authorId": "89996372", + "name": "Jessica M. Possada"}, {"authorId": "2144207912", "name": "Jiang Chen"}, + {"authorId": "2056653349", "name": "Christopher R Chin"}, {"authorId": "10042929", + "name": "Z. Amoozgar"}, {"authorId": "2067628106", "name": "Raphael Ferreira"}, + {"authorId": "19188310", "name": "Ivy X. Chen"}, {"authorId": "5110430", "name": + "K. Naxerova"}, {"authorId": "49689673", "name": "C. Ng"}, {"authorId": "115500939", + "name": "Anna M. Westermark"}, {"authorId": "40602288", "name": "M. Duquette"}, + {"authorId": "5239105", "name": "S. Roberge"}, {"authorId": "3734755", "name": + "N. Lindeman"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "145414907", "name": "J. Nielsen"}, {"authorId": "10127476", "name": "D. Housman"}, + {"authorId": "1678407", "name": "D. Duda"}, {"authorId": "6207661", "name": + "E. Brachtel"}, {"authorId": "2900051", "name": "T. Golub"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "34711277", "name": "Shawn M. Davidson"}, {"authorId": "3057625", + "name": "D. Fukumura"}, {"authorId": "3361348", "name": "V. Dartois"}, {"authorId": + "3633091", "name": "C. Clish"}, {"authorId": "32514332", "name": "R. Jain"}, + {"authorId": "3804233", "name": "M. V. Vander Heiden"}]}, {"paperId": "114f9ead1ca1165e2bd5a6254af4e39b23ceae89", + "externalIds": {"PubMedCentral": "9256808", "DOI": "10.1101/2021.05.09.443334", + "CorpusId": 234474789, "PubMed": "35584006"}, "corpusId": 234474789, "publicationVenue": + {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": "bioRxiv", "type": + "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/114f9ead1ca1165e2bd5a6254af4e39b23ceae89", + "title": "Pyruvate Kinase M1 Suppresses Development and Progression of Prostate + Adenocarcinoma", "abstract": "Most cancers, including prostate cancers, express + the M2 splice isoform of pyruvate kinase (Pkm2). This isoform can promote + anabolic metabolism to support cell proliferation; however, Pkm2 expression + is dispensable for many cancers in vivo. Pyruvate kinase M1 (Pkm1) isoform + expression is restricted to relatively few tissues and has been reported to + promote growth of select tumors, but the role of PKM1 in cancer has been less + studied. Pkm1 is expressed in normal prostate tissue; thus, to test how differential + pyruvate kinase isoform expression affects cancer initiation and progression + we generated mice harboring a conditional allele of Pkm1 and crossed this + allele, as well as a Pkm2 conditional allele, to a Pten loss-driven prostate + cancer model. We found that Pkm1 loss leads to Pkm2 expression and accelerates + prostate cancer, while deletion of Pkm2 leads to increased Pkm1 expression + and suppresses cancer. Consistent with these data, a small molecule pyruvate + kinase activator that mimics a PKM1-like state suppresses progression of established + prostate tumors. PKM2 expression is retained in most human prostate cancers, + arguing that pharmacological PKM2 activation may be beneficial for some prostate + cancer patients.", "venue": "bioRxiv", "year": 2021, "referenceCount": 67, + "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://dspace.mit.edu/bitstream/1721.1/147020/2/2403.pdf", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2021-05-10", "journal": {"volume": "82", "pages": "2403 + - 2416", "name": "Cancer Research"}, "authors": [{"authorId": "34711277", + "name": "Shawn M. Davidson"}, {"authorId": "2073832290", "name": "Julia Heyman"}, + {"authorId": "2066826610", "name": "James P O''Brien"}, {"authorId": "86899047", + "name": "Amy C. Liu"}, {"authorId": "49718538", "name": "D. R. Schmidt"}, + {"authorId": "5553029", "name": "W. J. Israelsen"}, {"authorId": "40576003", + "name": "T. Dayton"}, {"authorId": "40880369", "name": "Raghav Sehgal"}, {"authorId": + "40803408", "name": "R. Bronson"}, {"authorId": "5169232", "name": "Elizaveta + Freinkman"}, {"authorId": "10185930", "name": "H. Mak"}, {"authorId": "3870192", + "name": "S. Malstrom"}, {"authorId": "5679020", "name": "G. Bellinger"}, {"authorId": + "6988610", "name": "A. Carracedo"}, {"authorId": "4499580", "name": "P. Pandolfi"}, + {"authorId": "13782167", "name": "K. Courtney"}, {"authorId": "1788876", "name": + "J. Frangioni"}, {"authorId": "38884428", "name": "Abhishek Jha"}, {"authorId": + "5593407", "name": "R. DePinho"}, {"authorId": "40006904", "name": "J. Horner"}, + {"authorId": "2148769632", "name": "Craig J. Thomas"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "6213932", "name": "M. Loda"}, {"authorId": + "3804233", "name": "M. V. Vander Heiden"}]}, {"paperId": "144acb59f597d5db52f93f00bbb00922f545fc88", + "externalIds": {"DOI": "10.1038/s41571-021-00579-w", "CorpusId": 244492478, + "PubMed": "34819622"}, "corpusId": 244492478, "publicationVenue": {"id": "e665d258-d079-4464-9b33-2291ffb17a14", + "name": "Nature Reviews Clinical Oncology", "type": "journal", "alternate_names": + ["Nat Rev Clin Oncol"], "issn": "1759-4774", "url": "http://www.nature.com/nrclinonc/", + "alternate_urls": ["http://www.nature.com/nrclinonc", "http://www.nature.com/nrclinonc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/144acb59f597d5db52f93f00bbb00922f545fc88", + "title": "Radiotherapy as a tool to elicit clinically actionable signalling + pathways in cancer", "abstract": null, "venue": "Nature Reviews Clinical Oncology", + "year": 2021, "referenceCount": 404, "citationCount": 21, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "2021-11-24", + "journal": {"volume": "19", "pages": "114-131", "name": "Nature Reviews Clinical + Oncology"}, "authors": [{"authorId": "21711615", "name": "G. Petroni"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4204823", "name": "L. Santambrogio"}, + {"authorId": "145423973", "name": "S. Formenti"}, {"authorId": "3974364", + "name": "L. Galluzzi"}]}, {"paperId": "2db9debd53e753e13f5a11a2dde09035d7d460c6", + "externalIds": {"MAG": "3182483332", "DOI": "10.1158/1538-7445.AM2021-16", + "CorpusId": 237760821}, "corpusId": 237760821, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/2db9debd53e753e13f5a11a2dde09035d7d460c6", + "title": "Abstract 16: Patterns and regulation of post translational modifications + in cancer", "abstract": null, "venue": "Cancer Chemistry", "year": 2021, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}], "publicationTypes": null, "publicationDate": + "2021-07-01", "journal": {"name": "Cancer Chemistry"}, "authors": [{"authorId": + "16307269", "name": "Y. Geffen"}, {"authorId": "48361643", "name": "Shankara + K. Anand"}, {"authorId": "122529265", "name": "Yoshihisa Akiyama"}, {"authorId": + "2128934859", "name": "Tommer M. Yaron"}, {"authorId": "14658204", "name": + "A. Kerelsky"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "40329575", "name": "K. Krug"}, {"authorId": "37329835", "name": "David I. + Heiman"}, {"authorId": "34794500", "name": "S. Satpathy"}, {"authorId": "2097664941", + "name": "K. Clauser"}, {"authorId": "39595909", "name": "M. Gillette"}, {"authorId": + "2073717971", "name": "D. Mani"}, {"authorId": "69878839", "name": "Chet Birger"}, + {"authorId": "2072711707", "name": "Steve Carr"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "48975912", "name": "F. Aguet"}, {"authorId": + "2110594", "name": "G. Getz"}]}, {"paperId": "5ae2c149a0719a0d541f3061308aeb520f6fb696", + "externalIds": {"DOI": "10.1101/2021.08.20.457146", "CorpusId": 237271121}, + "corpusId": 237271121, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/5ae2c149a0719a0d541f3061308aeb520f6fb696", + "title": "SARS-CoV-2 hijacks p38\u03b2/MAPK11 to promote virus replication", + "abstract": "SARS-CoV-2, the causative agent of the COVID-19 pandemic, drastically + modifies infected cells in an effort to optimize virus replication. Included + is the activation of the host p38 mitogen-activated protein kinase (MAPK) + pathway, which plays a major role in inflammation and is a central driver + of COVID-19 clinical presentations. Inhibition of p38/MAPK activity in SARS-CoV-2-infected + cells reduces both cytokine production and viral replication. Here, we combined + genetic screening with quantitative phosphoproteomics to better understand + interactions between the p38/MAPK pathway and SARS-CoV-2. We found that several + components of the p38/MAPK pathway impacted SARS-CoV-2 replication and that + p38\u03b2 is a critical host factor for virus replication, and it prevents + activation of the type-I interferon pathway. Quantitative phosphoproteomics + uncovered several SARS-CoV-2 nucleocapsid phosphorylation sites near the N-terminus + that were sensitive to p38 inhibition. Similar to p38\u03b2 depletion, mutation + of these nucleocapsid residues was associated with reduced virus replication + and increased activation of type-I interferon signaling. Taken together, this + study reveals a unique proviral function for p38\u03b2 that is not shared + with p38\u03b1 and supports exploring p38\u03b2 inhibitor development as a + strategy towards developing a new class of COVID-19 therapies. Importance + SARS-CoV-2 is the causative agent of the COVID-19 pandemic that has claimed + millions of lives since its emergence in 2019. SARS-CoV-2 infection of human + cells requires the activity of several cellular pathways for successful replication. + One such pathway, the p38 mitogen-activated protein kinase (MAPK) pathway, + is required for virus replication and disease pathogenesis. Here, we applied + systems biology approaches to understand how MAPK pathways benefit SARS-CoV-2 + replication to inform the development of novel COVID-19 drug therapies.", + "venue": "bioRxiv", "year": 2021, "referenceCount": 65, "citationCount": 2, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.biorxiv.org/content/biorxiv/early/2022/09/14/2021.08.20.457146.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-08-20", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "21581175", "name": "Christina A. Higgins"}, + {"authorId": "1422205499", "name": "Benjamin E. Nilsson-Payant"}, {"authorId": + "2091925403", "name": "Andrew P. Kurland"}, {"authorId": "1820803613", "name": + "C. Ye"}, {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": + "145916288", "name": "Jared L. Johnson"}, {"authorId": "52034318", "name": + "Boris Bonaventure"}, {"authorId": "2124144278", "name": "Prithy Adhikary"}, + {"authorId": "1420415021", "name": "Ilona Golynker"}, {"authorId": "3579494", + "name": "M. Panis"}, {"authorId": "8777036", "name": "O. Danziger"}, {"authorId": + "39166273", "name": "Brad R. Rosenberg"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "1390112686", "name": "L. Mart\u00ednez-Sobrido"}, + {"authorId": "5462120", "name": "B. tenOever"}, {"authorId": "2185012922", + "name": "Jeffrey R. Johnson"}]}, {"paperId": "60e82aca861a616ba7a8e5d85edb14daca9197f6", + "externalIds": {"DOI": "10.1038/s41586-021-03827-2", "CorpusId": 237214802, + "PubMed": "34408323"}, "corpusId": 237214802, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/60e82aca861a616ba7a8e5d85edb14daca9197f6", + "title": "Dietary fructose improves intestinal cell survival and nutrient + absorption.", "abstract": null, "venue": "Nature", "year": 2021, "referenceCount": + 47, "citationCount": 55, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2021-08-18", "journal": + {"name": "Nature"}, "authors": [{"authorId": "2110994237", "name": "Samuel + R Taylor"}, {"authorId": "2058412873", "name": "Shakti Ramsamooj"}, {"authorId": + "46875693", "name": "R. Liang"}, {"authorId": "51042358", "name": "Alyna Katti"}, + {"authorId": "2123702437", "name": "Rita Pozovskiy"}, {"authorId": "35123724", + "name": "N. Vasan"}, {"authorId": "4151944", "name": "Seo-Kyoung Hwang"}, + {"authorId": "2046170895", "name": "Navid Nahiyaan"}, {"authorId": "4546655", + "name": "N. Francoeur"}, {"authorId": "4598930", "name": "Emma M Schatoff"}, + {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": "143609289", + "name": "Manish A. Shah"}, {"authorId": "3860528", "name": "A. Dannenberg"}, + {"authorId": "46517710", "name": "R. Sebra"}, {"authorId": "3918769", "name": + "L. Dow"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4097554", + "name": "K. Rhee"}, {"authorId": "145524334", "name": "M. Goncalves"}]}, {"paperId": + "62785cd4170382ba0da22cb4e4a7da687abf5d88", "externalIds": {"DOI": "10.1016/j.molcel.2021.06.029", + "CorpusId": 236000856, "PubMed": "34270944"}, "corpusId": 236000856, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/62785cd4170382ba0da22cb4e4a7da687abf5d88", + "title": "Editorial Note to: Glucose Addiction of TSC Null Cells Is Caused + by Failed mTORC1-Dependent Balancing of Metabolic Demand with Supply.", "abstract": + null, "venue": "Molecules and Cells", "year": 2021, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.cell.com/article/S1097276521005396/pdf", "status": null}, "fieldsOfStudy": + ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2021-07-15", "journal": + {"volume": "81 14", "pages": "\n 3031\n ", "name": "Molecular + cell"}, "authors": [{"authorId": "32210637", "name": "A. Y. Choo"}, {"authorId": + "46876889", "name": "Sang Gyun Kim"}, {"authorId": "3804233", "name": "M. + V. Vander Heiden"}, {"authorId": "48247811", "name": "S. J. Mahoney"}, {"authorId": + "46470616", "name": "H. Vu"}, {"authorId": "6168327", "name": "Sang-Oh Yoon"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4037343", "name": + "J. Blenis"}]}, {"paperId": "7bffa46e6a5270ccd086d48bb16202a5a66c8190", "externalIds": + {"DOI": "10.1101/2021.03.31.437960", "CorpusId": 233037086, "PubMed": "33821268"}, + "corpusId": 233037086, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/7bffa46e6a5270ccd086d48bb16202a5a66c8190", + "title": "Coagulation factors directly cleave SARS-CoV-2 spike and enhance + viral entry", "abstract": "Coagulopathy is recognized as a significant aspect + of morbidity in COVID-19 patients. The clotting cascade is propagated by a + series of proteases, including factor Xa and thrombin. Other host proteases, + including TMPRSS2, are recognized to be important for cleavage activation + of SARS-CoV-2 spike to promote viral entry. Using biochemical and cell-based + assays, we demonstrate that factor Xa and thrombin can also directly cleave + SARS-CoV-2 spike, enhancing viral entry. A drug-repurposing screen identified + a subset of protease inhibitors that promiscuously inhibited spike cleavage + by both transmembrane serine proteases as well as coagulation factors. The + mechanism of the protease inhibitors nafamostat and camostat extend beyond + inhibition of TMPRSS2 to coagulation-induced spike cleavage. Anticoagulation + is critical in the management of COVID-19, and early intervention could provide + collateral benefit by suppressing SARS-CoV-2 viral entry. We propose a model + of positive feedback whereby infection-induced hypercoagulation exacerbates + SARS-CoV-2 infectivity.", "venue": "bioRxiv", "year": 2021, "referenceCount": + 109, "citationCount": 21, "influentialCitationCount": 1, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-04-01", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "4306515", "name": "Edward R. Kastenhuber"}, + {"authorId": "31952434", "name": "Javier A. Jaimes"}, {"authorId": "145916288", + "name": "Jared L. Johnson"}, {"authorId": "2042047500", "name": "Marisa N + Mercadante"}, {"authorId": "3520712", "name": "F. Muecksch"}, {"authorId": + "1705035052", "name": "Y. Weisblum"}, {"authorId": "4785493", "name": "Y. + Bram"}, {"authorId": "46462360", "name": "R. Schwartz"}, {"authorId": "2779993", + "name": "G. Whittaker"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "7e8343ac14d336624675b4ee61a42e32a80c9512", "externalIds": {"MAG": + "3155082499", "DOI": "10.1158/1557-3265.RADSCI21-PO-051", "CorpusId": 234875594}, + "corpusId": 234875594, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7e8343ac14d336624675b4ee61a42e32a80c9512", + "title": "Abstract PO-051: Radiation therapy enhances the presentation of + phosphopeptides by MHC-I on cancer cells", "abstract": null, "venue": "", + "year": 2021, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}], "publicationTypes": + null, "publicationDate": "2021-04-15", "journal": {"volume": "", "name": ""}, + "authors": [{"authorId": "30572053", "name": "S. V. Van Nest"}, {"authorId": + "5247030", "name": "Tomer M. Yaron"}, {"authorId": "49124983", "name": "M. + Klatt"}, {"authorId": "4622316", "name": "Noah Dephoure"}, {"authorId": "2110594", + "name": "G. Getz"}, {"authorId": "4204823", "name": "L. Santambrogio"}, {"authorId": + "150097652", "name": "O. Elemento"}, {"authorId": "4864508", "name": "D. Scheinberg"}, + {"authorId": "46869413", "name": "S. Demaria"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "828310c09934c9a15b3cc88cab2de7a0363ca876", "externalIds": + {"PubMedCentral": "7992317", "DOI": "10.1093/noajnl/vdab024.029", "CorpusId": + 232480272}, "corpusId": 232480272, "publicationVenue": {"id": "4390a6c7-bd1a-4ccc-b9e6-e988368f95cb", + "name": "Neuro-Oncology Advances", "type": "journal", "alternate_names": ["Neuro-oncology + Adv"], "issn": "2632-2498"}, "url": "https://www.semanticscholar.org/paper/828310c09934c9a15b3cc88cab2de7a0363ca876", + "title": "DDRE-07. FATTY ACID SYNTHESIS IS REQUIRED FOR BREAST CANCER BRAIN + METASTASIS", "abstract": "Abstract Brain metastases are refractory to therapies + that otherwise control systemic disease in patients with human epidermal growth + factor receptor 2 (HER2+) breast cancer, and the unique brain microenvironment + contributes to this therapy resistance. Nutrient availability can vary across + tissues, therefore metabolic adaptations required for breast cancer growth + in the brain microenvironment may also introduce liabilities that can be exploited + for therapy. Here, we assessed how metabolism differs between breast tumors + growing in the brain versus extracranial sites and found that fatty acid synthesis + is elevated in breast tumors growing in the brain. We determine that this + phenotype is an adaptation to decreased lipid availability in the brain relative + to other tissues, which results in a site-specific dependency on fatty acid + synthesis for breast tumors growing at this site. Genetic or pharmacological + inhibition of fatty acid synthase (FASN) reduces HER2+ breast tumor growth + in the brain, demonstrating that differences in nutrient availability across + metastatic sites can result in targetable metabolic dependencies.", "venue": + "Neuro-Oncology Advances", "year": 2021, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://academic.oup.com/noa/article-pdf/3/Supplement_1/i7/36733750/vdab024.029.pdf", + "status": null}, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", + "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-03-01", "journal": {"volume": + "3", "pages": "i7 - i8", "name": "Neuro-oncology Advances"}, "authors": [{"authorId": + "35545769", "name": "G. Ferraro"}, {"authorId": "2157679423", "name": "A. + Ali"}, {"authorId": "114311983", "name": "Alba Luengo"}, {"authorId": "10029385", + "name": "D. Kodack"}, {"authorId": "2922270", "name": "A. Deik"}, {"authorId": + "39862913", "name": "Keene L. Abbott"}, {"authorId": "11045592", "name": "Divya + Bezwada"}, {"authorId": "29960670", "name": "L. Blanc"}, {"authorId": "4151707", + "name": "Brendan Prideaux"}, {"authorId": "2149169420", "name": "Xin Jin"}, + {"authorId": "89996372", "name": "Jessica M. Possada"}, {"authorId": "2144207912", + "name": "Jiang Chen"}, {"authorId": "2056653349", "name": "Christopher R Chin"}, + {"authorId": "10042929", "name": "Z. Amoozgar"}, {"authorId": "2067628106", + "name": "Raphael Ferreira"}, {"authorId": "19188310", "name": "Ivy X. Chen"}, + {"authorId": "5110430", "name": "K. Naxerova"}, {"authorId": "2064839498", + "name": "Christopher Ng"}, {"authorId": "115500939", "name": "Anna M. Westermark"}, + {"authorId": "40602288", "name": "M. Duquette"}, {"authorId": "5239105", "name": + "S. Roberge"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "1678407", "name": "D. Duda"}, {"authorId": "2900051", "name": "T. Golub"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3028470", "name": + "J. Asara"}, {"authorId": "34711277", "name": "Shawn M. Davidson"}, {"authorId": + "3057625", "name": "D. Fukumura"}, {"authorId": "3361348", "name": "V. Dartois"}, + {"authorId": "3633091", "name": "C. Clish"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "32514332", "name": "R. Jain"}]}, {"paperId": + "86d0fa809c754c11fe1bd8b629af606f6aa936d7", "externalIds": {"DOI": "10.1101/2021.10.01.462764", + "CorpusId": 238359345}, "corpusId": 238359345, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/86d0fa809c754c11fe1bd8b629af606f6aa936d7", + "title": "Non-conserved metabolic regulation by LKB1 distinguishes human and + mouse lung adenocarcinoma", "abstract": "KRAS is the most frequently mutated + oncogene in human lung adenocarcinomas (hLUAD) and activating mutations in + KRAS frequently co-occur with loss-of-function mutations in the tumor suppressor + genes, TP53 or STK11/LKB1. However, mutation of all three genes is rarely + observed in hLUAD, even though engineered mutations of all three genes produces + a highly aggressive lung adenocarcinoma in mice (mLUAD). Here we provide an + explanation of this difference between hLUAD and mLUAD by uncovering an evolutionary + divergence in regulation of the glycolytic enzyme triosephosphate isomerase + (TPI1). Using KRAS/TP53 mutant hLUAD cell lines, we show that TPI1 enzymatic + activity can be altered via phosphorylation at Ser21 by the Salt Inducible + Kinases (SIKs) in an LKB1-dependent manner; this allows modulation of glycolytic + flux between completion of glycolysis and production of glycerol lipids. This + metabolic flexibility appears to be critical in rapidly growing cells with + KRAS and TP53 mutations, explaining why loss of LKB1 creates a metabolic liability + in these tumors. In mice, the amino acid at position 21 of TPI1 is a Cys residue + which can be oxidized to alter TPI1 activity, allowing regulation of glycolytic + flux balance without a need for SIK kinases or LKB1. Our findings reveal an + unexpected role for TPI1 in metabolic reprogramming and suggest that LKB1 + and SIK family kinases are potential targets for treating KRAS/TP53 mutant + hLUAD. Our data also provide a cautionary example of the limits of genetically + engineered murine models as tools to study human diseases such as cancers.", + "venue": "", "year": 2021, "referenceCount": 45, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.biorxiv.org/content/biorxiv/early/2021/10/02/2021.10.01.462764.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-10-02", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "40353456", "name": "Benjamin D. Stein"}, + {"authorId": "12021693", "name": "J. Ferrarone"}, {"authorId": "123766050", + "name": "Eric E. Gardner"}, {"authorId": "77500164", "name": "Jae-won Chang"}, + {"authorId": "144790190", "name": "David Wu"}, {"authorId": "2109625387", + "name": "Qiuying Chen"}, {"authorId": "6028952", "name": "Pablo E. Hollstein"}, + {"authorId": "49059923", "name": "M. Yuan"}, {"authorId": "46875693", "name": + "R. Liang"}, {"authorId": "14394779", "name": "John S. Coukos"}, {"authorId": + "32040251", "name": "Miriam Sindelar"}, {"authorId": "5891999", "name": "B. + Ngo"}, {"authorId": "5769141", "name": "S. Gross"}, {"authorId": "4426388", + "name": "R. Shaw"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "4021080", "name": "R. Moellering"}, {"authorId": "2681217", "name": "H. Varmus"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ab43fa077d9e43a21ddb37db50fc28e5fb0195b2", + "externalIds": {"DOI": "10.1016/j.cell.2021.03.059", "CorpusId": 233247370, + "PubMed": "33861966"}, "corpusId": 233247370, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/ab43fa077d9e43a21ddb37db50fc28e5fb0195b2", + "title": "The mTORC1 pathway stimulates glutamine metabolism and cell proliferation + by repressing SIRT4", "abstract": null, "venue": "Cell", "year": 2021, "referenceCount": + 0, "citationCount": 5, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S0092867421004323/pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-04-15", "journal": {"volume": + "184", "name": "Cell"}, "authors": [{"authorId": "6688912", "name": "A. Csibi"}, + {"authorId": "46775302", "name": "S. Fendt"}, {"authorId": "49672566", "name": + "Chenggang Li"}, {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": + "32210637", "name": "A. Y. Choo"}, {"authorId": "7362234", "name": "Douglas + J. Chapski"}, {"authorId": "2112433", "name": "S. Jeong"}, {"authorId": "3765048", + "name": "J. Dempsey"}, {"authorId": "3744617", "name": "A. Parkhitko"}, {"authorId": + "4644464", "name": "T. Morrison"}, {"authorId": "4397360", "name": "E. Henske"}, + {"authorId": "6212141", "name": "M. Haigis"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}, {"authorId": + "79481462", "name": "Jane J. Yu"}, {"authorId": "4037343", "name": "J. Blenis"}]}, + {"paperId": "c9cf4243792a54c5210c260c0750c1e8e4e073b0", "externalIds": {"PubMedCentral": + "7992954", "DOI": "10.1186/s40170-021-00246-9", "CorpusId": 232353166, "PubMed": + "33762003"}, "corpusId": 232353166, "publicationVenue": {"id": "787ea3c5-4d66-450c-b13d-9f7934429b7f", + "name": "Cancer & Metabolism", "type": "journal", "alternate_names": ["Cancer + Metab", "Cancer and Metabolism", "Cancer Metab"], "issn": "2049-3002", "url": + "http://www.cancerandmetabolism.com/"}, "url": "https://www.semanticscholar.org/paper/c9cf4243792a54c5210c260c0750c1e8e4e073b0", + "title": "GLUT5 (SLC2A5) enables fructose-mediated proliferation independent + of ketohexokinase", "abstract": null, "venue": "Cancer & Metabolism", "year": + 2020, "referenceCount": 73, "citationCount": 2, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://cancerandmetabolism.biomedcentral.com/counter/pdf/10.1186/s40170-021-00246-9", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2020-07-16", "journal": + {"volume": "9", "name": "Cancer & Metabolism"}, "authors": [{"authorId": "46875693", + "name": "R. Liang"}, {"authorId": "2110994237", "name": "Samuel R Taylor"}, + {"authorId": "2046170895", "name": "Navid Nahiyaan"}, {"authorId": "2144577350", + "name": "J. Song"}, {"authorId": "47107919", "name": "Charles J Murphy"}, + {"authorId": "144901772", "name": "E. Dantas"}, {"authorId": "40857819", "name": + "Shuyuan Cheng"}, {"authorId": "2057635408", "name": "Ting-Wei Hsu"}, {"authorId": + "2058412873", "name": "Shakti Ramsamooj"}, {"authorId": "2062963678", "name": + "Rahul Grover"}, {"authorId": "4151944", "name": "Seo-Kyoung Hwang"}, {"authorId": + "5891999", "name": "B. Ngo"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4097554", "name": "K. Rhee"}, {"authorId": "145524334", "name": + "M. Goncalves"}]}, {"paperId": "cee741f6b1a98a9a65a96bb7b7a314c8eee3380c", + "externalIds": {"DOI": "10.1038/s43018-021-00283-9", "CorpusId": 242158007, + "PubMed": "35122065"}, "corpusId": 242158007, "publicationVenue": {"id": "f511c64e-b292-49b6-a819-65678fadeebb", + "name": "Nature Cancer", "type": "journal", "alternate_names": ["Nat Cancer"], + "issn": "2662-1347", "url": "https://www.nature.com/natcancer/"}, "url": "https://www.semanticscholar.org/paper/cee741f6b1a98a9a65a96bb7b7a314c8eee3380c", + "title": "Author Correction: Fatty acid synthesis is required for breast cancer + brain metastasis.", "abstract": null, "venue": "Nature Cancer", "year": 2021, + "referenceCount": 0, "citationCount": 2, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://www.nature.com/articles/s43018-021-00283-9.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-10-08", "journal": {"volume": + "2 11", "pages": "\n 1243\n ", "name": "Nature cancer"}, "authors": + [{"authorId": "35545769", "name": "G. Ferraro"}, {"authorId": "2157679423", + "name": "A. Ali"}, {"authorId": "114311983", "name": "Alba Luengo"}, {"authorId": + "10029385", "name": "D. Kodack"}, {"authorId": "2922270", "name": "A. Deik"}, + {"authorId": "39862913", "name": "Keene L. Abbott"}, {"authorId": "11045592", + "name": "Divya Bezwada"}, {"authorId": "29960670", "name": "L. Blanc"}, {"authorId": + "4151707", "name": "Brendan Prideaux"}, {"authorId": "2149169420", "name": + "Xin Jin"}, {"authorId": "40351159", "name": "J. Posada"}, {"authorId": "2144207912", + "name": "Jiang Chen"}, {"authorId": "2056653349", "name": "Christopher R Chin"}, + {"authorId": "10042929", "name": "Z. Amoozgar"}, {"authorId": "2067628106", + "name": "Raphael Ferreira"}, {"authorId": "19188310", "name": "Ivy X. Chen"}, + {"authorId": "5110430", "name": "K. Naxerova"}, {"authorId": "6294709", "name": + "Christopher Ng"}, {"authorId": "115500939", "name": "Anna M. Westermark"}, + {"authorId": "40602288", "name": "M. Duquette"}, {"authorId": "5239105", "name": + "S. Roberge"}, {"authorId": "3734755", "name": "N. Lindeman"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "2117720586", "name": "J. + Nielsen"}, {"authorId": "1456579956", "name": "D. Housman"}, {"authorId": + "1678407", "name": "D. Duda"}, {"authorId": "6207661", "name": "E. Brachtel"}, + {"authorId": "2900051", "name": "T. Golub"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "34711277", + "name": "Shawn M. Davidson"}, {"authorId": "3057625", "name": "D. Fukumura"}, + {"authorId": "3361348", "name": "V. Dartois"}, {"authorId": "3633091", "name": + "C. Clish"}, {"authorId": "32514332", "name": "R. Jain"}, {"authorId": "3804233", + "name": "M. V. Vander Heiden"}]}, {"paperId": "d13943fd02bf2527bc4f234053ab1670e43eaeb7", + "externalIds": {"DOI": "10.1101/2021.05.01.441686", "CorpusId": 233745373}, + "corpusId": 233745373, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/d13943fd02bf2527bc4f234053ab1670e43eaeb7", + "title": "Diverse Hotspot Thermal Profiling Methods Detect Phosphorylation-Dependent + Changes in Protein Stability", "abstract": "Hotspot thermal profiling (HTP) + methods utilize modified-peptide level information in order to interrogate + proteoform-specific stability inside of live cells. The first demonstration + of HTP involved the integration of phosphopeptide enrichment into a TMT-based, + single-LC separation thermal profiling workflow1. Here we present a new \u2018label-fractionate-enrich\u2019 + (LFE)-HTP method that involves high-pH reverse phase fractionation of TMT-labeled + peptides prior to phosphopeptide enrichment, followed by peptide detection + and quantitation using multi-notch LC-MS3. We find that LFE-HTP, while more + resource intensive, improves the depth and precision of (phospho)proteoform + coverage relative to the initial published HTP workflow. The fraction of detected + phosphorylation sites that are significantly perturbed in this new dataset + are consistent with those seen in our previous study, as well as those published + by others, when compared head-to-head with the same analysis pipelines. Likewise, + many \u2018hotspot\u2019 phosphorylation sites identified in our paper are + consistently reproduced by LFE-HTP as well as other modified HTP methods. + The LFE-HTP dataset contains many novel \u2018hotspot\u2019 phosphorylation + sites that regulate the stability of diverse proteins, including phosphosites + in the central glycolytic enzyme Aldolase A that are associated with monomer-to-oligomer + formation, enzymatic activity and metabolic regulation in cancer cells. Our + comparative analyses confirm that several variants of the HTP method can track + modified proteoforms in live cells to detect and prioritize PTM-dependent + changes in protein stability that may be associated with function.", "venue": + "bioRxiv", "year": 2021, "referenceCount": 20, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.biorxiv.org/content/biorxiv/early/2021/05/01/2021.05.01.441686.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-05-01", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "40353456", "name": "Benjamin D. Stein"}, + {"authorId": "50535527", "name": "Jun X Huang"}, {"authorId": "144790190", + "name": "David Wu"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4021080", "name": "R. Moellering"}]}, {"paperId": "d3a39e2f4b31947b77f8cf560ca620b32695db4d", + "externalIds": {"DOI": "10.1101/2021.09.10.459864", "CorpusId": 237495049}, + "corpusId": 237495049, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d3a39e2f4b31947b77f8cf560ca620b32695db4d", + "title": "Cysteine induces mitochondrial reductive stress in glioblastoma + through hydrogen peroxide production", "abstract": "Glucose and amino acid + metabolism are critical for glioblastoma (GBM) growth, but little is known + about the specific metabolic alterations in GBM that are targetable with FDA-approved + compounds. To investigate tumor metabolism signatures unique to GBM, we interrogated + The Cancer Genome Atlas for alterations in glucose and amino acid signatures + in GBM relative to other human cancers and found that GBM exhibits the highest + levels of cysteine and methionine pathway gene expression of 32 human cancers. + Treatment of patient-derived GBM cells with the FDA-approved cysteine compound + N-acetylcysteine (NAC) reduce GBM cell growth and mitochondrial oxygen consumption, + which was worsened by glucose starvation. Mechanistic experiments revealed + that cysteine compounds induce rapid mitochondrial H2O2 production and reductive + stress in GBM cells, an effect blocked by oxidized glutathione, thioredoxin, + and redox enzyme overexpression. These findings indicate that GBM is uniquely + susceptible to NAC-driven reductive stress and could synergize with glucose-lowering + treatments for GBM.", "venue": "", "year": 2021, "referenceCount": 80, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.biorxiv.org/content/biorxiv/early/2021/09/11/2021.09.10.459864.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-09-11", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "3913142", "name": "E. Noch"}, {"authorId": + "2065330100", "name": "L. Palma"}, {"authorId": "1716222698", "name": "I. + Yim"}, {"authorId": "27860524", "name": "D. Barnett"}, {"authorId": "2126518026", + "name": "Alexander Walsh"}, {"authorId": "4139100", "name": "B. Bhinder"}, + {"authorId": "123664542", "name": "E. Benedetti"}, {"authorId": "2067285", + "name": "J. Krumsiek"}, {"authorId": "2038115111", "name": "Justin Gurvitch"}, + {"authorId": "2126534129", "name": "Sumaiyah Khwaja"}, {"authorId": "150097652", + "name": "O. Elemento"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "da5860f1c54a497f76c8767c7f98f9392ae3d9f3", "externalIds": {"MAG": "3170169430", + "DOI": "10.21203/RS.3.RS-563743/V1", "CorpusId": 236423781}, "corpusId": 236423781, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/da5860f1c54a497f76c8767c7f98f9392ae3d9f3", + "title": "Blocking ActRIIB signaling and restoring appetite reverses cachexia + and improves survival in mice with lung cancer", "abstract": "\n The cancer + anorexia-cachexia syndrome (CACS) is a common, debilitating condition with + limited therapeutic options. The defining feature of CACS is weight loss, + which suggests a state of negative energy balance. It is unclear whether this + net reduction in energy is due solely to anorexia or if a combination of anorexia + and increased energy expenditure (EE) occurs. To address this question, we + induced lung cancer in mice and measured changes in food intake, EE, and body + composition. Mice with CACS developed reductions in food intake, spontaneous + activity, and EE. There was severe atrophy and markers of metabolic dysfunction + in the adipose and skeletal muscle tissues as compared to mice without CACS + and pair-fed wild-type mice. We used anamorelin fumarate (Ana), a ghrelin + receptor agonist, alone or in combination ActRIIB-Fc, a ligand trap for TGF-\u03b2/activin + family members, to reverse anorexia and skeletal muscle atrophy, respectively. + Ana effectively increased food intake and the combination of drugs increased + lean mass, restored spontaneous activity, and improved overall survival. These + beneficial effects were limited to female mice. Our findings suggest that + multimodal, gender-specific, therapies are needed to reverse CACS.", "venue": + "", "year": 2021, "referenceCount": 94, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/s41467-022-32135-0.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2021-05-28", "journal": {"volume": "", "name": ""}, "authors": + [{"authorId": "7706581", "name": "Andr\u00c9 L Queiroz"}, {"authorId": "2058412873", + "name": "Shakti Ramsamooj"}, {"authorId": "144901772", "name": "E. Dantas"}, + {"authorId": "25057716", "name": "E. Zunica"}, {"authorId": "46875693", "name": + "R. Liang"}, {"authorId": "2087916646", "name": "Anirudh Murthy"}, {"authorId": + "47107919", "name": "Charles J Murphy"}, {"authorId": "46415060", "name": + "Corey D. Holman"}, {"authorId": "34685572", "name": "Curtis J. Bare"}, {"authorId": + "2126874550", "name": "G. Ghahramani"}, {"authorId": "2385505", "name": "Zhidan + Wu"}, {"authorId": "144647984", "name": "D. Cohen"}, {"authorId": "4881087", + "name": "J. Kirwan"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "51224707", "name": "C. Axelrod"}, {"authorId": "145524334", "name": "M. Goncalves"}]}, + {"paperId": "dc97e05941eefbae4ee9540f9ee086354e6bffd2", "externalIds": {"PubMedCentral": + "8634575", "DOI": "10.1093/ajcn/nqab270", "CorpusId": 237493808, "PubMed": + "34515299"}, "corpusId": 237493808, "publicationVenue": {"id": "52460d26-e705-465a-b49c-92bb07e81ee0", + "name": "American Journal of Clinical Nutrition", "type": "journal", "alternate_names": + ["The American Journal of Clinical Nutrition", "Am J Clin Nutr"], "issn": + "0002-9165", "url": "http://www.ajcn.org/"}, "url": "https://www.semanticscholar.org/paper/dc97e05941eefbae4ee9540f9ee086354e6bffd2", + "title": "The carbohydrate-insulin model: a physiological perspective on the + obesity pandemic", "abstract": "ABSTRACT According to a commonly held view, + the obesity pandemic is caused by overconsumption of modern, highly palatable, + energy-dense processed foods, exacerbated by a sedentary lifestyle. However, + obesity rates remain at historic highs, despite a persistent focus on eating + less and moving more, as guided by the energy balance model (EBM). This public + health failure may arise from a fundamental limitation of the EBM itself. + Conceptualizing obesity as a disorder of energy balance restates a principle + of physics without considering the biological mechanisms that promote weight + gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes + a reversal of causal direction. According to the CIM, increasing fat deposition + in the body\u2014resulting from the hormonal responses to a high-glycemic-load + diet\u2014drives positive energy balance. The CIM provides a conceptual framework + with testable hypotheses for how various modifiable factors influence energy + balance and fat storage. Rigorous research is needed to compare the validity + of these 2 models, which have substantially different implications for obesity + management, and to generate new models that best encompass the evidence.", + "venue": "American Journal of Clinical Nutrition", "year": 2021, "referenceCount": + 171, "citationCount": 47, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://academic.oup.com/ajcn/article-pdf/114/6/1873/41395094/nqab270.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2021-09-13", "journal": + {"volume": "114", "pages": "1873 - 1885", "name": "The American Journal of + Clinical Nutrition"}, "authors": [{"authorId": "5357296", "name": "D. Ludwig"}, + {"authorId": "4471209", "name": "L. Aronne"}, {"authorId": "47518061", "name": + "A. Astrup"}, {"authorId": "144285023", "name": "R. de Cabo"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "143673144", "name": "M. Friedman"}, + {"authorId": "1703514", "name": "S. Heymsfield"}, {"authorId": "143913880", + "name": "James D. Johnson"}, {"authorId": "1756443", "name": "J. King"}, {"authorId": + "8678177", "name": "R. Krauss"}, {"authorId": "32514132", "name": "D. Lieberman"}, + {"authorId": "5951734", "name": "G. Taubes"}, {"authorId": "2054653160", "name": + "J. Volek"}, {"authorId": "47270053", "name": "E. Westman"}, {"authorId": + "5042577", "name": "W. Willett"}, {"authorId": "41183477", "name": "W. Yancy"}, + {"authorId": "4056154", "name": "C. Ebbeling"}]}, {"paperId": "e1a2d7472834d9dd1ad5be1c3c1799ecae47a531", + "externalIds": {"PubMedCentral": "7992201", "DOI": "10.1093/noajnl/vdab024.044", + "CorpusId": 232479877}, "corpusId": 232479877, "publicationVenue": {"id": + "4390a6c7-bd1a-4ccc-b9e6-e988368f95cb", "name": "Neuro-Oncology Advances", + "type": "journal", "alternate_names": ["Neuro-oncology Adv"], "issn": "2632-2498"}, + "url": "https://www.semanticscholar.org/paper/e1a2d7472834d9dd1ad5be1c3c1799ecae47a531", + "title": "DDRE-22. TARGETING SERINE SYNTHESIS IN BRAIN METASTASIS", "abstract": + "Abstract The brain environment is low in amino acids, including serine and + glycine, both of which are important for tumor growth as they are precursors + of proteins and nucleotide bases. How tumor cells overcome these conditions + to proliferate and survive in the brain is incompletely understood. Here, + we show that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the + first and rate-limiting step of glucose-derived serine synthesis, enables + brain metastasis in multiple human types and in preclinical models. Genetic + suppression and small molecule inhibition of PHGDH attenuated brain metastasis, + but not extra cranial tumors, and improved the overall survival of mice bearing + brain metastasis. These results demonstrate that the tumor nutrient microenvironment + determines tumor cell sensitivity to loss of serine synthesis pathway activity + and raise the possibility that serine synthesis inhibitors may be useful in + the treatment of brain metastases.", "venue": "Neuro-Oncology Advances", "year": + 2021, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://academic.oup.com/noa/article-pdf/3/Supplement_1/i11/36733882/vdab024.044.pdf", + "status": null}, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", + "source": "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2021-03-01", "journal": {"volume": + "3", "pages": "i11 - i11", "name": "Neuro-oncology Advances"}, "authors": + [{"authorId": "5891999", "name": "B. Ngo"}, {"authorId": "115819822", "name": + "Eugenie Kim"}, {"authorId": "1600811114", "name": "Victoria Osorio-Vasquez"}, + {"authorId": "50535810", "name": "Sophia Doll"}, {"authorId": "1600820777", + "name": "Sophia Bustraan"}, {"authorId": "46875693", "name": "R. Liang"}, + {"authorId": "114311983", "name": "Alba Luengo"}, {"authorId": "34711277", + "name": "Shawn M. Davidson"}, {"authorId": "2157679423", "name": "A. Ali"}, + {"authorId": "35545769", "name": "G. Ferraro"}, {"authorId": "26984663", "name": + "Grant M Fischer"}, {"authorId": "1600820946", "name": "Ariana Plasger"}, + {"authorId": "5734623", "name": "Vinagolu K. Rajasekhar"}, {"authorId": "4306515", + "name": "Edward R. Kastenhuber"}, {"authorId": "6108327", "name": "Roozbeh + Eskandari"}, {"authorId": "145170581", "name": "Sarah Bacha"}, {"authorId": + "49408849", "name": "Roshan K. Sriram"}, {"authorId": "3543494", "name": "S. + Bakhoum"}, {"authorId": "3579975", "name": "M. Snuderl"}, {"authorId": "10371243", + "name": "P. Cotzia"}, {"authorId": "1846047", "name": "J. Healey"}, {"authorId": + "1843680", "name": "D. Sabatini"}, {"authorId": "151477189", "name": "Drew + R. Jones"}, {"authorId": "50985038", "name": "Jean J. Zhao"}, {"authorId": + "145684949", "name": "Min Yu"}, {"authorId": "32514332", "name": "R. Jain"}, + {"authorId": "5460116", "name": "K. Keshari"}, {"authorId": "2117692562", + "name": "M. Davies"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "4586359", "name": "E. Hernando"}, {"authorId": "144979479", "name": "M. Mann"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5141475", "name": + "M. Pacold"}]}, {"paperId": "0154ddc39a5bcb8056991c828561841786d04caf", "externalIds": + {"PubMedCentral": "7607628", "MAG": "3097171810", "DOI": "10.1186/s13058-020-01354-y", + "CorpusId": 226229418, "PubMed": "33138866"}, "corpusId": 226229418, "publicationVenue": + {"id": "1290af6c-c79c-4253-8957-8db4a6069766", "name": "Breast Cancer Research", + "type": "journal", "alternate_names": ["Breast Cancer Res"], "issn": "1465-5411", + "url": "http://breast-cancer-research.com/"}, "url": "https://www.semanticscholar.org/paper/0154ddc39a5bcb8056991c828561841786d04caf", + "title": "Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, + in patients with metastatic triple-negative breast cancer", "abstract": null, + "venue": "Breast Cancer Research", "year": 2020, "referenceCount": 49, "citationCount": + 36, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2020-11-02", "journal": + {"volume": "22", "name": "Breast Cancer Research : BCR"}, "authors": [{"authorId": + "1401041241", "name": "A. Garrido-Castro"}, {"authorId": "143772689", "name": + "C. Saura"}, {"authorId": "1393643694", "name": "R. Barroso-Sousa"}, {"authorId": + "143887802", "name": "Hao Guo"}, {"authorId": "4316212", "name": "E. Ciruelos"}, + {"authorId": "144441047", "name": "B. Bermejo"}, {"authorId": "1901703", "name": + "J. Gavil\u00e1"}, {"authorId": "49229190", "name": "V. Serra"}, {"authorId": + "145594197", "name": "A. Prat"}, {"authorId": "3372070", "name": "L. Par\u00e9"}, + {"authorId": "145716996", "name": "P. C\u00e9liz"}, {"authorId": "152815847", + "name": "P. Villagrasa"}, {"authorId": "2111151410", "name": "Yisheng Li"}, + {"authorId": "37392807", "name": "J. Savoie"}, {"authorId": "47047818", "name": + "Zhan Xu"}, {"authorId": "2057460", "name": "C. Arteaga"}, {"authorId": "2101923", + "name": "I. Krop"}, {"authorId": "2344124", "name": "D. Solit"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2369378", "name": "E. Winer"}, {"authorId": "35141217", "name": + "N. Lin"}, {"authorId": "143607446", "name": "J. Rod\u00f3n"}]}, {"paperId": + "0a0032872553b2783d774418c075815e3605b2fb", "externalIds": {"DOI": "10.1016/j.cmet.2020.12.005", + "CorpusId": 229692208, "PubMed": "33357456"}, "corpusId": 229692208, "publicationVenue": + {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", "name": "Cell Metabolism", + "type": "journal", "alternate_names": ["Cell Metab"], "issn": "1550-4131", + "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": ["http://www.sciencedirect.com/science/journal/15504131", + "http://www.cellmetabolism.org/"]}, "url": "https://www.semanticscholar.org/paper/0a0032872553b2783d774418c075815e3605b2fb", + "title": "High Fructose Drives the Serine Synthesis Pathway in Acute Myeloid + Leukemic Cells.", "abstract": null, "venue": "Cell Metabolism", "year": 2020, + "referenceCount": 58, "citationCount": 14, "influentialCitationCount": 0, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1550413120306604/pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2020-12-17", "journal": + {"name": "Cell metabolism"}, "authors": [{"authorId": "3583062", "name": "Sangmoo + Jeong"}, {"authorId": "9567228", "name": "A. Savino"}, {"authorId": "6734378", + "name": "Rachel Chirayil"}, {"authorId": "1744766868", "name": "Ersilia Barin"}, + {"authorId": "50860020", "name": "Yuanming Cheng"}, {"authorId": "120425242", + "name": "Sun-Mi Park"}, {"authorId": "153666453", "name": "Alexandria Schurer"}, + {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "152500082", "name": "M. Kharas"}, {"authorId": + "5460116", "name": "K. Keshari"}]}, {"paperId": "1e64ffd0b17e1d16151e185cdd76ac1a571db2d6", + "externalIds": {"MAG": "3021120315", "DOI": "10.1101/2020.05.05.079095", "CorpusId": + 218571941, "PubMed": "32511403"}, "corpusId": 218571941, "publicationVenue": + {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": "bioRxiv", "type": + "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/1e64ffd0b17e1d16151e185cdd76ac1a571db2d6", + "title": "Identification of Candidate COVID-19 Therapeutics using hPSC-derived + Lung Organoids", "abstract": "The SARS-CoV-2 virus has caused already over + 3.5 million COVID-19 cases and 250,000 deaths globally. There is an urgent + need to create novel models to study SARS-CoV-2 using human disease-relevant + cells to understand key features of virus biology and facilitate drug screening. + As primary SARS-CoV-2 infection is respiratory-based, we developed a lung + organoid model using human pluripotent stem cells (hPSCs) that could be adapted + for drug screens. The lung organoids, particularly aveolar type II cells, + express ACE2 and are permissive to SARS-CoV-2 infection. Transcriptomic analysis + following SARS-CoV-2 infection revealed a robust induction of chemokines and + cytokines with little type I/III interferon signaling, similar to that observed + amongst human COVID-19 pulmonary infections. We performed a high throughput + screen using hPSC-derived lung organoids and identified FDA-approved drug + candidates, including imatinib and mycophenolic acid, as inhibitors of SARS-CoV-2 + entry. Pre- or post-treatment with these drugs at physiologically relevant + levels decreased SARS-CoV-2 infection of hPSC-derived lung organoids. Together, + these data demonstrate that hPSC-derived lung cells infected by SARS-CoV-2 + can model human COVID-19 disease and provide a valuable resource to screen + for FDA-approved drugs that might be repurposed and should be considered for + COVID-19 clinical trials.", "venue": "bioRxiv", "year": 2020, "referenceCount": + 38, "citationCount": 93, "influentialCitationCount": 4, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2020-05-05", "journal": {"name": "bioRxiv"}, "authors": [{"authorId": "1678087048", + "name": "Yuling Han"}, {"authorId": "1733349662", "name": "Liuliu Yang"}, + {"authorId": "8121194", "name": "Xiaohua Duan"}, {"authorId": "8751560", "name": + "Fuyu Duan"}, {"authorId": "1422205499", "name": "Benjamin E. Nilsson-Payant"}, + {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": "152702655", + "name": "Pengfei Wang"}, {"authorId": "1687775322", "name": "Xuming Tang"}, + {"authorId": "40543563", "name": "Tuo Zhang"}, {"authorId": "2186108428", + "name": "Zeping Zhao"}, {"authorId": "4785493", "name": "Y. Bram"}, {"authorId": + "1682800", "name": "D. Redmond"}, {"authorId": "145731038", "name": "S. Houghton"}, + {"authorId": "50652368", "name": "Duc-Huy T. Nguyen"}, {"authorId": "48207902", + "name": "Dong-Li Xu"}, {"authorId": "2144803226", "name": "Xing Wang"}, {"authorId": + "88725738", "name": "S. Uhl"}, {"authorId": "2108678622", "name": "Yaoxing + Huang"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "118390923", "name": "J. Xiang"}, {"authorId": "2113635227", "name": "Hui + Wang"}, {"authorId": "34160280", "name": "F. C. Pan"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "5462120", "name": "B. tenOever"}, {"authorId": + "144705651", "name": "D. Ho"}, {"authorId": "144263094", "name": "T. Evans"}, + {"authorId": "46462360", "name": "R. Schwartz"}, {"authorId": "2145302790", + "name": "H. Chen"}, {"authorId": "47336157", "name": "Shuibing Chen"}]}, {"paperId": + "2808e4458bedf8bbe953c5bbce8ae90ac0ce9e79", "externalIds": {"MAG": "3005914208", + "DOI": "10.1158/1538-7445.SABCS19-GS6-06", "CorpusId": 213426689}, "corpusId": + 213426689, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/2808e4458bedf8bbe953c5bbce8ae90ac0ce9e79", + "title": "Abstract GS6-06: A neoadjuvant trial with letrozole identifiesPRR11in + the 17q23 amplicon as a mechanism of resistance to endocrine therapy in ER-positive + breast cancer", "abstract": "Although the 17q23 amplicon has been associated + with luminal B breast cancer (BC) and high risk of recurrence, a specific + gene or genes in this region that would be causal to endocrine resistance + have not yet been uncovered. We performed whole transcriptome analysis on + RNA extracted from 58 estrogen receptor (ER)+ BCs treated with neoadjuvant + letrozole for median 7.2 months. PRR11 (Proline rich 11), located in 17q23, + was upregulated in non-responding tumors as defined by relapse after a median + follow up of 5 years and/or a preoperative endocrine prognostic index (PEPI) + \u22654. Differential gene expression analysis between tumors expressing low + vs high PRR11 mRNA showed that BC signatures associated with proliferation, + IGF-1 and PI3K signaling were enriched in tumors with high PRR11 expression. + Rate of PRR11 amplification is 15.2% in the Metastatic Breast Cancer project, + but 9.5% and 9.4% in METABRIC and The Cancer Genome Atlas (TCGA), respectively. + Gene Set Enrichment Analysis revealed an enrichment of hallmark gene sets + associated with proliferation in PRR11-amplified ER+ BCs in METABRIC and TCGA. + Integrated analysis of gene expression with on-treatment Ki67 levels from + three independent studies with operable ER+ BCs treated with neoadjuvant aromatase + inhibitor (ACOSOG-Z1031, NCT00651976, Llombart-Cussac et al.) showed that + PRR11 was the only gene in 17q23 with a significant correlation with a high + Ki67 levels across all studies. PRR11 knockdown inhibited E2-independent growth + of HCC1428 LTED (long-term estrogen deprived) and MCF7 LTED cells in culture + and MCF7 xenografts. PRR11 siRNA also inhibited growth of fulvestrant-resistant + and tamoxifen-resistant MCF7 cells. Conversely, PRR11 transduction induced + MDA-MB-134VI cell growth under estrogen-depleted conditions. Using a PCR array + with 84-cell cycle genes, we identified SKP2, CDKN1A, CCNB2, CCNA2, CKS2 and + CCNB1 as genes downregulated by PRR11 knockdown. Except for SKP2 and CDKN1A, + expression of all those genes was elevated in PRR11-amplifiedER+ BCs in TCGA + and METABRIC. Suggesting a link to activation of PI3K signaling, we found + the proline-rich motif of PRR11 associates with the SH3 domain of the p85 + regulatory subunit of PI3K. We hypothesized that this association suppresses + p85 homodimer formation, thus facilitating binding of PI3K\u03b1 (p110\u03b1)-p85 + dimers to IRS1, retention of p110\u03b1 at the plasma membrane and, hence, + activation of PI3K/AKT. To test this, we co-transfected HEK293T cells with + HA-p85 and FLAG-p85. Forced expression of PRR11 reduced HA-p85 and FLAG-p85 + homodimers as shown by HA and FLAG pulldowns followed by FLAG and HA immunoblots, + respectively. PRR11 overexpression enhanced insulin-stimulated association + of IRS1 to p110\u03b1 and activation of AKT. PRR11 knockdown reduced insulin/IGF-1/2-stimulated + p-AKT. In METABRIC and TCGA, PRR11 amplification and PIK3CA mutations are + exclusive of each other, suggesting these alterations would be functionally + linked with the same pathway. Connectivity map analysis with the list of genes + significantly overexpressed in ER+/PRR11-amplified BCs predicted PI3K inhibitors + as perturbations that suppress such gene list. In the MGH/Sanger dataset, + PRR11-amplified BC cell lines displayed significantly higher sensitivity to + the pan-PI3K inhibitor pictilisib compared to cell lines without PRR11 amplification. + Finally, inhibition of PI3K\u03b1 by siRNA or alpelisib abrogated E2-independent + growth and insulin-stimulated growth of PRR11-transduced MDA-MB-134VI and + MCF10A cells, respectively, suggesting p110\u03b1 is required for the growth + promoting effects of PRR11. These data suggest that 1) PRR11 is a mediator + of resistance to antiestrogens via amplification of PI3K/AKT signaling, and + 2) PI3K\u03b1 is a potential therapeutic target in ER+ BCs harboring PRR11 + amplification. Citation Format: Kyung-min Lee, Angel Guerrero-Zotano, Ariella + Hanker, Alberto Servetto, Dhivya Sudhan, Luigi Formisano, Valerie Jansen, + Paula Gonzalez-Ericsson, Melinda Sanders, Thomas Stricker, Lewis Cantley, + Carlos Arteaga. A neoadjuvant trial with letrozole identifies PRR11 in the + 17q23 amplicon as a mechanism of resistance to endocrine therapy in ER-positive + breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer + Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer + Res 2020;80(4 Suppl):Abstract nr GS6-06.", "venue": "", "year": 2020, "referenceCount": + 0, "citationCount": 2, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2020-02-15", "journal": {"volume": + "80", "name": "Cancer Research"}, "authors": [{"authorId": "46542827", "name": + "Kyung-Min Lee"}, {"authorId": "1403641116", "name": "A. Guerrero-Zotano"}, + {"authorId": "5872582", "name": "Ariella B. Hanker"}, {"authorId": "5294693", + "name": "A. Servetto"}, {"authorId": "6577378", "name": "Dhivya R. Sudhan"}, + {"authorId": "40940752", "name": "L. Formisano"}, {"authorId": "144653026", + "name": "V. Jansen"}, {"authorId": "1400994437", "name": "P. Gonzalez-Ericsson"}, + {"authorId": "46945931", "name": "M. Sanders"}, {"authorId": "47705275", "name": + "T. Stricker"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2057460", "name": "C. Arteaga"}]}, {"paperId": "2f2aec0810029f6092d759307cd22fd4fe473dff", + "externalIds": {"MAG": "3082144895", "DOI": "10.1038/s41588-020-0701-7", "CorpusId": + 221496182, "PubMed": "32884149"}, "corpusId": 221496182, "publicationVenue": + {"id": "bb27e645-e57c-42c3-bcbc-c7b443c58209", "name": "Nature Genetics", + "type": "journal", "alternate_names": ["Nat Genet"], "issn": "1061-4036", + "url": "http://www.nature.com/ng/", "alternate_urls": ["http://www.nature.com/ng/index.html"]}, + "url": "https://www.semanticscholar.org/paper/2f2aec0810029f6092d759307cd22fd4fe473dff", + "title": "Author Correction: A co-clinical approach identifies mechanisms + and potential therapies for androgen deprivation resistance in prostate cancer", + "abstract": null, "venue": "Nature Genetics", "year": 2020, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.nature.com/articles/s41588-020-0701-7.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2020-09-03", "journal": {"volume": "52", "pages": + "1132", "name": "Nature Genetics"}, "authors": [{"authorId": "5729169", "name": + "A. Lunardi"}, {"authorId": "2901501", "name": "U. Ala"}, {"authorId": "4276612", + "name": "M. Epping"}, {"authorId": "6316033", "name": "L. Salmena"}, {"authorId": + "4102988", "name": "J. Clohessy"}, {"authorId": "4817196", "name": "Kaitlyn + A. Webster"}, {"authorId": "47227159", "name": "Guocan Wang"}, {"authorId": + "3778026", "name": "R. Mazzucchelli"}, {"authorId": "144862941", "name": "M. + Bianconi"}, {"authorId": "5592639", "name": "E. Stack"}, {"authorId": "50267670", + "name": "R. Lis"}, {"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5854981", "name": "G. Bubley"}, + {"authorId": "13870598", "name": "C. Cordon-Cardo"}, {"authorId": "3950794", + "name": "W. Gerald"}, {"authorId": "145421680", "name": "R. Montironi"}, {"authorId": + "7505152", "name": "S. Signoretti"}, {"authorId": "6213932", "name": "M. Loda"}, + {"authorId": "3547827", "name": "C. Nardella"}, {"authorId": "4499580", "name": + "P. Pandolfi"}]}, {"paperId": "37e5c491fe8335b24dae149954c4ad5fc5e41b52", + "externalIds": {"MAG": "3089217892", "DOI": "10.1016/j.annonc.2020.08.1346", + "CorpusId": 225275236}, "corpusId": 225275236, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/37e5c491fe8335b24dae149954c4ad5fc5e41b52", + "title": "1954P A pan-cancer analysis of double PIK3CA mutations", "abstract": + null, "venue": "", "year": 2020, "referenceCount": 0, "citationCount": 1, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.annalsofoncology.org/article/S0923753420413420/pdf", "status": + null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2020-09-01", "journal": {"volume": + "31", "name": "Annals of Oncology"}, "authors": [{"authorId": "35123724", + "name": "N. Vasan"}, {"authorId": "40088390", "name": "S. Sivakumar"}, {"authorId": + "3287834", "name": "D. Jin"}, {"authorId": "2169319444", "name": "J. Ross"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "8336319", "name": + "M. Scaltriti"}, {"authorId": "48156320", "name": "E. Sokol"}]}, {"paperId": + "3b7575f733f5972bc3dfd07d5f3ba8f3cf1b38ee", "externalIds": {"MAG": "3010473282", + "DOI": "10.1016/j.chembiol.2020.02.003", "CorpusId": 212417732, "PubMed": + "32130941"}, "corpusId": 212417732, "publicationVenue": {"id": "66a2a80a-90f1-4c5a-8798-1be97c318574", + "name": "Cell Chemical Biology", "alternate_names": ["Cell Chem Biology"], + "issn": "2451-9456", "alternate_issns": ["2451-9448"], "url": "https://www.sciencedirect.com/journal/cell-chemical-biology", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/24519456", + "http://www.sciencedirect.com/science/journal/24519456/23/"]}, "url": "https://www.semanticscholar.org/paper/3b7575f733f5972bc3dfd07d5f3ba8f3cf1b38ee", + "title": "Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent + Inhibitors.", "abstract": null, "venue": "Cell Chemical Biology", "year": + 2020, "referenceCount": 59, "citationCount": 21, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S2451945620300672/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2020-03-03", "journal": {"name": "Cell + chemical biology"}, "authors": [{"authorId": "6443517", "name": "S. Sivakumaren"}, + {"authorId": "13574443", "name": "Hyeseok Shim"}, {"authorId": "2262535", + "name": "Tinghu Zhang"}, {"authorId": "11404167", "name": "F. M. Ferguson"}, + {"authorId": "49142390", "name": "Mark R. Lundquist"}, {"authorId": "39374687", + "name": "Christopher M Browne"}, {"authorId": "91486080", "name": "H. Seo"}, + {"authorId": "4422893", "name": "M. Paddock"}, {"authorId": "16018077", "name": + "Theresa D. Manz"}, {"authorId": "7864101", "name": "Baishan Jiang"}, {"authorId": + "11796890", "name": "Mingfeng Hao"}, {"authorId": "50822194", "name": "P. + Krishnan"}, {"authorId": "152325571", "name": "Diana G. Wang"}, {"authorId": + "2115865796", "name": "T. Yang"}, {"authorId": "6254222", "name": "Nicholas + Kwiatkowski"}, {"authorId": "2297254", "name": "S. Ficarro"}, {"authorId": + "36406440", "name": "J. Cunningham"}, {"authorId": "2605597", "name": "J. + Marto"}, {"authorId": "1400570681", "name": "S. Dhe-Paganon"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3977406", "name": "N. Gray"}]}, + {"paperId": "3fd887bbf1178f1ced49551888df37abe245b09b", "externalIds": {"MAG": + "3113241844", "DOI": "10.1101/2020.08.14.251207", "CorpusId": 229549364}, + "corpusId": 229549364, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/3fd887bbf1178f1ced49551888df37abe245b09b", + "title": "The FDA-approved drug Alectinib compromises SARS-CoV-2 nucleocapsid + phosphorylation and inhibits viral infection in vitro", "abstract": "While + vaccines are vital for preventing COVID-19 infections, it is critical to develop + new therapies to treat patients who become infected. Pharmacological targeting + of a host factor required for viral replication can suppress viral spread + with a low probability of viral mutation leading to resistance. In particular, + host kinases are highly druggable targets and a number of conserved coronavirus + proteins, notably the nucleoprotein (N), require phosphorylation for full + functionality. In order to understand how targeting kinases could be used + to compromise viral replication, we used a combination of phosphoproteomics + and bioinformatics as well as genetic and pharmacological kinase inhibition + to define the enzymes important for SARS-CoV-2 N protein phosphorylation and + viral replication. From these data, we propose a model whereby SRPK1/2 initiates + phosphorylation of the N protein, which primes for further phosphorylation + by GSK-3\u03b1/\u03b2 and CK1 to achieve extensive phosphorylation of the + N protein SR-rich domain. Importantly, we were able to leverage our data to + identify an FDA-approved kinase inhibitor, Alectinib, that suppresses N phosphorylation + by SRPK1/2 and limits SARS-CoV-2 replication. Together, these data suggest + that repurposing or developing novel host-kinase directed therapies may be + an efficacious strategy to prevent or treat COVID-19 and other coronavirus-mediated + diseases.", "venue": "", "year": 2020, "referenceCount": 148, "citationCount": + 27, "influentialCitationCount": 3, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2020-08-14", "journal": {"volume": "", "name": "bioRxiv"}, + "authors": [{"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": + "38692984", "name": "B. Heaton"}, {"authorId": "32603328", "name": "T. Levy"}, + {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": "145658521", + "name": "Tristan X. Jordan"}, {"authorId": "2055611292", "name": "B. M. Cohen"}, + {"authorId": "14658204", "name": "A. Kerelsky"}, {"authorId": "144181325", + "name": "Ting-Yu Lin"}, {"authorId": "51910553", "name": "Katarina M Liberatore"}, + {"authorId": "1931600430", "name": "Danielle K Bulaon"}, {"authorId": "4306515", + "name": "Edward R. Kastenhuber"}, {"authorId": "2042047500", "name": "Marisa + N Mercadante"}, {"authorId": "2042286049", "name": "Kripa Shobana-Ganesh"}, + {"authorId": "2109324253", "name": "Long He"}, {"authorId": "46462360", "name": + "R. Schwartz"}, {"authorId": "47336157", "name": "Shuibing Chen"}, {"authorId": + "50028113", "name": "H. Weinstein"}, {"authorId": "1513334045", "name": "O. + Elemento"}, {"authorId": "6016224", "name": "E. Piskounova"}, {"authorId": + "1422205499", "name": "Benjamin E. Nilsson-Payant"}, {"authorId": "2123198", + "name": "Gina Lee"}, {"authorId": "66419419", "name": "Joseph D. Trimarco"}, + {"authorId": "2042240908", "name": "Kaitlyn N Burke"}, {"authorId": "30094094", + "name": "Cait E. Hamele"}, {"authorId": "6181769", "name": "Ryan R. Chaparian"}, + {"authorId": "16048806", "name": "Alfred T. Harding"}, {"authorId": "47203895", + "name": "Aleksandra Tata"}, {"authorId": "8361947", "name": "Xinyu Zhu"}, + {"authorId": "38101990", "name": "P. Tata"}, {"authorId": "2110209555", "name": + "Clare M. Smith"}, {"authorId": "6536164", "name": "A. Possemato"}, {"authorId": + "48769916", "name": "S. Tkachev"}, {"authorId": "46627576", "name": "P. Hornbeck"}, + {"authorId": "4424720", "name": "S. Beausoleil"}, {"authorId": "48361643", + "name": "Shankara K. Anand"}, {"authorId": "48975912", "name": "F. Aguet"}, + {"authorId": "2110594", "name": "G. Getz"}, {"authorId": "35178796", "name": + "A. Davidson"}, {"authorId": "4107601", "name": "K. Heesom"}, {"authorId": + "2042810306", "name": "M. Kavanagh-Williamson"}, {"authorId": "145133405", + "name": "D. Matthews"}, {"authorId": "5462120", "name": "B. tenOever"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4037343", "name": "J. Blenis"}, + {"authorId": "35057532", "name": "N. Heaton"}]}, {"paperId": "44afbde776b7519a22a73725a55c07ffc36e418b", + "externalIds": {"MAG": "3013488946", "DOI": "10.1158/1538-7445.sabcs19-p3-03-01", + "CorpusId": 216169805}, "corpusId": 216169805, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/44afbde776b7519a22a73725a55c07ffc36e418b", + "title": "Abstract P3-03-01: DoublePIK3CAmutations incisdrive oncogene addiction + and enhance sensitivity to PI3K alpha inhibitors in breast cancer", "abstract": + "Activating mutations in PIK3CA, the gene coding for the catalytic subunit + (p110\u03b1) of phosphoinositide-3-kinase (PI3K), are the most frequent oncogenic + alterations in estrogen receptor-positive (ER+) breast cancer and are also + prevalent in other tumor types. PI3K\u03b1 inhibitors including alpelisib + have recently been shown to be clinically active in ER+ PIK3CA mutant breast + cancer. To characterize determinants of sensitivity to these agents, we undertook + a comprehensive analysis of PIK3CA mutant cancer genomes and observed the + presence of double PIK3CA mutations in 12-15% of breast cancer and other tumor + types. These double PIK3CA mutations are clonal, located in cis on the same + allele, and are composed of a single hotspot mutation combined with a recurrent + second-site mutation. Double PIK3CA mutations in cis result in increased PI3K + activity and downstream signaling together with enhanced cell proliferation + and tumor growth compared to single hotspot mutations. The biochemical mechanisms + underlying this increased oncogenicity include increased disruption of p110\u03b1 + binding to the inhibitory subunit p85\u03b1, which relieves its catalytic + inhibition, and increased membrane lipid binding. Finally, these double PIK3CA + mutations predict for increased sensitivity to PI3K\u03b1 inhibitors compared + to single hotspot mutations (e.g. E545K or H1047R) in experimental models + and in patients with ER+ PIK3CA mutant metastatic breast cancer from the SANDPIPER + randomized phase III clinical trial. These findings implicate double PIK3CA + mutations in cis as a novel mechanism of oncogene addiction relative to single + hotspot mutations, providing a rationale to develop PI3K\u03b1 inhibitors + for the therapy of double PIK3CA mutant cancers. Citation Format: Neil Vasan, + Pedram Razavi, Jared L Johnson, Hong Shao, Timothy Wilson, Frauke Schimmoller, + Hardik Shah, Alesia Antoine, Erik Ladewig, Alexander Gorelick, Ting-Yu Lin, + Eneda Toska, Guotai Xu, Abiha Kazmi, Matthew T Chang, Barry S. Taylor, Maura + N. Dickler, Komal Jhaveri, Sarat Chandarlapaty, Raul Rabadan, Ed Reznik, Melissa + L Smith, Robert Sebra, Lori Friedman, Lewis C Cantley, Maurizio Scaltriti, + Jose Baselga. Double PIK3CA mutations in cis drive oncogene addiction and + enhance sensitivity to PI3K alpha inhibitors in breast cancer [abstract]. + In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec + 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract + nr P3-03-01.", "venue": "", "year": 2020, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2020-02-15", "journal": {"volume": + "80", "name": "Cancer Research"}, "authors": [{"authorId": "35123724", "name": + "N. Vasan"}, {"authorId": "3224289", "name": "P. Razavi"}, {"authorId": "145916288", + "name": "Jared L. Johnson"}, {"authorId": "2959236", "name": "H. Shao"}, {"authorId": + "2017652", "name": "T. Wilson"}, {"authorId": "5323777", "name": "F. Schimmoller"}, + {"authorId": "49820132", "name": "H. Shah"}, {"authorId": "49335811", "name": + "Alesia Antoine"}, {"authorId": "3139198", "name": "Erik Ladewig"}, {"authorId": + "48892954", "name": "A. Gorelick"}, {"authorId": "144181325", "name": "Ting-Yu + Lin"}, {"authorId": "4733908", "name": "E. Toska"}, {"authorId": "51290929", + "name": "Guotai Xu"}, {"authorId": "150907238", "name": "Abiha Kazmi"}, {"authorId": + "2141904248", "name": "Matthew T. Chang"}, {"authorId": "36898514", "name": + "B. Taylor"}, {"authorId": "4713308", "name": "M. Dickler"}, {"authorId": + "47352468", "name": "K. Jhaveri"}, {"authorId": "6037809", "name": "S. Chandarlapaty"}, + {"authorId": "40620158", "name": "R. Rabad\u00e1n"}, {"authorId": "145632788", + "name": "E. Reznik"}, {"authorId": "2116670076", "name": "M. Smith"}, {"authorId": + "46517710", "name": "R. Sebra"}, {"authorId": "48530297", "name": "L. Friedman"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "8336319", "name": + "M. Scaltriti"}, {"authorId": "144806171", "name": "J. Baselga"}]}, {"paperId": + "6fbfc199c9508fc0a7f113a6b5477ac4ff463476", "externalIds": {"MAG": "3009258273", + "DOI": "10.1038/s41574-020-0329-9", "CorpusId": 211836188, "PubMed": "32127696"}, + "corpusId": 211836188, "publicationVenue": {"id": "72983286-4c30-4ba6-b32a-33fb49586d6e", + "name": "Nature Reviews Endocrinology", "type": "journal", "alternate_names": + ["Nat Rev Endocrinol"], "issn": "1759-5029", "url": "http://www.nature.com/nrendo/", + "alternate_urls": ["http://www.nature.com/nrendo/index.html"]}, "url": "https://www.semanticscholar.org/paper/6fbfc199c9508fc0a7f113a6b5477ac4ff463476", + "title": "Insulin\u2013PI3K signalling: an evolutionarily insulated metabolic + driver of cancer", "abstract": null, "venue": "Nature Reviews Endocrinology", + "year": 2020, "referenceCount": 105, "citationCount": 90, "influentialCitationCount": + 4, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "2020-03-03", "journal": {"volume": "16", "pages": "276-283", + "name": "Nature Reviews Endocrinology"}, "authors": [{"authorId": "48821307", + "name": "B. Hopkins"}, {"authorId": "145524334", "name": "M. Goncalves"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "7bc2772d879dea17c95f1a78285eabedf6c65c76", + "externalIds": {"MAG": "3016653743", "DOI": "10.1021/acs.jmedchem.0c00227", + "CorpusId": 215802532, "PubMed": "32298120"}, "corpusId": 215802532, "publicationVenue": + {"id": "4cce60a8-2106-4240-bece-fb6488df6bd1", "name": "Journal of Medicinal + Chemistry", "type": "journal", "alternate_names": ["J Med Chem"], "issn": + "0022-2623", "url": "https://pubs.acs.org/journal/jmcmar", "alternate_urls": + ["http://pubs.acs.org/journal/jmcmar", "http://pubs.acs.org/journals/jmcmar/index.html"]}, + "url": "https://www.semanticscholar.org/paper/7bc2772d879dea17c95f1a78285eabedf6c65c76", + "title": "Discovery and Structure-Activity Relationship Study of (Z)-5-Methylenethiazolidin-4-one + Derivatives as Potent and Selective Pan-phosphatidylinositol 5-Phosphate 4-Kinase + Inhibitors.", "abstract": "Due to their role in many important signaling pathways, + phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are attractive targets + for the development of experimental therapeutics for cancer, metabolic and + immunological disorders. Recent efforts to develop small molecule inhibitors + for these lipid kinases resulted in compounds with low- to sub-micromolar + potencies. Here, we report the identification of CVM-05-002 using a high-throughput + screen of PI5P4K\u03b1 against our in-house kinase inhibitor library. CVM-05-002 + is a potent and selective inhibitor of PI5P4Ks and a 1.7 \u00c5 X-ray structure + reveals its binding interactions in the ATP-binding pocket. Further investigation + of the structure-activity relationship led to the development of compound + 13, replacing the rhodanine-like moiety present in CVM-05-002 with an indole, + a potent pan-PI5P4K inhibitor with excellent kinome-wide selectivity. Finally, + we employed isothermal cellular thermal shift assays (CETSAs) to demonstrate + effective cellular target engagement of PI5P4K\u03b1 and -\u03b2 by the inhibitors + in HEK 293T cells.", "venue": "Journal of Medicinal Chemistry", "year": 2020, + "referenceCount": 45, "citationCount": 13, "influentialCitationCount": 0, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2020-04-16", "journal": {"name": "Journal + of medicinal chemistry"}, "authors": [{"authorId": "16018077", "name": "Theresa + D. Manz"}, {"authorId": "6443517", "name": "S. Sivakumaren"}, {"authorId": + "11404167", "name": "F. M. Ferguson"}, {"authorId": "2262535", "name": "Tinghu + Zhang"}, {"authorId": "6707118", "name": "Adam Yasgar"}, {"authorId": "91486080", + "name": "H. Seo"}, {"authorId": "2297254", "name": "S. Ficarro"}, {"authorId": + "5223652", "name": "Joseph D. Card"}, {"authorId": "13574443", "name": "Hyeseok + Shim"}, {"authorId": "5861054", "name": "Chandrasekhar V. Miduturu"}, {"authorId": + "145183304", "name": "A. Simeonov"}, {"authorId": "145829790", "name": "M. + Shen"}, {"authorId": "2605597", "name": "J. Marto"}, {"authorId": "1400570681", + "name": "S. Dhe-Paganon"}, {"authorId": "143999402", "name": "M. Hall"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3977406", "name": "N. Gray"}]}, + {"paperId": "7c7cd2df56ea3c778bae9b69142bf284398a036d", "externalIds": {"PubMedCentral": + "7599336", "MAG": "3097576427", "DOI": "10.1038/s41467-020-19291-x", "CorpusId": + 226219046, "PubMed": "33127913"}, "corpusId": 226219046, "publicationVenue": + {"id": "43b3f0f9-489a-4566-8164-02fafde3cd98", "name": "Nature Communications", + "type": "journal", "alternate_names": ["Nat Commun"], "issn": "2041-1723", + "url": "https://www.nature.com/ncomms/", "alternate_urls": ["http://www.nature.com/ncomms/about/index.html", + "http://www.nature.com/ncomms/index.html"]}, "url": "https://www.semanticscholar.org/paper/7c7cd2df56ea3c778bae9b69142bf284398a036d", + "title": "Proline rich 11 (PRR11) overexpression amplifies PI3K signaling + and promotes antiestrogen resistance in breast cancer", "abstract": null, + "venue": "Nature Communications", "year": 2020, "referenceCount": 60, "citationCount": + 17, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/s41467-020-19291-x.pdf", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2020-10-30", "journal": {"volume": "11", "name": "Nature + Communications"}, "authors": [{"authorId": "46542827", "name": "Kyung-Min + Lee"}, {"authorId": "1403641116", "name": "A. Guerrero-Zotano"}, {"authorId": + "5294693", "name": "A. Servetto"}, {"authorId": "6577378", "name": "Dhivya + R. Sudhan"}, {"authorId": "123260589", "name": "Chang-Ching Lin"}, {"authorId": + "40940752", "name": "L. Formisano"}, {"authorId": "144653026", "name": "V. + Jansen"}, {"authorId": "1400994437", "name": "P. Gonzalez-Ericsson"}, {"authorId": + "46945931", "name": "M. Sanders"}, {"authorId": "47705275", "name": "T. Stricker"}, + {"authorId": "2445482", "name": "G. Raj"}, {"authorId": "2084800", "name": + "K. Dean"}, {"authorId": "50572665", "name": "R. Fiolka"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "5872582", "name": "Ariella B. Hanker"}, + {"authorId": "2057460", "name": "C. Arteaga"}]}, {"paperId": "873b1457f2251650f556603b81cf77bd0d3e1274", + "externalIds": {"PubMedCentral": "7608751", "MAG": "3093156639", "DOI": "10.1101/gad.341545.120", + "CorpusId": 222835739, "PubMed": "33060135"}, "corpusId": 222835739, "publicationVenue": + {"id": "94df828d-8411-48df-8aec-f13101ebb8f4", "name": "Genes & Development", + "type": "journal", "alternate_names": ["Gene Dev"], "issn": "0890-9369", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=101", "alternate_urls": + ["http://www.genesdev.org/", "http://genesdev.cshlp.org/"]}, "url": "https://www.semanticscholar.org/paper/873b1457f2251650f556603b81cf77bd0d3e1274", + "title": "Selective inhibition of CDK7 reveals high-confidence targets and + new models for TFIIH function in transcription", "abstract": "In this study, + Rimel et al. set out to investigate the roles of CDK7 in transcription. Using + SILAC-based phosphoproteomics with transcriptomics and biochemical assays, + the authors identified high-confidence CDK7 substrates, a surprisingly widespread + requirement for CDK7 activity in splicing, and unexpected aspects of CDK7 + kinase regulation that involve its association with TFIIH.", "venue": "Genes + & Development", "year": 2020, "referenceCount": 82, "citationCount": 37, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "http://genesdev.cshlp.org/content/34/21-22/1452.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2020-10-15", "journal": {"volume": + "34", "pages": "1452 - 1473", "name": "Genes & Development"}, "authors": [{"authorId": + "46200980", "name": "Jenna K. Rimel"}, {"authorId": "6748388", "name": "Zachary + Poss"}, {"authorId": "47130731", "name": "Benjamin Erickson"}, {"authorId": + "1581339333", "name": "Zachary L Maas"}, {"authorId": "5254479", "name": "Christopher + C. Ebmeier"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "144829833", "name": "T. Decker"}, {"authorId": "5247030", "name": "Tomer + M. Yaron"}, {"authorId": "49651964", "name": "M. Bradley"}, {"authorId": "47246659", + "name": "Kristin B Hamman"}, {"authorId": "10193089", "name": "Shanhu Hu"}, + {"authorId": "3743925", "name": "G. Malojcic"}, {"authorId": "4705135", "name": + "J. Marineau"}, {"authorId": "32075599", "name": "P. White"}, {"authorId": + "92643932", "name": "M. Brault"}, {"authorId": "15250512", "name": "L. Tao"}, + {"authorId": "11578215", "name": "Patrick DeRoy"}, {"authorId": "13409612", + "name": "Christian Clavette"}, {"authorId": "1381646273", "name": "Shraddha + Nayak"}, {"authorId": "5924419", "name": "Leah J. Damon"}, {"authorId": "1739105914", + "name": "I. H. Kaltheuner"}, {"authorId": "4215426", "name": "Heeyoun Bunch"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1882871", "name": + "M. Geyer"}, {"authorId": "33181582", "name": "J. Iwasa"}, {"authorId": "31600919", + "name": "R. Dowell"}, {"authorId": "39787128", "name": "D. Bentley"}, {"authorId": + "48892914", "name": "W. Old"}, {"authorId": "34762957", "name": "D. Taatjes"}]}, + {"paperId": "8912d86e4aaec13eef3fbaf0af7b2ae2b8882298", "externalIds": {"MAG": + "3023156490", "DOI": "10.1074/jbc.RA119.012425", "CorpusId": 217546560, "PubMed": + "32350110"}, "corpusId": 217546560, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/8912d86e4aaec13eef3fbaf0af7b2ae2b8882298", + "title": "Phosphorylation-dependent substrate selectivity of protein kinase + B (AKT1)", "abstract": "Protein kinase B (AKT1) is a central node in a signaling + pathway that regulates cell survival. The diverse pathways regulated by AKT1 + are communicated in the cell via the phosphorylation of perhaps more than + 100 cellular substrates. AKT1 is itself activated by phosphorylation at Thr-308 + and Ser-473. Despite the fact that these phosphorylation sites are biomarkers + for cancers and tumor biology, their individual roles in shaping AKT1 substrate + selectivity are unknown. We recently developed a method to produce AKT1 with + programmed phosphorylation at either or both of its key regulatory sites. + Here, we used both defined and randomized peptide libraries to map the substrate + selectivity of site-specific, singly and doubly phosphorylated AKT1 variants. + To globally quantitate AKT1 substrate preferences, we synthesized three AKT1 + substrate peptide libraries: one based on 84 \u201cknown\u201d substrates + and two independent and larger oriented peptide array libraries (OPALs) of + \u223c1011 peptides each. We found that each phospho-form of AKT1 has common + and distinct substrate requirements. Compared with pAKT1T308, the addition + of Ser-473 phosphorylation increased AKT1 activities on some, but not all + of its substrates. This is the first report that Ser-473 phosphorylation can + positively or negatively regulate kinase activity in a substrate-dependent + fashion. Bioinformatics analysis indicated that the OPAL-activity data effectively + discriminate known AKT1 substrates from closely related kinase substrates. + Our results also enabled predictions of novel AKT1 substrates that suggest + new and expanded roles for AKT1 signaling in regulating cellular processes.", + "venue": "Journal of Biological Chemistry", "year": 2020, "referenceCount": + 63, "citationCount": 24, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925817494026/pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2020-04-29", "journal": {"volume": + "295", "pages": "8120 - 8134", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "51073035", "name": "Nileeka Balasuriya"}, {"authorId": + "2084912", "name": "N. Davey"}, {"authorId": "145916288", "name": "Jared L. + Johnson"}, {"authorId": "46935668", "name": "Huadong Liu"}, {"authorId": "1772313", + "name": "K. Biggar"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1854738", "name": "S. Li"}, {"authorId": "1398307288", "name": "P. O''Donoghue"}]}, + {"paperId": "abd557840e492110cdff0885d3c40e5c4d27945a", "externalIds": {"MAG": + "3035766511", "DOI": "10.1158/2159-8290.CD-19-1228", "CorpusId": 219988633, + "PubMed": "32571778"}, "corpusId": 219988633, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/abd557840e492110cdff0885d3c40e5c4d27945a", + "title": "Limited Environmental Serine and Glycine Confer Brain Metastasis + Sensitivity to PHGDH Inhibition.", "abstract": "A hallmark of metastasis is + the adaptation of tumor cells to new environments. Metabolic constraints imposed + by the serine and glycine-limited brain environment restrict metastatic tumor + growth. How brain metastases overcome these growth-prohibitive conditions + is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase + (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine + synthesis, is a major determinant of brain metastasis in multiple human cancer + types and preclinical models. Enhanced serine synthesis proved important for + nucleotide production and cell proliferation in highly aggressive brain metastatic + cells. In vivo, genetic suppression and pharmacological inhibition of PHGDH + attenuated brain metastasis, but not extracranial tumor growth, and improved + overall survival in mice. These results reveal that extracellular amino acid + availability determines serine synthesis pathway dependence, and suggests + that PHGDH inhibitors may be useful in the treatment of brain metastasis.", + "venue": "Cancer Discovery", "year": 2020, "referenceCount": 94, "citationCount": + 81, "influentialCitationCount": 2, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2020-06-22", "journal": {"name": "Cancer discovery"}, "authors": [{"authorId": + "5891999", "name": "B. Ngo"}, {"authorId": "115819822", "name": "Eugenie Kim"}, + {"authorId": "1600811114", "name": "Victoria Osorio-Vasquez"}, {"authorId": + "50535810", "name": "Sophia Doll"}, {"authorId": "1600820777", "name": "Sophia + Bustraan"}, {"authorId": "46875693", "name": "R. Liang"}, {"authorId": "114311983", + "name": "Alba Luengo"}, {"authorId": "34711277", "name": "Shawn M. Davidson"}, + {"authorId": "2157679423", "name": "A. Ali"}, {"authorId": "35545769", "name": + "G. Ferraro"}, {"authorId": "26984663", "name": "Grant M Fischer"}, {"authorId": + "6108327", "name": "Roozbeh Eskandari"}, {"authorId": "8118329", "name": "Diane + Kang"}, {"authorId": "1776165", "name": "Jing Ni"}, {"authorId": "1600820946", + "name": "Ariana Plasger"}, {"authorId": "5734623", "name": "Vinagolu K. Rajasekhar"}, + {"authorId": "4306515", "name": "Edward R. Kastenhuber"}, {"authorId": "145170581", + "name": "Sarah Bacha"}, {"authorId": "49408849", "name": "Roshan K. Sriram"}, + {"authorId": "40353456", "name": "Benjamin D. Stein"}, {"authorId": "3543494", + "name": "S. Bakhoum"}, {"authorId": "3579975", "name": "M. Snuderl"}, {"authorId": + "10371243", "name": "P. Cotzia"}, {"authorId": "1846047", "name": "J. Healey"}, + {"authorId": "10006170", "name": "N. Mainolfi"}, {"authorId": "2272920", "name": + "Vipin Suri"}, {"authorId": "2054407866", "name": "Adam J. Friedman"}, {"authorId": + "47769189", "name": "M. Manfredi"}, {"authorId": "1843680", "name": "D. Sabatini"}, + {"authorId": "151477189", "name": "Drew R. Jones"}, {"authorId": "145684949", + "name": "Min Yu"}, {"authorId": "50985038", "name": "Jean J. Zhao"}, {"authorId": + "32514332", "name": "R. Jain"}, {"authorId": "5460116", "name": "K. Keshari"}, + {"authorId": "2172770398", "name": "M. Davies"}, {"authorId": "3804233", "name": + "M. V. Vander Heiden"}, {"authorId": "4586359", "name": "E. Hernando"}, {"authorId": + "144979479", "name": "M. Mann"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5141475", "name": "M. Pacold"}]}, {"paperId": "b047faadd4ccc0e48f819dcea00523bd9e3c22dd", + "externalIds": {"MAG": "2985842281", "DOI": "10.1021/acsmedchemlett.9b00402", + "CorpusId": 209581796, "PubMed": "32184968"}, "corpusId": 209581796, "publicationVenue": + {"id": "513ddb82-8e57-474b-852a-bae692e8ebfa", "name": "ACS Medicinal Chemistry + Letters", "type": "journal", "alternate_names": ["AC Med Chem Lett"], "issn": + "1948-5875", "url": "https://pubs.acs.org/journal/amclct", "alternate_urls": + ["https://pubs.acs.org/loi/amclct", "http://pubs.acs.org/journal/amclct"]}, + "url": "https://www.semanticscholar.org/paper/b047faadd4ccc0e48f819dcea00523bd9e3c22dd", + "title": "Structure-Activity Relationship Study of Covalent Pan-phosphatidylinositol + 5-Phosphate 4-Kinase Inhibitors.", "abstract": "Phosphatidylinositol 5-phosphate + 4-kinases (PI5P4Ks) are important molecular players in a variety of diseases, + such as cancer. Currently available PI5P4K inhibitors are reversible small + molecules, which may lack selectivity and sufficient cellular on-target activity. + In this study, we present a new class of covalent pan-PI5P4K inhibitors with + potent biochemical and cellular activity. Our designs are based on THZ-P1-2, + a covalent PI5P4K inhibitor previously developed in our lab. Here, we report + further structure-guided optimization and structure-activity relationship + (SAR) study of this scaffold, resulting in compound 30, which retained biochemical + and cellular potency, while demonstrating a significantly improved selectivity + profile. Furthermore, we confirm that the inhibitors show efficient binding + affinity in the context of HEK 293T cells using isothermal CETSA methods. + Taken together, compound 30 represents a highly selective pan-PI5P4K covalent + lead molecule.", "venue": "ACS Medicinal Chemistry Letters", "year": 2020, + "referenceCount": 35, "citationCount": 11, "influentialCitationCount": 0, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2020-03-12", "journal": {"volume": + "11 3", "pages": "\n 346-352\n ", "name": "ACS medicinal chemistry + letters"}, "authors": [{"authorId": "16018077", "name": "Theresa D. Manz"}, + {"authorId": "6443517", "name": "S. Sivakumaren"}, {"authorId": "6707118", + "name": "Adam Yasgar"}, {"authorId": "143999402", "name": "M. Hall"}, {"authorId": + "29195749", "name": "Mindy I. Davis"}, {"authorId": "91486080", "name": "H. + Seo"}, {"authorId": "5223652", "name": "Joseph D. Card"}, {"authorId": "2297254", + "name": "S. Ficarro"}, {"authorId": "13574443", "name": "Hyeseok Shim"}, {"authorId": + "2605597", "name": "J. Marto"}, {"authorId": "1400570681", "name": "S. Dhe-Paganon"}, + {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "3275486", "name": + "M. Boxer"}, {"authorId": "145183304", "name": "A. Simeonov"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "145829790", "name": "M. Shen"}, + {"authorId": "2262535", "name": "Tinghu Zhang"}, {"authorId": "11404167", + "name": "F. M. Ferguson"}, {"authorId": "3977406", "name": "N. Gray"}]}, {"paperId": + "b079b2292a25c9f6e73634ccd1746f2187694e00", "externalIds": {"PubMedCentral": + "7021536", "MAG": "3004455455", "DOI": "10.1016/j.gore.2020.100546", "CorpusId": + 211213044, "PubMed": "32083163"}, "corpusId": 211213044, "publicationVenue": + {"id": "753bdea8-6488-43c7-89cf-6a9f5897123c", "name": "Gynecologic Oncology + Reports", "type": "journal", "alternate_names": ["Gynecologic oncology reports", + "Gynecol oncol rep", "Gynecol Oncol Rep"], "issn": "2352-5789", "url": "https://www.journals.elsevier.com/gynecologic-oncology-reports/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/23525789"]}, + "url": "https://www.semanticscholar.org/paper/b079b2292a25c9f6e73634ccd1746f2187694e00", + "title": "Results of an abbreviated phase II study of AKT inhibitor MK-2206 + in the treatment of recurrent platinum-resistant high grade serous ovarian, + fallopian tube, or primary peritoneal carcinoma (NCT 01283035)", "abstract": + null, "venue": "Gynecologic Oncology Reports", "year": 2020, "referenceCount": + 17, "citationCount": 8, "influentialCitationCount": 1, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["CaseReport"], "publicationDate": "2020-02-03", "journal": + {"volume": "32", "name": "Gynecologic Oncology Reports"}, "authors": [{"authorId": + "50288013", "name": "Elizabeth K. Lee"}, {"authorId": "1418847559", "name": + "Z. Tan-Wasielewski"}, {"authorId": "6128162", "name": "C. Aghajanian"}, {"authorId": + "3124983", "name": "R. Coleman"}, {"authorId": "49142258", "name": "J. Curtis"}, + {"authorId": "2319517", "name": "M. Hirsch"}, {"authorId": "6927295", "name": + "U. Matulonis"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "39667616", "name": "L. Doyle"}, + {"authorId": "2108419806", "name": "Joyce F. Liu"}]}, {"paperId": "b6d957b5c6136940be6ca4a261c0bb0bdee47514", + "externalIds": {"MAG": "3007653203", "PubMedCentral": "7056863", "DOI": "10.3389/fchem.2020.00147", + "CorpusId": 211518735, "PubMed": "32175313"}, "corpusId": 211518735, "publicationVenue": + {"id": "7f0649e7-1c25-49d4-a210-6177946c6d4a", "name": "Frontiers in Chemistry", + "type": "journal", "alternate_names": ["Front Chem"], "issn": "2296-2646", + "url": "http://www.frontiersin.org/Chemistry", "alternate_urls": ["http://www.frontiersin.org/Chemistry/archive", + "http://journal.frontiersin.org/journal/chemistry", "https://www.frontiersin.org/journals/chemistry"]}, + "url": "https://www.semanticscholar.org/paper/b6d957b5c6136940be6ca4a261c0bb0bdee47514", + "title": "Development of a CDK10/CycM in vitro Kinase Screening Assay and + Identification of First Small-Molecule Inhibitors", "abstract": "Cyclin-dependent + kinases (CDKs) constitute a family of 20 serine/threonine protein kinases + that play pivotal roles in the regulation of numerous important molecular + and cellular processes. CDKs have long been considered promising therapeutic + targets in a variety of pathologies, and the recent therapeutic success of + CDK4/6 inhibitors in breast cancers has renewed interest in their therapeutic + potential. Small-molecule inhibitors have been identified for every human + CDK, except for CDK10. The only recent discovery of an activating cyclin (CycM) + for CDK10 enabled us to identify its first phosphorylation substrates and + gain insights into its biological functions. Yet, our knowledge of this kinase + remains incomplete, despite it being the only member of its family that causes + severe human developmental syndromes, when mutated either on the cyclin or + the CDK moiety. CDK10 small-molecule inhibitors would be useful in exploring + the functions of this kinase and gauging its potential as a therapeutic target + for some cancers. Here, we report the identification of an optimized peptide + phosphorylation substrate of CDK10/CycM and the development of the first homogeneous, + miniaturized CDK10/CycM in vitro kinase assay. We reveal the ability of known + CDK inhibitors, among which clinically tested SNS-032, riviciclib, flavopiridol, + dinaciclib, AZD4573 and AT7519, to potently inhibit CDK10/CycM. We also show + that NVP-2, a strong, remarkably selective CDK9 inhibitor is an equally potent + CDK10/CycM inhibitor. Finally, we validate this kinase assay for applications + in high-throughput screening campaigns to discover new, original CDK10 inhibitors.", + "venue": "Frontiers in Chemistry", "year": 2020, "referenceCount": 46, "citationCount": + 9, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.frontiersin.org/articles/10.3389/fchem.2020.00147/pdf", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2020-02-27", "journal": {"volume": "8", "name": "Frontiers in Chemistry"}, + "authors": [{"authorId": "144017436", "name": "Thomas Robert"}, {"authorId": + "145916288", "name": "Jared L. Johnson"}, {"authorId": "1508394280", "name": + "Roxane Guichaoua"}, {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": + "39747539", "name": "S. Bach"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "8339673", "name": "P. Colas"}]}, {"paperId": "b704acbdf74290834c727ecd80dd2c86e1227c86", + "externalIds": {"MAG": "3083160159", "DOI": "10.1158/1538-7445.am2020-ng16", + "CorpusId": 225366119}, "corpusId": 225366119, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/b704acbdf74290834c727ecd80dd2c86e1227c86", + "title": "Abstract NG16: DoublePIK3CAmutations incisincrease oncogenicity + and sensitivity to PI3K\u03b1 inhibitors", "abstract": "PIK3CA is the most + frequently mutated oncogene across all human cancers, and codes for p110\u03b1, + the catalytic subunit of the PI3K complex. PI3K catalyzes the phosphorylation + of the lipid PIP2 to PIP3, which initiates a downstream signaling cascade + involving the activation of AKT and mTOR. Hotspot E545K and H1047R mutations + constitutively activate PI3K and are oncogenic in multiple cancer histologies + including breast cancer, where PIK3CA mutations are present in 40% of tumors + and are a target for cancer therapy. Recently, the PI3K\u03b1 inhibitor alpelisib + has demonstrated improved PFS in patients with ER+ PIK3CA mutant metastatic + breast cancer on a phase 3 randomized clinical trial, resulting in its FDA + approval. In early clinical trials, we observed a population of patients with + displayed prolonged clinical benefit to alpelisib, with double PIK3CA mutant + tumors. This prompted us to undertake a comprehensive analysis of the prevalence + of multiple PIK3CA mutations and to investigate their potential biological + relevance and correlation with sensitivity to PI3K\u03b1 inhibitors.We analyzed + multiple independent primary and metastatic tumor cohorts and found that 10-15% + of all PIK3CA mutant tumors across all cancer histologies contain multiple + PIK3CA mutations, the vast majority of which carry exactly two mutations. + Double mutations occur at specific amino acid positions by codon enrichment + analysis, where the most frequent combinations in breast cancer are comprised + of a canonical \u201cmajor mutant\u201d hotspot (involving either E542, E545, + or H1047) combined with a second \u201cminor mutant\u201d site (involving + either E453, E726, or M1043). Double PIK3CA mutations are enriched in ER+/HER2- + breast cancers and occur at similar frequencies in therapy-naive primary tumors + and metastatic tumors. To study the allelic configuration of double mutations, + we leveraged single molecule real time sequencing (SMRT-seq) on fresh breast + tumor samples from patients known to carry two PIK3CA mutations in their tumors + by NGS. Six tumors representative of the most frequent double mutants in breast + cancer were obtained from patients, and were analyzed by SMRT-seq. All contained + double mutations in cis. We overexpressed double cis mutants and constituent + single mutants in nontransformed and ER+ breast cancer cells. Double PIK3CA + mutations in cis increased downstream PI3K pathway signaling and cell/tumor + proliferation in vitro and in vivo, when compared to single mutations. In + contrast, mutations in trans do not increase cell signaling or growth proliferation + more than single mutations.The prevailing model of PI3K activation occurs + through the engagement of the p85\u03b1 regulatory subunit with phosphotyrosines + on RTK signaling complexes, which relieves catalytic inhibition. Single oncogenic + mutations recapitulate these events by weakening the interactions between + p110\u03b1 and p85\u03b1 (\u201cdisrupters\u201d), or by promoting binding + to membrane (\u201cbinders\u201d). We purified recombinant full length PI3K\u03b1 + complexes containing single and double cis p110\u03b1 mutations to dissect + the biochemical mechanisms by which these double PIK3CA mutations in cis modulate + kinase activity. We demonstrate that cis mutants have increased kinase activity + compared to single mutants and that this activation is due to both increased + p85\u03b1 disruption and increased lipid binding, compared to single mutants.We + tested whether cis mutant cells exhibit differential sensitivity to PI3K\u03b1 + inhibitors. While in the absence of treatment, cis mutant signaling is increased + compared to single mutants, treatment with the PI3K\u03b1 inhibitors alpelisib + or GDC-0077 results in a similar PI3K pathway inhibition in nontransformed + and ER+ breast cancer cells. With respect to cell viability, E545K and H1047R + major hotspot mutants are more sensitive to alpelisib and GDC-0077 compared + to minor mutants and WT. In turn, all cis mutants are synergistically more + sensitive to alpelisib and GDC-0077 compared to single major and minor hotspots.We + analyzed response data from SANDPIPER, a randomized phase 3 clinical trial + that tested the efficacy of the ER degrader fulvestrant with or without the + PI3K\u03b1/\u03b3/\u03b4 inhibitor taselisib in metastatic ER+ PIK3CA mutant + breast cancer. We used ctDNA to detect the presence of PIK3CA mutations. PIK3CA + mutant patients on the taselisib arm had an objective response rate (ORR) + of 20.3% vs 9.7% compared to the placebo arm, which was statistically significant, + confirming that PIK3CA mutation predicts response to PI3K\u03b1 inhibition. + We then compared responses of patients with single vs multiple mutations. + Single mutant patients on the taselisib arm had an ORR of 18.1% vs 10.0% compared + to the placebo arm, which was not statistically significant. On the contrary, + multiple mutant patients on the taselisib arm achieved an ORR of 30.2% vs + 8.7% compared to the placebo arm, which was statistically significant. These + findings confirm that breast cancer patients with multiple mutant tumors achieve + higher clinical benefit to PI3K\u03b1 inhibition compared to single mutant + tumors.In this work, we have identified double mutations in cis as a novel, + and relatively frequent, genomic alteration in PIK3CA, which translates into + a clinically meaningful number of patients who may derive additional benefit + from targeted therapy. Our results implicate a model of oncogene addiction + to double mutant PIK3CA in breast cancer, with graded levels of activation + and inhibition for single vs double mutants. PI3K\u03b1 inhibitors are now + a standard of care in PIK3CA mutant ER+ metastatic breast cancer and are being + explored in other PIK3CA mutant tumor histologies. Our findings provide a + rationale for testing whether patients with multiple PIK3CA mutant tumors + are exquisitely sensitive to PI3K\u03b1 inhibitors. Citation Format: Neil + Vasan, Pedram Razavi, Jared L. Johnson, Hong Shao, Hardik Shah, Alesia Antoine, + Erik Ladewig, Alexander Gorelick, Ting-Yu Lin, Eneda Toska, Guotai Xu, Abiha + Kazmi, Matthew T. Chang, Barry S. Taylor, Maura N. Dickler, Komal Jhaveri, + Sarat Chandarlapaty, Raul Rabadan, Ed Reznik, Melissa L. Smith, Robert Sebra, + Frauke Schimmoller, Timothy R. Wilson, Lori S. Friedman, Lewis C. Cantley, + Maurizio Scaltriti, Jose Baselga. Double PIK3CA mutations in cis increase + oncogenicity and sensitivity to PI3K\u03b1 inhibitors [abstract]. In: Proceedings + of the Annual Meeting of the American Association for Cancer Research 2020; + 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 + Suppl):Abstract nr NG16.", "venue": "", "year": 2020, "referenceCount": 0, + "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2020-08-15", "journal": {"volume": + "80", "name": "Cancer Research"}, "authors": [{"authorId": "35123724", "name": + "N. Vasan"}, {"authorId": "3224289", "name": "P. Razavi"}, {"authorId": "145916288", + "name": "Jared L. Johnson"}, {"authorId": "2959236", "name": "H. Shao"}, {"authorId": + "49820132", "name": "H. Shah"}, {"authorId": "49335811", "name": "Alesia Antoine"}, + {"authorId": "3139198", "name": "Erik Ladewig"}, {"authorId": "48892954", + "name": "A. Gorelick"}, {"authorId": "144181325", "name": "Ting-Yu Lin"}, + {"authorId": "4733908", "name": "E. Toska"}, {"authorId": "51290929", "name": + "Guotai Xu"}, {"authorId": "150907238", "name": "Abiha Kazmi"}, {"authorId": + "2141904248", "name": "Matthew T. Chang"}, {"authorId": "36898514", "name": + "B. Taylor"}, {"authorId": "4713308", "name": "M. Dickler"}, {"authorId": + "47352468", "name": "K. Jhaveri"}, {"authorId": "6037809", "name": "S. Chandarlapaty"}, + {"authorId": "40620158", "name": "R. Rabad\u00e1n"}, {"authorId": "145632788", + "name": "E. Reznik"}, {"authorId": "2116670076", "name": "M. Smith"}, {"authorId": + "46517710", "name": "R. Sebra"}, {"authorId": "5323777", "name": "F. Schimmoller"}, + {"authorId": "2017652", "name": "T. Wilson"}, {"authorId": "48530297", "name": + "L. Friedman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "8336319", "name": "M. Scaltriti"}, {"authorId": "144806171", "name": "J. + Baselga"}]}, {"paperId": "bfbd98ef8086d158453befcad0667e00ccd437f8", "externalIds": + {"PubMedCentral": "7785256", "DOI": "10.1038/s41586-020-2630-0", "CorpusId": + 231960831}, "corpusId": 231960831, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/bfbd98ef8086d158453befcad0667e00ccd437f8", + "title": "Age-induced methylmalonic acid accumulation promotes tumor progression", + "abstract": null, "venue": "Nature", "year": 2020, "referenceCount": 0, "citationCount": + 24, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://lirias.kuleuven.be/bitstream/123456789/661819/2/2020.06.04.135087v1.full.pdf", + "status": null}, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2020-07-14", + "journal": {"volume": "585", "pages": "283 - 287", "name": "Nature"}, "authors": + [{"authorId": "2087116099", "name": "Ana P Gomes"}, {"authorId": "3324022", + "name": "Didem Ilter"}, {"authorId": "121128193", "name": "V. Low"}, {"authorId": + "83689245", "name": "J. Endress"}, {"authorId": "52621189", "name": "J. Fern\u00e1ndez-Garc\u00eda"}, + {"authorId": "1887417083", "name": "A. Rosenzweig"}, {"authorId": "50356549", + "name": "Tanya Schild"}, {"authorId": "11236293", "name": "D. Broekaert"}, + {"authorId": "1887422976", "name": "Adnan Ahmed"}, {"authorId": "8444258", + "name": "M. Planque"}, {"authorId": "2382021", "name": "Ilaria Elia"}, {"authorId": + "1886508939", "name": "Julie Han"}, {"authorId": "1887752916", "name": "Charles + G. Kinzig"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": + "5135907", "name": "A. Mutvei"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "144285023", "name": "R. de Cabo"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4622316", "name": "Noah Dephoure"}, {"authorId": + "46775302", "name": "S. Fendt"}, {"authorId": "4037343", "name": "J. Blenis"}]}, + {"paperId": "c04af48f79107d1167907e6b60205310f868f6b8", "externalIds": {"MAG": + "3034026561", "DOI": "10.1158/2159-8290.CD-19-1262", "CorpusId": 219552322, + "PubMed": "32513774"}, "corpusId": 219552322, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/c04af48f79107d1167907e6b60205310f868f6b8", + "title": "The INPP4B Tumor Suppressor Modulates EGFR Trafficking and Promotes + Triple Negative Breast Cancer.", "abstract": "Inactivation of the tumor suppressor + lipid phosphatase INPP4B is common in triple negative breast cancer (TNBC). + We generated a genetically-engineered TNBC mouse model deficient in INPP4B. + We found a dose-dependent increase in tumor incidence in INPP4B homozygous + and heterozygous knockout mice compared to wild-type, supporting a role for + INPP4B as a tumor suppressor in TNBC. Tumors derived from INPP4B knockout + mice are enriched for AKT and MEK gene signatures. Consequently, mice with + INPP4B deficiency are more sensitive to PI3K or MEK inhibitors, compared to + wild-type mice. Mechanistically, we found that INPP4B deficiency increases + PI(3,4)P2 levels in endocytic vesicles but not at the plasma membrane. Moreover, + INPP4B loss delays degradation of EGFR and MET, while promoting recycling + of RTKs, thus enhancing the duration and amplitude of signaling output upon + growth factor stimulation. Therefore, INPP4B inactivation in TNBC promotes + tumorigenesis by modulating RTK recycling and signaling duration.", "venue": + "Cancer Discovery", "year": 2020, "referenceCount": 96, "citationCount": 22, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://aacrjournals.org/cancerdiscovery/article-pdf/10/8/1226/1814650/1226.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2020-06-08", "journal": + {"name": "Cancer discovery"}, "authors": [{"authorId": "2146671919", "name": + "Hui Liu"}, {"authorId": "4422893", "name": "M. Paddock"}, {"authorId": "2113220569", + "name": "Haibin Wang"}, {"authorId": "47107919", "name": "Charles J Murphy"}, + {"authorId": "13850298", "name": "Renee C. Geck"}, {"authorId": "40810332", + "name": "A. Navarro"}, {"authorId": "31554501", "name": "G. Wulf"}, {"authorId": + "150097652", "name": "O. Elemento"}, {"authorId": "3838808", "name": "V. Haucke"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145751285", "name": + "A. Toker"}]}, {"paperId": "d0a142a766ddb29f861369a80dacf1f778cbe2e0", "externalIds": + {"MAG": "3010345862", "DOI": "10.1101/2020.03.03.974980", "CorpusId": 214723130}, + "corpusId": 214723130, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/d0a142a766ddb29f861369a80dacf1f778cbe2e0", + "title": "Limited Environmental Serine Confers Sensitivity to PHGDH Inhibition + in Brain Metastasis", "abstract": "A hallmark of metastasis is the adaptation + of tumor cells to new environments. Although it is well established that the + metabolic milieu of the brain is severely deprived of nutrients, particularly + the amino acids serine and its catabolite glycine, how brain metastases rewire + their metabolism to survive in the nutrient-limited environment of the brain + is poorly understood. Here we demonstrate that cell-intrinsic de novo serine + synthesis is a major determinant of brain metastasis. Whole proteome comparison + of triple-negative breast cancer (TNBC) cells that differ in their capacity + to colonize the brain reveals that 3-phosphoglycerate dehydrogenase (PHGDH), + which catalyzes the rate-limiting step of glucose-derived serine synthesis, + is the most significantly upregulated protein in cells that efficiently metastasize + to the brain. Genetic silencing or pharmacological inhibition of PHGDH attenuated + brain metastasis and improved overall survival in mice, whereas expression + of catalytically active PHGDH in a non-brain trophic cell line promoted brain + metastasis. Collectively, these findings indicate that nutrient availability + determines serine synthesis pathway dependence in brain metastasis, and suggest + that PHGDH inhibitors may be useful in the treatment of patients with cancers + that have spread to the brain. Statement of Significance Our study highlights + how limited serine and glycine availability within the brain microenvironment + potentiates tumor cell sensitivity to serine synthesis inhibition. This finding + underscores the importance of studying cancer metabolism in physiologically-relevant + contexts, and provides a rationale for using PHGDH inhibitors to treat brain + metastasis.", "venue": "bioRxiv", "year": 2020, "referenceCount": 72, "citationCount": + 2, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.biorxiv.org/content/biorxiv/early/2020/03/04/2020.03.03.974980.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2020-03-04", "journal": {"name": "bioRxiv"}, "authors": + [{"authorId": "5891999", "name": "B. Ngo"}, {"authorId": "115819822", "name": + "Eugenie Kim"}, {"authorId": "1600811114", "name": "Victoria Osorio-Vasquez"}, + {"authorId": "50535810", "name": "Sophia Doll"}, {"authorId": "1600820777", + "name": "Sophia Bustraan"}, {"authorId": "114311983", "name": "Alba Luengo"}, + {"authorId": "34711277", "name": "Shawn M. Davidson"}, {"authorId": "2157679423", + "name": "A. Ali"}, {"authorId": "4469681", "name": "G. Ferraro"}, {"authorId": + "8118329", "name": "Diane Kang"}, {"authorId": "1776165", "name": "Jing Ni"}, + {"authorId": "46875693", "name": "R. Liang"}, {"authorId": "1600820946", "name": + "Ariana Plasger"}, {"authorId": "4306515", "name": "Edward R. Kastenhuber"}, + {"authorId": "6108327", "name": "Roozbeh Eskandari"}, {"authorId": "145170581", + "name": "Sarah Bacha"}, {"authorId": "1600821371", "name": "Roshan K. Siriam"}, + {"authorId": "3543494", "name": "S. Bakhoum"}, {"authorId": "6424987", "name": + "Edouard Mullarky"}, {"authorId": "3579975", "name": "M. Snuderl"}, {"authorId": + "10371243", "name": "P. Cotzia"}, {"authorId": "10006170", "name": "N. Mainolfi"}, + {"authorId": "2272920", "name": "Vipin Suri"}, {"authorId": "2054407866", + "name": "Adam J. Friedman"}, {"authorId": "47769189", "name": "M. Manfredi"}, + {"authorId": "1843680", "name": "D. Sabatini"}, {"authorId": "151477189", + "name": "Drew R. Jones"}, {"authorId": "145684949", "name": "Min Yu"}, {"authorId": + "50985038", "name": "Jean J. Zhao"}, {"authorId": "32514332", "name": "R. + Jain"}, {"authorId": "3804233", "name": "M. V. Vander Heiden"}, {"authorId": + "4586359", "name": "E. Hernando"}, {"authorId": "144979479", "name": "M. Mann"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5141475", "name": + "M. Pacold"}]}, {"paperId": "d4c0f402152727c1273dc8fe0f3b54faa932a711", "externalIds": + {"MAG": "3071340143", "DOI": "10.1038/s41586-020-2630-0", "CorpusId": 221179251, + "PubMed": "32814897"}, "corpusId": 221179251, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/d4c0f402152727c1273dc8fe0f3b54faa932a711", + "title": "Age-induced accumulation of methylmalonic acid promotes tumour progression", + "abstract": null, "venue": "Nature", "year": 2020, "referenceCount": 55, "citationCount": + 41, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://lirias.kuleuven.be/bitstream/123456789/661819/2/2020.06.04.135087v1.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2020-08-19", "journal": + {"volume": "", "pages": "1-5", "name": "Nature"}, "authors": [{"authorId": + "2087116099", "name": "Ana P Gomes"}, {"authorId": "3324022", "name": "Didem + Ilter"}, {"authorId": "121128193", "name": "V. Low"}, {"authorId": "83689245", + "name": "J. Endress"}, {"authorId": "52621189", "name": "J. Fern\u00e1ndez-Garc\u00eda"}, + {"authorId": "1887417083", "name": "A. Rosenzweig"}, {"authorId": "50356549", + "name": "Tanya Schild"}, {"authorId": "11236293", "name": "D. Broekaert"}, + {"authorId": "1887422976", "name": "Adnan Ahmed"}, {"authorId": "8444258", + "name": "M. Planque"}, {"authorId": "2382021", "name": "Ilaria Elia"}, {"authorId": + "1886508939", "name": "Julie Han"}, {"authorId": "1887752916", "name": "Charles + G. Kinzig"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": + "5135907", "name": "A. Mutvei"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "144285023", "name": "R. de Cabo"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4622316", "name": "Noah Dephoure"}, {"authorId": + "46775302", "name": "S. Fendt"}, {"authorId": "4037343", "name": "J. Blenis"}]}, + {"paperId": "d6d13b639d29baf68684cbf7356a59d04c53deef", "externalIds": {"DOI": + "10.1186/s13058-020-01354-y", "CorpusId": 255980355}, "corpusId": 255980355, + "publicationVenue": {"id": "1290af6c-c79c-4253-8957-8db4a6069766", "name": + "Breast Cancer Research", "type": "journal", "alternate_names": ["Breast Cancer + Res"], "issn": "1465-5411", "url": "http://breast-cancer-research.com/"}, + "url": "https://www.semanticscholar.org/paper/d6d13b639d29baf68684cbf7356a59d04c53deef", + "title": "Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, + in patients with metastatic triple-negative breast cancer", "abstract": null, + "venue": "Breast Cancer Research", "year": 2020, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2020-11-02", + "journal": {"volume": "22", "name": "Breast Cancer Research"}, "authors": + [{"authorId": "1401041241", "name": "A. Garrido-Castro"}, {"authorId": "143772689", + "name": "C. Saura"}, {"authorId": "1393643694", "name": "R. Barroso-Sousa"}, + {"authorId": "143887802", "name": "Hao Guo"}, {"authorId": "4316212", "name": + "E. Ciruelos"}, {"authorId": "144441047", "name": "B. Bermejo"}, {"authorId": + "1901703", "name": "J. Gavil\u00e1"}, {"authorId": "49229190", "name": "V. + Serra"}, {"authorId": "145594197", "name": "A. Prat"}, {"authorId": "3372070", + "name": "L. Par\u00e9"}, {"authorId": "145716996", "name": "P. C\u00e9liz"}, + {"authorId": "152815847", "name": "P. Villagrasa"}, {"authorId": "2111151410", + "name": "Yisheng Li"}, {"authorId": "37392807", "name": "J. Savoie"}, {"authorId": + "2155024736", "name": "Zhan-ping Xu"}, {"authorId": "48121794", "name": "Carlos + L Arteaga"}, {"authorId": "2101923", "name": "I. Krop"}, {"authorId": "2344124", + "name": "D. Solit"}, {"authorId": "2084778769", "name": "G. Mills"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2165631687", "name": "Eric + P Winer"}, {"authorId": "35141217", "name": "N. Lin"}, {"authorId": "143607446", + "name": "J. Rod\u00f3n"}]}, {"paperId": "d8422cb2ed7c2612f66b0691fde34717a02c9d7b", + "externalIds": {"MAG": "3043008369", "DOI": "10.1038/s42255-020-0225-6", "CorpusId": + 220699548, "PubMed": "32694797"}, "corpusId": 220699548, "publicationVenue": + {"id": "f8dd1b61-789d-48ec-b550-a6245826a9aa", "name": "Nature Metabolism", + "alternate_names": ["Nat Metab"], "issn": "2522-5812", "url": "https://www.nature.com/natmetab/"}, + "url": "https://www.semanticscholar.org/paper/d8422cb2ed7c2612f66b0691fde34717a02c9d7b", + "title": "A ''fast''er way to treat breast cancer.", "abstract": null, "venue": + "Nature Metabolism", "year": 2020, "referenceCount": 12, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2020-07-01", "journal": {"volume": "2 7", "pages": "\n 559-560\n ", + "name": "Nature metabolism"}, "authors": [{"authorId": "145524334", "name": + "M. Goncalves"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "dcc3c19495bc55b355780ff79017973d9fccc468", "externalIds": {"MAG": "3092576713", + "DOI": "10.1158/1557-3125.PI3K-MTOR18-A21", "CorpusId": 225150070}, "corpusId": + 225150070, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/dcc3c19495bc55b355780ff79017973d9fccc468", + "title": "Abstract A21: Compound PIK3CA mutations support a mutational dose-response + model for oncogene activation and response to PI3K inhibitor targeted therapy + in breast cancer", "abstract": "PIK3CA mutations represent the most frequent + oncogenic driver lesion found across all human cancers. Given that single + PIK3CA mutations are a predictive biomarker for response to PI3K inhibition, + and that these clinical benefits are small, we hypothesized that additional + genomic factors may cooperate with single PIK3CA mutations in oncogenesis + and response to PI3K inhibitors. We analyzed several large pan-cancer datasets + and have discovered a phenomenon of dual PIK3CA mutations in 15% of all PIK3CA-mutant + cancers, including breast cancer. Dual PIK3CA mutations are clonal, are found + in both primary untreated and metastatic tumors, and are enriched at conserved + amino acid positions. We have proved that the majority of dual PIK3CA mutations\u2014including + the most frequent dual PIK3CA mutant combinations in breast cancer\u2014are + in cis compound mutations (i.e., on the same allele, resulting in a protein + molecule with two mutations) in patient samples and cell lines, as shown through + multiple sequencing techniques including long-range single-molecule real-time + sequencing (SMRT-seq). Compound PIK3CA mutations increase PI3K pathway signaling + and growth proliferation in nontransformed cells and cancer cells in vitro + and in vivo. Biochemical experiments using recombinant PI3K complexes reveal + a mechanism where compound mutants increase PI3K complex thermal instability, + resulting in increased kinase activity and liposome binding as compared to + single mutants. Compound PIK3CA mutations render cells more sensitive to the + PI3K\u03b1 inhibitors BYL719 and GDC-0077 than single PIK3CA mutations. These + data translate to the clinic, where patients with dual PIK3CA-mutant metastatic + breast cancer exhibit more durable responses to PI3K inhibition versus patients + with single PIK3CA-mutant breast tumors. Our data support a novel mutational + dose-response model for oncogene activation, where compound mutations amplify + PI3K signaling and growth to a greater degree than single mutants, resulting + in increased sensitivity to PI3K\u03b1 inhibitor targeted therapy. These findings + also have therapeutic relevance, where compound PIK3CA mutations may be a + superior predictive biomarker for response to PI3K\u03b1 inhibitors than single + PIK3CA mutations, across PIK3CA-mutant cancers. Citation Format: Neil Vasan, + Jared Johnson, Hong Shao, Pedram Razavi, Alexander Gorelick, Erik Ladewig, + Alesia Antoine, Hardik Shah, Eneda Toska, Guotai Xu, Abiha Kazmi, Barry Taylor, + Komal Jhaveri, Maura Dickler, Elisa de Stanchina, Eduard Reznik, Raul Rabadan, + Melissa Smith, Robert Sebra, Lewis Cantley, Maurizio Scaltriti, Jose Baselga. + Compound PIK3CA mutations support a mutational dose-response model for oncogene + activation and response to PI3K inhibitor targeted therapy in breast cancer + [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR + Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer + Res 2020;18(10_Suppl):Abstract nr A21.", "venue": "", "year": 2020, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2020-10-01", "journal": {"volume": + "18", "name": "Molecular Cancer Research"}, "authors": [{"authorId": "35123724", + "name": "N. Vasan"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, + {"authorId": "2959236", "name": "H. Shao"}, {"authorId": "3224289", "name": + "P. Razavi"}, {"authorId": "48892954", "name": "A. Gorelick"}, {"authorId": + "3139198", "name": "Erik Ladewig"}, {"authorId": "49335811", "name": "Alesia + Antoine"}, {"authorId": "49820132", "name": "H. Shah"}, {"authorId": "4733908", + "name": "E. Toska"}, {"authorId": "51290929", "name": "Guotai Xu"}, {"authorId": + "150907238", "name": "Abiha Kazmi"}, {"authorId": "36898514", "name": "B. + Taylor"}, {"authorId": "47352468", "name": "K. Jhaveri"}, {"authorId": "4713308", + "name": "M. Dickler"}, {"authorId": "6567674", "name": "E. de Stanchina"}, + {"authorId": "145632788", "name": "E. Reznik"}, {"authorId": "40620158", "name": + "R. Rabad\u00e1n"}, {"authorId": "2116670076", "name": "M. Smith"}, {"authorId": + "46517710", "name": "R. Sebra"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "8336319", "name": "M. Scaltriti"}, {"authorId": "144806171", + "name": "J. Baselga"}]}, {"paperId": "e852673197a1eec76b5db1dc058115533b8e0a4e", + "externalIds": {"MAG": "3111004311", "DOI": "10.1093/neuonc/noaa215.926", + "CorpusId": 230659238}, "corpusId": 230659238, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/e852673197a1eec76b5db1dc058115533b8e0a4e", + "title": "TAMI-38. CYSTEINE-PROMOTING COMPOUNDS INDUCE MITOCHONDRIAL TOXICITY + IN GLIOBLASTOMA THROUGH ALTERED PYRUVATE AND SERINE METABOLISM", "abstract": + "\n Glioblastoma (GBM) remains a poorly treatable disease with high mortality. + Tumor metabolism in GBM is a critical mechanism responsible for accelerated + growth because of upregulation of glucose, amino acid, and fatty acid utilization. + However, little is known about the metabolic alterations that are specific + to GBM and that are targetable with FDA-approved compounds. To investigate + tumor metabolism signatures unique to GBM, we interrogated the TCGA and a + cancer metabolite database for alterations in glucose and amino acid signatures + in GBM relative to other human cancers and relative to low-grade glioma. From + these analyses, we found that GBM exhibits the highest levels of cysteine + and methionine pathway gene expression of 32 human cancers and that GBM exhibits + high levels of cysteine-related metabolites compared to low-grade gliomas. + To study the role of cysteine in GBM pathogenesis, we treated patient-derived + GBM cells with a variety of FDA-approved cyst(e)ine-promoting compounds in + vitro, including N-acetylcysteine (NAC) and the cephalosporin antibiotic, + Ceftriaxone (CTX), which induces cystine import through System Xc transporter + upregulation. Cysteine-promoting compounds, including NAC and CTX, inhibit + growth of GBM cells, which is exacerbated by glucose deprivation. This growth + inhibition is associated with reduced mitochondrial metabolism, manifest by + reduction in ATP, NADPH/NADP+ ratio, mitochondrial membrane potential, and + oxygen consumption rate. Metabolic tracing experiments with 13C6-glucose demonstrate + that L-serine is rapidly depleted in GBM cells upon treatment with NAC and + CTX, and exogenous serine rescues NAC- and CTX-mediated cell growth inhibition. + In addition, these compounds reduce GBM mitochondrial pyruvate transport. + We show that cysteine-promoting compounds reduce cell growth and induce mitochondrial + toxicity in GBM, which may be due to rapid serine depletion and reduced mitochondrial + pyruvate transport. This metabolic phenotype is exacerbated by glucose deprivation. + This pathway is targetable with FDA-approved cysteine-promoting compounds + and could synergize with glucose-lowering treatments, including the ketogenic + diet, for GBM.", "venue": "", "year": 2020, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://academic.oup.com/neuro-oncology/article-pdf/22/Supplement_2/ii221/34691304/noaa215.926.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2020-11-09", "journal": {"volume": + "22", "name": "Neuro-oncology"}, "authors": [{"authorId": "3913142", "name": + "E. Noch"}, {"authorId": "2065330100", "name": "L. Palma"}, {"authorId": "1716222698", + "name": "I. Yim"}, {"authorId": "1454461390", "name": "Bhavneet Binder"}, + {"authorId": "123664542", "name": "E. Benedetti"}, {"authorId": "2067285", + "name": "J. Krumsiek"}, {"authorId": "150097652", "name": "O. Elemento"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ec7a1d7d9e7122eefe417eb432c1b7876505964a", + "externalIds": {"MAG": "3083301001", "DOI": "10.1158/1538-7445.am2020-5712", + "CorpusId": 225364009}, "corpusId": 225364009, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/ec7a1d7d9e7122eefe417eb432c1b7876505964a", + "title": "Abstract 5712: Nutrient scarcity confers breast cancer brain metastasis + sensitivity to serine synthesis pathway inhibition", "abstract": null, "venue": + "", "year": 2020, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2020-08-15", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "5891999", "name": "B. Ngo"}, {"authorId": "115819822", "name": "Eugenie Kim"}, + {"authorId": "50535810", "name": "Sophia Doll"}, {"authorId": "1600820777", + "name": "Sophia Bustraan"}, {"authorId": "114311983", "name": "Alba Luengo"}, + {"authorId": "34711277", "name": "Shawn M. Davidson"}, {"authorId": "2157679423", + "name": "A. Ali"}, {"authorId": "4469681", "name": "G. Ferraro"}, {"authorId": + "8118329", "name": "Diane Kang"}, {"authorId": "1776165", "name": "Jing Ni"}, + {"authorId": "46875693", "name": "R. Liang"}, {"authorId": "1600820946", "name": + "Ariana Plasger"}, {"authorId": "4306515", "name": "Edward R. Kastenhuber"}, + {"authorId": "6108327", "name": "Roozbeh Eskandari"}, {"authorId": "145170581", + "name": "Sarah Bacha"}, {"authorId": "49408849", "name": "Roshan K. Sriram"}, + {"authorId": "40353456", "name": "Benjamin D. Stein"}, {"authorId": "3543494", + "name": "S. Bakhoum"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, + {"authorId": "3579975", "name": "M. Snuderl"}, {"authorId": "10006170", "name": + "N. Mainolfi"}, {"authorId": "2272920", "name": "Vipin Suri"}, {"authorId": + "2054407866", "name": "Adam J. Friedman"}, {"authorId": "47769189", "name": + "M. Manfredi"}, {"authorId": "1843680", "name": "D. Sabatini"}, {"authorId": + "151477189", "name": "Drew R. Jones"}, {"authorId": "145684949", "name": "Min + Yu"}, {"authorId": "50985038", "name": "Jean J. Zhao"}, {"authorId": "32514332", + "name": "R. Jain"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "144979479", "name": "M. Mann"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5141475", "name": "M. Pacold"}]}, {"paperId": "f64eef571470a633f345880527574314bfd4d63a", + "externalIds": {"PubMedCentral": "8034380", "MAG": "3096177766", "DOI": "10.1038/s41586-020-2901-9", + "CorpusId": 226060032, "PubMed": "33116299"}, "corpusId": 226060032, "publicationVenue": + {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/f64eef571470a633f345880527574314bfd4d63a", + "title": "Identification of SARS-CoV-2 Inhibitors using Lung and Colonic Organoids", + "abstract": null, "venue": "Nature", "year": 2020, "referenceCount": 36, "citationCount": + 281, "influentialCitationCount": 13, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/s41586-020-2901-9.pdf", "status": + null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2020-10-28", "journal": {"volume": "589", "pages": "270 + - 275", "name": "Nature"}, "authors": [{"authorId": "1678087048", "name": + "Yuling Han"}, {"authorId": "8121194", "name": "Xiaohua Duan"}, {"authorId": + "1733349662", "name": "Liuliu Yang"}, {"authorId": "1422205499", "name": "Benjamin + E. Nilsson-Payant"}, {"authorId": "152702655", "name": "Pengfei Wang"}, {"authorId": + "8751560", "name": "Fuyu Duan"}, {"authorId": "1687775322", "name": "Xuming + Tang"}, {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": "40543563", + "name": "Tuo Zhang"}, {"authorId": "88725738", "name": "S. Uhl"}, {"authorId": + "4785493", "name": "Y. Bram"}, {"authorId": "2006900424", "name": "Chanel + Richardson"}, {"authorId": "2144872721", "name": "Jiajun Zhu"}, {"authorId": + "2186108428", "name": "Zeping Zhao"}, {"authorId": "1682800", "name": "D. + Redmond"}, {"authorId": "145731038", "name": "S. Houghton"}, {"authorId": + "50652368", "name": "Duc-Huy T. Nguyen"}, {"authorId": "48207902", "name": + "Dong-Li Xu"}, {"authorId": "2144803226", "name": "Xing Wang"}, {"authorId": + "3503076", "name": "J. Jessurun"}, {"authorId": "3177215", "name": "A. Borczuk"}, + {"authorId": "2108678622", "name": "Yaoxing Huang"}, {"authorId": "145916288", + "name": "Jared L. Johnson"}, {"authorId": "47909573", "name": "Yuru Liu"}, + {"authorId": "118390923", "name": "J. Xiang"}, {"authorId": "2113635227", + "name": "Hui Wang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5462120", "name": "B. tenOever"}, {"authorId": "144705651", "name": "D. Ho"}, + {"authorId": "34160280", "name": "F. C. Pan"}, {"authorId": "144263094", "name": + "T. Evans"}, {"authorId": "2145302790", "name": "H. Chen"}, {"authorId": "46462360", + "name": "R. Schwartz"}, {"authorId": "47336157", "name": "Shuibing Chen"}]}, + {"paperId": "f7c7cf82bd09f7f4efa7cf9fd3f4318fcae32717", "externalIds": {"MAG": + "3004281696", "DOI": "10.1002/cne.24956", "CorpusId": 213031990, "PubMed": + "32449185"}, "corpusId": 213031990, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/f7c7cf82bd09f7f4efa7cf9fd3f4318fcae32717", + "title": "Distribution and localization of phosphatidylinositol 5-phosphate, + 4-kinase alpha and beta in the brain", "abstract": "Phosphatidylinositol-4,5-bisphosphate + (PI-4,5-P2) is critical for synaptic vesicle docking and fusion and generation + of the second messengers, diacylglycerol and inositol-1,4,5-trisphosphate. + PI-4,5-P2 can be generated by two families of kinases: type 1 phosphatidylinositol-4-phosphate + 5-kinases, encoded by PIP5K1A, PIP5K1B and PIP5K1C, and type 2 phosphatidylinositol-5-phosphate + 4-kinases, encoded by PIP4K2A, PIP4K2B, and PIP4K2C. While the roles of the + type 1 enzymes in brain function have been extensively studied, the roles + of the type 2 enzymes are poorly understood. Using selective antibodies validated + by genetic deletion of pip4k2a or pip4k2b in mouse brain, we characterized + the location of the enzymes, PI5P4K\u03b1 and PI5P4K\u00df, encoded by these + genes. In mice, we demonstrate that PI5P4K\u03b1 is expressed in adulthood, + whereas PI5P4K\u00df is expressed early in development. PI5P4K\u03b1 localizes + to white matter tracts, especially the corpus callosum, and at a low level + in neurons, while PI5P4K\u00df is expressed in neuronal populations, especially + hippocampus and cortex. Dual labeling studies demonstrate that PI5P4K\u03b1 + co-localizes with the oligodendrocyte marker, Olig2, whereas PI5P4K\u00df + co-localizes with the neuronal marker, NeuN. Immunohistochemical subcellular + distribution studies demonstrate that PI5P4K\u03b1 and PI5P4K\u00df are expressed + in the early endosome system. Ultrastructural analysis demonstrates that both + kinases are contained in axon terminals and dendritic spines adjacent to the + synaptic membrane, which support a potential role in synaptic transmission. + Immunohistochemical analysis of macaque and human brain tissue demonstrate + a conserved pattern for PI5P4K\u03b1 and PI5P4K\u00df. These results highlight + the diverse cell-autonomous expression of PI5P4K\u03b1 and PI5P4K\u00df and + support further exploration into their role in synaptic function in the brain.", + "venue": "bioRxiv", "year": 2020, "referenceCount": 68, "citationCount": 3, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry", "Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Biology", + "source": "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2020-01-30", "journal": {"name": "bioRxiv"}, "authors": + [{"authorId": "3913142", "name": "E. Noch"}, {"authorId": "121514578", "name": + "Isaiah Yim"}, {"authorId": "1732734", "name": "T. Milner"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "fddab39eee67d11d7abb392232baafd01fa191f1", + "externalIds": {"MAG": "3033691847", "DOI": "10.1101/2020.06.04.135087", "CorpusId": + 219603961}, "corpusId": 219603961, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/fddab39eee67d11d7abb392232baafd01fa191f1", + "title": "Age-induced methylmalonic acid accumulation promotes tumor progression + and aggressiveness", "abstract": "From age 65 onwards, the risk of cancer + incidence and associated mortality is substantially higher1-3. Nonetheless, + our understanding of the complex relationship between age and cancer is still + in its infancy4. For decades, the link has largely been attributed to increased + exposure time to mutagens in older individuals. However, this view does not + account for the well-established role of diet, exercise and small molecules + that target the pace of metabolic aging5-8. Here, we show that metabolic alterations + that occur with age can render a systemic environment favorable to progression + and aggressiveness of tumors. Specifically, we show that methylmalonic acid + (MMA), a by-product of propionate metabolism, is significantly up-regulated + in the serum of older people, and functions as a mediator of tumor progression. + We traced this to the induction of SOX4 and a consequent transcriptional reprogramming + that can endow cancer cells with aggressive properties. Thus, accumulation + of MMA represents a novel link between aging and cancer progression, implicating + MMA as a novel therapeutic target for advanced carcinomas.", "venue": "bioRxiv", + "year": 2020, "referenceCount": 49, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.biorxiv.org/content/biorxiv/early/2020/06/05/2020.06.04.135087.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2020-06-05", "journal": {"name": "bioRxiv"}, "authors": + [{"authorId": "2087116099", "name": "Ana P Gomes"}, {"authorId": "3324022", + "name": "Didem Ilter"}, {"authorId": "121128193", "name": "V. Low"}, {"authorId": + "83689245", "name": "J. Endress"}, {"authorId": "52621189", "name": "J. Fern\u00e1ndez-Garc\u00eda"}, + {"authorId": "1887417083", "name": "A. Rosenzweig"}, {"authorId": "50356549", + "name": "Tanya Schild"}, {"authorId": "11236293", "name": "D. Broekaert"}, + {"authorId": "1887422976", "name": "Adnan Ahmed"}, {"authorId": "8444258", + "name": "M. Planque"}, {"authorId": "2382021", "name": "Ilaria Elia"}, {"authorId": + "1886508939", "name": "Julie Han"}, {"authorId": "1887752916", "name": "Charles + G. Kinzig"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": + "5135907", "name": "A. Mutvei"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "144285023", "name": "R. de Cabo"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4622316", "name": "Noah Dephoure"}, {"authorId": + "46775302", "name": "S. Fendt"}, {"authorId": "4037343", "name": "J. Blenis"}]}, + {"paperId": "01c94cb91a94a7683b2ce5dd444f33fb1357b7c3", "externalIds": {"MAG": + "2946677666", "DOI": "10.1093/ANNONC/MDZ095", "CorpusId": 181760896, "PubMed": + "32084703"}, "corpusId": 181760896, "publicationVenue": {"id": "9777e708-5066-48fd-ab6a-57496cbca033", + "name": "Annals of Oncology", "type": "journal", "alternate_names": ["Ann + Oncol"], "issn": "0923-7534", "url": "https://academic.oup.com/annonc/issue", + "alternate_urls": ["http://annonc.oxfordjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/01c94cb91a94a7683b2ce5dd444f33fb1357b7c3", + "title": "Double PIK3CA mutations in cis enhance PI3K\u03b1 oncogene activation + and sensitivity to PI3K\u03b1 inhibitors in breast cancer.", "abstract": null, + "venue": "Annals of Oncology", "year": 2019, "referenceCount": 0, "citationCount": + 3, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.annalsofoncology.org/article/S092375341930273X/pdf", "status": + null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-05-01", "journal": + {"volume": "30 Suppl 3", "pages": "\n iii1\n ", "name": "Annals + of oncology : official journal of the European Society for Medical Oncology"}, + "authors": [{"authorId": "35123724", "name": "N. Vasan"}, {"authorId": "3224289", + "name": "P. Razavi"}, {"authorId": "2157356093", "name": "J. Johnson"}, {"authorId": + "2959236", "name": "H. Shao"}, {"authorId": "145632788", "name": "E. Reznik"}, + {"authorId": "2149040221", "name": "M. Smith"}, {"authorId": "46517710", "name": + "R. Sebra"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1657637983", + "name": "M. Scaltriti"}, {"authorId": "66042490", "name": "J. Baselga"}]}, + {"paperId": "043a453e94a480bbf361e1eb4ffbedf8db30523e", "externalIds": {"MAG": + "2944155389", "PubMedCentral": "6551940", "DOI": "10.1210/JS.2019-SAT-LB057", + "CorpusId": 165053647}, "corpusId": 165053647, "publicationVenue": {"id": + "ccbeb193-d73e-4c27-9e78-65553fb9c08a", "name": "Journal of the Endocrine + Society", "type": "journal", "alternate_names": ["J Endocr Soc"], "issn": + "2472-1972", "url": "http://www.endocrine.org/endocrine-press/journals/open-access-journal"}, + "url": "https://www.semanticscholar.org/paper/043a453e94a480bbf361e1eb4ffbedf8db30523e", + "title": "SAT-LB057 High-Fructose Corn Syrup Enhances Intestinal Tumor Growth + in Mice", "abstract": "Abstract An increasing number of studies have suggested + a potential link between sugar consumption and cancer. However, a direct relationship + between the two remains controversial. Here, we treated APC-mutant mice daily + with a modest amount of high-fructose corn syrup (HFCS) via oral gavage to + mimic sugar-sweetened beverage (SSB) consumption and evaluated the effects + of SSBs on intestinal tumorigenesis. We observed a dramatic increase in tumor + size and tumor grade in HFCS-treated mice despite no signs of obesity or metabolic + syndrome. A bolus of HFCS spikes the level of fructose and glucose in the + intestinal lumen and serum, respectively, allowing tumors to take up both + sugars efficiently. Ketohexokinase (KHK) in tumors rapidly converts fructose + to fructose-1-phosphate (F1P), lowering cytosolic ATP in the process. Consequently, + this leads to the activation of glycolysis as ATP depletion relieves the allosteric + inhibition of phosphofructokinase (PFK), the most critical regulatory enzyme + in glycolysis. This accelerated glycolysis contributes to the increased de + novo lipogenesis pathway that enhances tumor growth in HFCS-treated mice. + Importantly, the deletion of KHK or fatty acid synthase (FASN) in APC-mutant + mice abolishes the HFCS-induced metabolic changes and tumor growth. Overall, + our results provide a mechanistic rationale for restricting SSB consumption + to decrease the rate of growth of early stage colorectal cancers. Unless otherwise + noted, all abstracts presented at ENDO are embargoed until the date and time + of presentation. For oral presentations, the abstracts are embargoed until + the session begins. Abstracts presented at a news conference are embargoed + until the date and time of the news conference. The Endocrine Society reserves + the right to lift the embargo on specific abstracts that are selected for + promotion prior to or during ENDO.", "venue": "Journal of the Endocrine Society", + "year": 2019, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2019-04-15", "journal": {"volume": "3", "name": "Journal of the Endocrine + Society"}, "authors": [{"authorId": "145524334", "name": "M. Goncalves"}, + {"authorId": "7434113", "name": "Changyuan Lu"}, {"authorId": "32250589", + "name": "T. Hartman"}, {"authorId": "4151944", "name": "Seo-Kyoung Hwang"}, + {"authorId": "34187590", "name": "C. Pauli"}, {"authorId": "2110994237", "name": + "Samuel R Taylor"}, {"authorId": "5769141", "name": "S. Gross"}, {"authorId": + "4097554", "name": "K. Rhee"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "40164091", "name": "Jihye Yun"}]}, {"paperId": "0807ee160b498717eac4489e1c0444eb23a4faa9", + "externalIds": {"MAG": "2920641325", "DOI": "10.1146/ANNUREV-CANCERBIO-030518-055855", + "CorpusId": 86678376}, "corpusId": 86678376, "publicationVenue": {"id": "4c63af56-3e48-4bc9-a971-0d19a9b932e5", + "name": "Annual Review of Cancer Biology", "alternate_names": ["Annu Rev Cancer + Biology"], "issn": "2472-3428", "url": "https://www.annualreviews.org/journal/cancerbio"}, + "url": "https://www.semanticscholar.org/paper/0807ee160b498717eac4489e1c0444eb23a4faa9", + "title": "Dietary Fat and Sugar in Promoting Cancer Development and Progression", + "abstract": "The uncontrolled cellular growth that characterizes tumor formation + requires a constant delivery of nutrients. Since the 1970s, researchers have + wondered if the supply of nutrients from the diet could impact tumor development. + Numerous studies have assessed the impact of dietary components, specifically + sugar and fat, to increased cancer risk. For the most part, data from these + trials have been inconclusive; however, this does not indicate that dietary + factors do not contribute to cancer progression. Rather, the dietary contribution + may be dependent on tumor, patient, and context, making it difficult to detect + in the setting of large trials. In this review, we combine data from prospective + cohort trials with mechanistic studies in mice to argue that fat and sugar + can play a role in tumorigenesis and disease progression. We find that certain + tumors may respond directly to dietary sugar (colorectal and endometrial cancers) + and fat (prostate cancer) or indirectly to the obese state (breast cancer).", + "venue": "Annual Review of Cancer Biology", "year": 2019, "referenceCount": + 143, "citationCount": 19, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.annualreviews.org/doi/pdf/10.1146/annurev-cancerbio-030518-055855", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review"], + "publicationDate": "2019-03-04", "journal": {"name": "Annual Review of Cancer + Biology"}, "authors": [{"authorId": "145524334", "name": "M. Goncalves"}, + {"authorId": "48821307", "name": "B. Hopkins"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "095e393ccfe2e8379e167f3d9268c75626acc2d6", "externalIds": + {"MAG": "2936445722", "DOI": "10.1021/acs.jproteome.8b00969", "CorpusId": + 106408394, "PubMed": "30964683"}, "corpusId": 106408394, "publicationVenue": + {"id": "c7bbca07-9604-48a6-85d8-512fa663722e", "name": "Journal of Proteome + Research", "type": "journal", "alternate_names": ["J Proteome Res"], "issn": + "1535-3893", "url": "https://pubs.acs.org/journal/jprobs", "alternate_urls": + ["http://pubs.acs.org/journals/jprobs/", "http://pubs.acs.org/journals/jprobs/index.html", + "http://pubs.acs.org/journal/jprobs"]}, "url": "https://www.semanticscholar.org/paper/095e393ccfe2e8379e167f3d9268c75626acc2d6", + "title": "Mapping Post-Translational Modifications of de Novo Purine Biosynthetic + Enzymes: Implications for Pathway Regulation.", "abstract": "Purines represent + a class of essential metabolites produced by the cell to maintain cellular + homeostasis and facilitate cell proliferation. In times of high purine demand, + the de novo purine biosynthetic pathway is activated; however, the mechanisms + that facilitate this process are largely unknown. One plausible mechanism + is through intracellular signaling, which results in enzymes within the pathway + becoming post-translationally modified to enhance their individual enzyme + activities and the overall pathway metabolic flux. Here, we employ a proteomic + strategy to investigate the extent to which de novo purine biosynthetic pathway + enzymes are post-translationally modified in 293T cells. We identified 7 post-translational + modifications on 135 residues across the 6 human pathway enzymes. We further + asked whether there were differences in the post-translational modification + state of each pathway enzyme isolated from cells cultured in the presence + or absence of purines. Of the 174 assigned modifications, 67% of them were + only detected in one experimental growth condition in which a significant + number of serine and threonine phosphorylations were noted. A survey of the + most-probable kinases responsible for these phosphorylation events uncovered + a likely AKT phosphorylation site at residue Thr397 of PPAT, which was only + detected in cells under purine-supplemented growth conditions. These data + suggest that this modification might alter enzyme activity or modulate its + interaction(s) with downstream pathway enzymes. Together, these findings propose + a role for post-translational modifications in pathway regulation and activation + to meet intracellular purine demand.", "venue": "Journal of Proteome Research", + "year": 2019, "referenceCount": 50, "citationCount": 7, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://figshare.com/articles/journal_contribution/Mapping_Post-Translational_Modifications_of_de_Novo_Purine_Biosynthetic_Enzymes_Implications_for_Pathway_Regulation/8009564/1/files/14921753.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle", "Review"], "publicationDate": "2019-04-09", + "journal": {"volume": "18 5", "pages": "\n 2078-2087\n ", + "name": "Journal of proteome research"}, "authors": [{"authorId": "2927467", + "name": "Chunlian Liu"}, {"authorId": "2667612", "name": "G. Knudsen"}, {"authorId": + "5480995", "name": "Anthony M. Pedley"}, {"authorId": "2000159002", "name": + "Jingxuan He"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "5247030", "name": "Tomer M. Yaron"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "6523855", "name": "S. Benkovic"}]}, {"paperId": "14fed95b45bd5925f1e4d5374cfab78bb7b8e067", + "externalIds": {"PubMedCentral": "6941320", "MAG": "2964136203", "DOI": "10.1101/714196", + "CorpusId": 199629307, "PubMed": "31908776"}, "corpusId": 199629307, "publicationVenue": + {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": "bioRxiv", "type": + "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/14fed95b45bd5925f1e4d5374cfab78bb7b8e067", + "title": "Tissue of origin dictates GOT1 dependence and confers synthetic + lethality to radiotherapy", "abstract": "BackgroundMetabolic programs in cancer + cells are influenced by genotype and the tissue of origin. We have previously + shown that central carbon metabolism is rewired in pancreatic ductal adenocarcinoma + (PDA) to support proliferation through a glutamate oxaloacetate transaminase + 1 (GOT1)-dependent pathway.MethodsWe utilized a doxycycline-inducible shRNA-mediated + strategy to knockdown GOT1 in PDA and colorectal cancer (CRC) cell lines and + tumor models of similar genotype. These cells were analyzed for the ability + to form colonies and tumors to test if tissue type impacted GOT1 dependence. + Additionally, the ability of GOT1 to impact the response to chemo- and radiotherapy + was assessed. Mechanistically, the associated specimens were examined using + a combination of steady-state and stable isotope tracing metabolomics strategies + and computational modeling. Statistics were calculated using GraphPad Prism + 7. One-way ANOVA was performed for experiments comparing multiple groups with + one changing variable. Student\u2019s t test (unpaired, two-tailed) was performed + when comparing two groups to each other. Metabolomics data comparing three + PDA and three CRC cell lines were analyzed by performing Student\u2019s t + test (unpaired, two-tailed) between all PDA metabolites and CRC metabolites.ResultsWhile + PDA exhibits profound growth inhibition upon GOT1 knockdown, we found CRC + to be insensitive. In PDA, but not CRC, GOT1 inhibition disrupted glycolysis, + nucleotide metabolism, and redox homeostasis. These insights were leveraged + in PDA, where we demonstrate that radiotherapy potently enhanced the effect + of GOT1 inhibition on tumor growth.ConclusionsTaken together, these results + illustrate the role of tissue type in dictating metabolic dependencies and + provide new insights for targeting metabolism to treat PDA.", "venue": "bioRxiv", + "year": 2019, "referenceCount": 68, "citationCount": 19, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://cancerandmetabolism.biomedcentral.com/counter/pdf/10.1186/s40170-019-0202-2", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-07-25", "journal": + {"volume": "8", "name": "Cancer & Metabolism"}, "authors": [{"authorId": "2053022852", + "name": "Barbara S. Nelson"}, {"authorId": "49478108", "name": "Lin Lin"}, + {"authorId": "40237579", "name": "D. Kremer"}, {"authorId": "48247953", "name": + "C. Sousa"}, {"authorId": "1397966521", "name": "Cecilia Cotta-Ramusino"}, + {"authorId": "35171451", "name": "Amy L. Myers"}, {"authorId": "2069856065", + "name": "Johanna Ramos"}, {"authorId": "1491340265", "name": "Tina Gao"}, + {"authorId": "2058928795", "name": "I. Kovalenko"}, {"authorId": "1401906161", + "name": "K. Wilder-Romans"}, {"authorId": "39740614", "name": "Joseph J. Dresser"}, + {"authorId": "29884234", "name": "Mary A Davis"}, {"authorId": "49923389", + "name": "Ho-Joon Lee"}, {"authorId": "152709401", "name": "Z. Nwosu"}, {"authorId": + "11184021", "name": "Scott Campit"}, {"authorId": "13470228", "name": "Oksana + Mashadova"}, {"authorId": "4374034", "name": "Brandon Nicolay"}, {"authorId": + "4171577", "name": "Zachary P. Tolstyka"}, {"authorId": "7745600", "name": + "C. Halbrook"}, {"authorId": "39821422", "name": "S. Chandrasekaran"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "36509270", "name": "H. Crawford"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4668673", "name": + "A. Kimmelman"}, {"authorId": "35426517", "name": "D. Wahl"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}]}, {"paperId": "26a34f290fed39e7c904bb4c4f71fb2c86fdcbb9", + "externalIds": {"MAG": "2934863159", "DOI": "10.1016/j.chembiol.2019.02.015", + "CorpusId": 89619879, "PubMed": "30930164"}, "corpusId": 89619879, "publicationVenue": + {"id": "66a2a80a-90f1-4c5a-8798-1be97c318574", "name": "Cell Chemical Biology", + "alternate_names": ["Cell Chem Biology"], "issn": "2451-9456", "alternate_issns": + ["2451-9448"], "url": "https://www.sciencedirect.com/journal/cell-chemical-biology", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/24519456", + "http://www.sciencedirect.com/science/journal/24519456/23/"]}, "url": "https://www.semanticscholar.org/paper/26a34f290fed39e7c904bb4c4f71fb2c86fdcbb9", + "title": "Discovery of Covalent CDK14 Inhibitors with Pan-TAIRE Family Specificity.", + "abstract": null, "venue": "Cell Chemical Biology", "year": 2019, "referenceCount": + 52, "citationCount": 15, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S2451945619300704/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2019-06-01", "journal": {"volume": + "26 6", "pages": "\n 804-817.e12\n ", "name": "Cell chemical + biology"}, "authors": [{"authorId": "11404167", "name": "F. M. Ferguson"}, + {"authorId": "47040242", "name": "Zainab M. Doctor"}, {"authorId": "2297254", + "name": "S. Ficarro"}, {"authorId": "39374687", "name": "Christopher M Browne"}, + {"authorId": "2605597", "name": "J. Marto"}, {"authorId": "145916288", "name": + "Jared L. Johnson"}, {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "7473112", "name": "N. Kim"}, + {"authorId": "35668012", "name": "T. Sim"}, {"authorId": "90357718", "name": + "Matthew J. Berberich"}, {"authorId": "10019624", "name": "M. Kalocsay"}, + {"authorId": "2940596", "name": "P. Sorger"}, {"authorId": "3977406", "name": + "N. Gray"}]}, {"paperId": "327f1fd849443381b07c6d3544e90153fa7812c6", "externalIds": + {"MAG": "2955592227", "DOI": "10.1158/1538-7445.SABCS18-2062", "CorpusId": + 198353844}, "corpusId": 198353844, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/327f1fd849443381b07c6d3544e90153fa7812c6", + "title": "Abstract 2062: Evaluating the effect of tumor necrosis on glycolytic + flux and cell survival in glioblastoma", "abstract": null, "venue": "Molecular + and Cellular Biology / Genetics", "year": 2019, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Physics", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2019-07-01", "journal": {"name": + "Molecular and Cellular Biology / Genetics"}, "authors": [{"authorId": "3913142", + "name": "E. Noch"}, {"authorId": "121514578", "name": "Isaiah Yim"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "3952921a53f246c6cc92ac59dd5a28559a659539", + "externalIds": {"CorpusId": 201685302}, "corpusId": 201685302, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/3952921a53f246c6cc92ac59dd5a28559a659539", + "title": "PIP 4 Ks Suppress Insulin S ignaling through a Catalytic-Independent + Mechanism Graphical", "abstract": null, "venue": "", "year": 2019, "referenceCount": + 46, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "152325571", + "name": "Diana G. Wang"}, {"authorId": "4422893", "name": "M. Paddock"}, {"authorId": + "49142390", "name": "Mark R. Lundquist"}, {"authorId": "2110677133", "name": + "Janet Y. Sun"}, {"authorId": "13470228", "name": "Oksana Mashadova"}, {"authorId": + "51160946", "name": "Solomon C. Amadiume"}, {"authorId": "15205001", "name": + "Timothy W. Bumpus"}, {"authorId": "7331238", "name": "Cindy Hodakoski"}, + {"authorId": "48821307", "name": "B. Hopkins"}, {"authorId": "48771941", "name": + "Matthew Fine"}, {"authorId": "2072855104", "name": "Amanda Hill"}, {"authorId": + "2115865796", "name": "T. Yang"}, {"authorId": "4863571", "name": "Jeremy + M. Baskin"}, {"authorId": "3918769", "name": "L. Dow"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "3c1320342cfeb3aa51c22b8938467f991bea7331", + "externalIds": {"MAG": "2952013696", "DOI": "10.1016/j.ccell.2019.05.002", + "CorpusId": 206529595, "PubMed": "31185214"}, "corpusId": 206529595, "publicationVenue": + {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", "name": "Cancer Cell", "type": + "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/3c1320342cfeb3aa51c22b8938467f991bea7331", + "title": "Non-oncogene Addiction to SIRT3 Plays a Critical Role in Lymphomagenesis.", + "abstract": null, "venue": "Cancer Cell", "year": 2019, "referenceCount": + 98, "citationCount": 54, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1535610819302405/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2019-06-01", "journal": {"volume": + "35 6", "pages": "\n 916-931.e9\n ", "name": "Cancer cell"}, + "authors": [{"authorId": "50651874", "name": "Meng Li"}, {"authorId": "50462482", + "name": "Ying-Ling Chiang"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "79496189", "name": "Matt Teater"}, {"authorId": "47728412", + "name": "J. Hong"}, {"authorId": "2110770666", "name": "Hao Shen"}, {"authorId": + "2151978477", "name": "Ling Wang"}, {"authorId": "2118517499", "name": "Jing + Hu"}, {"authorId": "145782282", "name": "Hui Jing"}, {"authorId": "1410160150", + "name": "Zhengming Chen"}, {"authorId": "50399566", "name": "N. Jain"}, {"authorId": + "145546240", "name": "C. Duy"}, {"authorId": "36529561", "name": "S. Mistry"}, + {"authorId": "6791438", "name": "L. Cerchietti"}, {"authorId": "4001772", + "name": "J. Cross"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144362061", "name": "Michael R. Green"}, {"authorId": "35643033", "name": + "Hening Lin"}, {"authorId": "145150236", "name": "A. Melnick"}]}, {"paperId": + "3cebf7ca2285f3b768c94019b39170d3d3c42917", "externalIds": {"MAG": "2953450966", + "DOI": "10.1158/1538-7445.AM2019-3917", "CorpusId": 219269535}, "corpusId": + 219269535, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/3cebf7ca2285f3b768c94019b39170d3d3c42917", + "title": "Abstract 3917: DoublePIK3CAmutations incisenhance oncogene activation + and sensitivity to PI3K alpha inhibitors in breast cancer", "abstract": "Activating + mutations in PIK3CA, the gene coding for the catalytic subunit (p110\u03b1) + of phosphoinositide 3-kinase (PI3K), are the most frequent oncogenic alterations + in all cancers, including estrogen receptor-positive (ER+) breast cancer. + There are many distinct oncogenic PIK3CA mutations including major hotspot + mutations (e.g. E542K, E545K, H1047R) which are predictive of response to + PI3K\u03b1 inhibitors. While responses to PI3K\u03b1 inhibitors can be variable, + some patients with single hotspot mutant tumors derive a deep and prolonged + clinical benefit. In a comprehensive analysis of the genomic data available + in breast cancer, we observed double PIK3CA mutations and investigated their + potential biological relevance and potential correlation with sensitivity + to PI3K\u03b1 inhibitors. We detected double PIK3CA mutations in 10-15% of + all PIK3CA-mutant cancers including breast cancer. Double PIK3CA mutations + in breast cancer are defined by a pattern of co-expression of a major hotspot + mutation associated with a recurrent second-site PIK3CA mutation (\u2018minor + mutation\u2019). We have found that these double PIK3CA mutations are compound, + that is in cis on the same allele, using single molecule real time sequencing + (SMRT-seq) of fresh breast tumor samples. Double compound PIK3CA mutations + result in increased PI3K activity and downstream signaling compared to single + hotspot mutants in nontransformed cells and in ER+ breast cancer cells. Double + compound mutations also increase cell proliferation and xenograft growth compared + to single hotspot mutants. Biochemical experiments using recombinant PI3K + compound mutant protein complexes reveal a combination mechanism of action, + with simultaneous PI3K destabilization and increased membrane binding compared + to single hotspot mutants, leading to increased kinase activity. Importantly, + these compound mutations predict for increased sensitivity to PI3K\u03b1 inhibitors + compared to single hotspot mutants in both preclinical models and also in + patients with breast cancer. Together, our data support that double compound + PIK3CA mutations enhance the oncogenicity of single hotspot PIK3CA mutations + and this increased dependency results in increased sensitivity to PI3K\u03b1 + inhibitors compared to single hotspot mutations. We propose that double compound + activating mutations are an additional mechanism of oncogenic transformation + in addition to other known mechanisms such as gene amplification, point mutation, + or gene translocation. We speculate that double compound mutant PIK3CA may + function as a clinical biomarker of increased sensitivity to PI3K-directed + targeted therapies and may improve the therapeutic window of PI3K inhibitors + in ER+ breast cancer and other PIK3CA-mutant tumor histologies. Citation Format: + Neil Vasan, Pedram Razavi, Jared Johnson, Hong Shao, Hardik Shah, Alesia Antoine, + Erik Ladewig, Alexander Gorelick, Eneda Toska, Guotai Xu, Abiha Kazmi, Matthew + T. Chang, Barry S. Taylor, Maura N. Dickler, Komal Jhaveri, Raul Rabadan, + Ed Reznik, Melissa L. Smith, Robert Sebra, Lewis C. Cantley, Maurizio Scaltriti, + Jose Baselga. Double PIK3CA mutations in cis enhance oncogene activation and + sensitivity to PI3K alpha inhibitors in breast cancer [abstract]. In: Proceedings + of the American Association for Cancer Research Annual Meeting 2019; 2019 + Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 + Suppl):Abstract nr 3917.", "venue": "Experimental and Molecular Therapeutics", + "year": 2019, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2019-07-01", "journal": {"name": "Experimental and Molecular Therapeutics"}, + "authors": [{"authorId": "35123724", "name": "N. Vasan"}, {"authorId": "3224289", + "name": "P. Razavi"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, + {"authorId": "2959236", "name": "H. Shao"}, {"authorId": "49820132", "name": + "H. Shah"}, {"authorId": "49335811", "name": "Alesia Antoine"}, {"authorId": + "3139198", "name": "Erik Ladewig"}, {"authorId": "48892954", "name": "A. Gorelick"}, + {"authorId": "4733908", "name": "E. Toska"}, {"authorId": "51290929", "name": + "Guotai Xu"}, {"authorId": "150907238", "name": "Abiha Kazmi"}, {"authorId": + "2141904248", "name": "Matthew T. Chang"}, {"authorId": "36898514", "name": + "B. Taylor"}, {"authorId": "4713308", "name": "M. Dickler"}, {"authorId": + "47352468", "name": "K. Jhaveri"}, {"authorId": "40620158", "name": "R. Rabad\u00e1n"}, + {"authorId": "145632788", "name": "E. Reznik"}, {"authorId": "2116670076", + "name": "M. Smith"}, {"authorId": "46517710", "name": "R. Sebra"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "8336319", "name": "M. Scaltriti"}, + {"authorId": "144806171", "name": "J. Baselga"}]}, {"paperId": "4267d68ed03ff01b3144bb4a2c133a8196745624", + "externalIds": {"MAG": "2982032674", "DOI": "10.1101/819961", "CorpusId": + 208589901}, "corpusId": 208589901, "publicationVenue": {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", + "name": "bioRxiv", "type": "journal", "url": "http://biorxiv.org/"}, "url": + "https://www.semanticscholar.org/paper/4267d68ed03ff01b3144bb4a2c133a8196745624", + "title": "Targeting the PI5P4K lipid kinase family in cancer using novel covalent + inhibitors", "abstract": "The PI5P4Ks have been demonstrated to be important + for cancer cell proliferation and other diseases. However, the therapeutic + potential of targeting these kinases is understudied due to a lack of potent, + specific small molecules available. Here we present the discovery and characterization + of a novel pan-PI5P4K inhibitor, THZ-P1-2, that covalently targets cysteines + on a disordered loop in PI5P4K\u03b1/\u03b2/\u03b3. THZ-P1-2 demonstrates + cellular on-target engagement with limited off-targets across the kinome. + AML/ALL cell lines were sensitive to THZ-P1-2, consistent with PI5P4K\u2019s + reported role in leukemogenesis. THZ-P1-2 causes autophagosome clearance defects + and upregulation in TFEB nuclear localization and target genes, disrupting + autophagy in a covalent-dependent manner and phenocopying the effects of PI5P4K + genetic deletion. Our studies demonstrate that PI5P4Ks are tractable targets, + with THZ-P1-2 as a useful tool to further interrogate the therapeutic potential + of PI5P4K inhibition and inform drug discovery campaigns for these lipid kinases + in cancer metabolism and other autophagy-dependent disorders.", "venue": "bioRxiv", + "year": 2019, "referenceCount": 59, "citationCount": 2, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.biorxiv.org/content/biorxiv/early/2019/10/25/819961.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2019-10-25", "journal": {"name": + "bioRxiv"}, "authors": [{"authorId": "6443517", "name": "S. Sivakumaren"}, + {"authorId": "13574443", "name": "Hyeseok Shim"}, {"authorId": "2262535", + "name": "Tinghu Zhang"}, {"authorId": "11404167", "name": "F. M. Ferguson"}, + {"authorId": "49142390", "name": "Mark R. Lundquist"}, {"authorId": "39374687", + "name": "Christopher M Browne"}, {"authorId": "91486080", "name": "H. Seo"}, + {"authorId": "4422893", "name": "M. Paddock"}, {"authorId": "16018077", "name": + "Theresa D. Manz"}, {"authorId": "7864101", "name": "Baishan Jiang"}, {"authorId": + "11796890", "name": "Mingfeng Hao"}, {"authorId": "50822194", "name": "P. + Krishnan"}, {"authorId": "152325571", "name": "Diana G. Wang"}, {"authorId": + "2115865796", "name": "T. Yang"}, {"authorId": "6254222", "name": "Nicholas + Kwiatkowski"}, {"authorId": "2297254", "name": "S. Ficarro"}, {"authorId": + "36406440", "name": "J. Cunningham"}, {"authorId": "2605597", "name": "J. + Marto"}, {"authorId": "1400570681", "name": "S. Dhe-Paganon"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3977406", "name": "N. Gray"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '290174' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:37 GMT + Via: + - 1.1 ed11c0a911869eff1368d11d64377b4a.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - yCPoYoMADd9yM08JH1feHIE4ZOd_GaL8A9UdPVfcUzTd7q2FGwPQcg== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOZiG9JPHcFTuA= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '290174' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:37 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - 7186b853-7f56-4736-8f61-d382a4a53781 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=100&limit=100 + response: + body: + string: '{"offset": 100, "next": 200, "data": [{"paperId": "545b1417bcc9098925a34151cd069f2114481cce", + "externalIds": {"MAG": "2913208997", "DOI": "10.1194/jlr.S092130", "CorpusId": + 73416527, "PubMed": "30718284"}, "corpusId": 73416527, "publicationVenue": + {"id": "1bf7bea6-6d70-4600-bae6-dbe7ac74bc80", "name": "Journal of Lipid Research", + "type": "journal", "alternate_names": ["J Lipid Res"], "issn": "0022-2275", + "url": "https://www.jlr.org/", "alternate_urls": ["http://www.jlr.org/", "http://www.jlr.org/contents-by-date.0.shtml"]}, + "url": "https://www.semanticscholar.org/paper/545b1417bcc9098925a34151cd069f2114481cce", + "title": "Treating cancer with phosphatidylinositol-3-kinase inhibitors: increasing + efficacy and overcoming resistance", "abstract": "The discovery of the phosphatidylinositol-3-kinase + (PI3K) pathway was a major advance in understanding growth factor signaling. + The high frequency of PI3K pathway mutations in many cancers has encouraged + a new field targeting cancer driver mutations. Although there have been many + successes, targeting PI3K itself has proven challenging, in part because of + its multiple isoforms with distinct roles. Despite promising preclinical results, + development of PI3K inhibitors as pharmacologic anticancer agents has been + limited by modest single-agent efficacy and significant adverse effects. If + we could overcome these limitations, PI3K inhibitors would be a powerful cancer-fighting + tool. Data from phase III clinical trials yields insight into some of the + problems with PI3K inhibitors. Recent advances have shed light on the mechanisms + of tumor resistance to PI3K inhibitors via feedback pathways that cause elevated + insulin levels that then activate the same PI3K pathways that are the targets + of inhibition. Improving our understanding of the complex regulatory feedback + pathways that activate in response to PI3K inhibition will reveal ways to + increase the efficacy of PI3K inhibitors and reduce adverse effects, increasing + the usefulness of this class as a treatment option for multiple cancer types. + Graphical Abstract", "venue": "Journal of Lipid Research", "year": 2019, "referenceCount": + 36, "citationCount": 12, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jlr.org/content/60/4/747.full.pdf", "status": + null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-02-04", "journal": + {"volume": "60", "pages": "747 - 752", "name": "Journal of Lipid Research"}, + "authors": [{"authorId": "4422893", "name": "M. Paddock"}, {"authorId": "123039768", + "name": "S. Field"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "5e7ef7cefc2799b7b0bc9155b7273d9d59798e3f", "externalIds": {"CorpusId": 198974721}, + "corpusId": 198974721, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/5e7ef7cefc2799b7b0bc9155b7273d9d59798e3f", + "title": "Vulnerabilities of PTEN \u2013 TP 53-Defi cient Prostate Cancers + to Compound PARP \u2013 PI 3 K Inhibition", "abstract": "Prostate cancer is + the most prevalent cancer in males, and treatment options are limited for + advanced forms of the disease. Loss of the PTEN and TP53 tumor suppressor + genes is commonly observed in prostate cancer, whereas their compound loss + is often observed in advanced prostate cancer. Here, we show that PARP inhibition + triggers a p53-dependent cellular senescence in a PTEN -defi cient setting + in the prostate. Surprisingly, we also fi nd that PARPinduced cellular senescence + is morphed into an apoptotic response upon compound loss of PTEN and p53. + We further show that superactivation of the prosurvival PI3K\u2013AKT signaling + pathway limits the effi cacy of a PARP single-agent treatment, and that PARP + and PI3K inhibitors effectively synergize to suppress tumorigenesis in human + prostate cancer cell lines and in a Pten / Trp53 \u2013defi cient mouse model + of advanced prostate cancer. Our fi ndings, therefore, identify a combinatorial + treatment with PARP and PI3K inhibitors as an effective option for PTEN -defi + cient prostate cancer. SIGNIFICANCE: The paucity of therapeutic options in + advanced prostate cancer displays an urgent need for the preclinical assessment + of novel therapeutic strategies. We identifi ed differential therapeutic vulnerabilities + that emerge upon the loss of both PTEN and p53, and observed that combined + inhibition of PARP and PI3K provides increased effi cacy in hormone-insensitive + advanced prostate cancer. Cancer Discov; 4(8); 896\u2013904. \u00a92014 AACR. + Authors\u2019 Affi liations: 1 Cancer Research Institute, Beth Israel Deaconess + Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess + Medical Center, Harvard Medical School; 2 Department of Medicine; Divisions + of 3 Hematology/Oncology and 4 Signal Transduction, Department of Medicine; + 5 Preclinical Murine Pharmacogenetics Facility, Beth Israel Deaconess Medical + Center; 6 Department of Pathology, Brigham and Women\u2019s Hospital; 7 Department + of Systems Biology, Harvard Medical School; 8 Center for Molecular Oncologic + Pathology; 9 Department of Medical Oncology, Dana-Farber Cancer Institute, + Boston; 10 Broad Institute of Harvard and Massachusetts Institute of Technology, + Cambridge, Massachusetts; and 11 On leave of absence: Servicio de Hematolog\u00eda + y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Murcia, + Spain Note: Supplementary data for this article are available at Cancer Discovery + Online (http://cancerdiscovery.aacrjournals.org/). E. Gonz\u00e1lez-Billalabeitia + and N. Seitzer contributed equally to this work. Corresponding Author: Pier + Paolo Pandolfi , Cancer Genetics Program, Beth Israel Deaconess Cancer Center, + Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical + School, 330 Brookline Avenue, Boston, MA 02215. Phone: 617-735-2121/2141; + Fax: 617-735-2120; E-mail: ppandolf@bidmc.harvard.edu doi: 10.1158/2159-8290.CD-13-0230 + \u00a92014 American Association for Cancer Research. INTRODUCTION There is + an urgent need for the development of novel successful strategies for advanced + prostate cancer to improve patient outcomes ( 1, 2 ). The loss of at least + one allele of phosphatase and tensin homolog deleted on chromosome 10 ( PTEN + ) is observed in more than 40% of prostate cancers ( 3, 4 ). As a lipid phosphatase, + PTEN suppresses the activation of the PI3K\u2013AKT signaling cascade that + is a central proto-oncogenic signaling on June 11, 2019. \u00a9 2014 American + Association for Cancer Research. cancerdiscovery.aacrjournals.org Downloaded + from Published OnlineFirst May 27, 2014; DOI: 10.1158/2159-8290.CD-13-0230", + "venue": "", "year": 2019, "referenceCount": 23, "citationCount": 4, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Medicine", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "1398122926", "name": "E. Gonzalez-Billalabeitia"}, + {"authorId": "3793357", "name": "N. Seitzer"}, {"authorId": "9673009", "name": + "S. Song"}, {"authorId": "2967391", "name": "M. Song"}, {"authorId": "40501341", + "name": "A. Patnaik"}, {"authorId": "8015447", "name": "Xue-Song Liu"}, {"authorId": + "4276612", "name": "M. Epping"}, {"authorId": "5380009", "name": "A. Papa"}, + {"authorId": "4584039", "name": "R. Hobbs"}, {"authorId": "48622732", "name": + "Ming Chen"}, {"authorId": "5729169", "name": "A. Lunardi"}, {"authorId": + "6294709", "name": "Christopher Ng"}, {"authorId": "4817196", "name": "Kaitlyn + A. Webster"}, {"authorId": "7505152", "name": "S. Signoretti"}, {"authorId": + "6213932", "name": "M. Loda"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "3547827", "name": "C. Nardella"}, {"authorId": "4102988", "name": + "J. Clohessy"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4499580", "name": "P. Pandolfi"}]}, {"paperId": "61f48f0d697a528e61079ac6c6009f4ca553fb47", + "externalIds": {"MAG": "2975233555", "DOI": "10.1016/j.ccell.2019.08.006", + "CorpusId": 203608586, "PubMed": "31564638"}, "corpusId": 203608586, "publicationVenue": + {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", "name": "Cancer Cell", "type": + "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/61f48f0d697a528e61079ac6c6009f4ca553fb47", + "title": "Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential + for Acquisition of Aggressive Traits and Metastatic Colonization.", "abstract": + null, "venue": "Cancer Cell", "year": 2019, "referenceCount": 88, "citationCount": + 39, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1535610819303745/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2019-10-01", "journal": {"name": "Cancer cell"}, "authors": + [{"authorId": "2087116099", "name": "Ana P Gomes"}, {"authorId": "3324022", + "name": "Didem Ilter"}, {"authorId": "121128193", "name": "V. Low"}, {"authorId": + "1887417083", "name": "A. Rosenzweig"}, {"authorId": "50530764", "name": "Zih-Jie + Shen"}, {"authorId": "50356549", "name": "Tanya Schild"}, {"authorId": "143749460", + "name": "M. Rivas"}, {"authorId": "48004390", "name": "E. Er"}, {"authorId": + "1381392860", "name": "Dylan R McNally"}, {"authorId": "5135907", "name": + "A. Mutvei"}, {"authorId": "1886508939", "name": "Julie Han"}, {"authorId": + "50051932", "name": "Yi-Hung Ou"}, {"authorId": "47026720", "name": "Paola + Cavaliere"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": + "37644389", "name": "Michal J. Nagiec"}, {"authorId": "3592587", "name": "Sejeong + Shin"}, {"authorId": "6168327", "name": "Sang-Oh Yoon"}, {"authorId": "4622316", + "name": "Noah Dephoure"}, {"authorId": "32314188", "name": "J. Massagu\u00e9"}, + {"authorId": "145150236", "name": "A. Melnick"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "143917917", "name": "J. Tyler"}, {"authorId": + "4037343", "name": "J. Blenis"}]}, {"paperId": "631e702c51d2c9b1a00a14fd00aa833d1df16ae2", + "externalIds": {"MAG": "2994107797", "DOI": "10.1016/j.celrep.2019.10.117", + "CorpusId": 208646787, "PubMed": "31801093"}, "corpusId": 208646787, "publicationVenue": + {"id": "a3fb5dc1-0d6e-4cd0-a720-8cb68cbf6486", "name": "Cell Reports", "type": + "journal", "alternate_names": ["Cell Rep"], "issn": "2211-1247", "url": "https://www.cell.com/cell-reports/home", + "alternate_urls": ["http://cellreports.cell.com/"]}, "url": "https://www.semanticscholar.org/paper/631e702c51d2c9b1a00a14fd00aa833d1df16ae2", + "title": "Quantitative In\u00a0Vivo Proteomics of Metformin Response in Liver + Reveals AMPK-Dependent and -Independent Signaling Networks.", "abstract": + null, "venue": "Cell Reports", "year": 2019, "referenceCount": 112, "citationCount": + 18, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S2211124719314500/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2019-12-01", "journal": {"volume": "29 10", "pages": "\n 3331-3348.e7\n ", + "name": "Cell reports"}, "authors": [{"authorId": "40353456", "name": "Benjamin + D. Stein"}, {"authorId": "3095517", "name": "Diego Calzolari"}, {"authorId": + "47088230", "name": "Kristina Hellberg"}, {"authorId": "49994864", "name": + "Ying S. Hu"}, {"authorId": "2112501583", "name": "Lin He"}, {"authorId": + "11153400", "name": "C. Hung"}, {"authorId": "7252928", "name": "E. Q. Toyama"}, + {"authorId": "4088273", "name": "Debbie S. Ross"}, {"authorId": "3960161", + "name": "B. Lillemeier"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "143613691", "name": "J. Yates"}, {"authorId": "4426388", "name": "R. Shaw"}]}, + {"paperId": "638dda37bbc4ca0c75e635a75dd696c6d678d76a", "externalIds": {"MAG": + "2989982593", "DOI": "10.1016/j.bbrc.2019.11.130", "CorpusId": 208536464, + "PubMed": "31787239"}, "corpusId": 208536464, "publicationVenue": {"id": "1a9c698b-7fe4-4444-b391-208b4b2326e2", + "name": "Biochemical and Biophysical Research Communications - BBRC", "type": + "journal", "alternate_names": ["Biochem Biophys Res Commun", "Biochemical + and Biophysical Research Communications", "Biochem Biophys Res Commun BBRC"], + "issn": "0006-291X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description", + "alternate_urls": ["http://www.idealibrary.com/links/toc/bbrc", "https://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/", + "http://www.sciencedirect.com/science/journal/0006291X"]}, "url": "https://www.semanticscholar.org/paper/638dda37bbc4ca0c75e635a75dd696c6d678d76a", + "title": "A covalent small molecule inhibitor of glutamate-oxaloacetate transaminase + 1 impairs pancreatic cancer growth.", "abstract": null, "venue": "Biochemical + and Biophysical Research Communications - BBRC", "year": 2019, "referenceCount": + 21, "citationCount": 24, "influentialCitationCount": 2, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2019-11-28", "journal": {"name": "Biochemical + and biophysical research communications"}, "authors": [{"authorId": "1439474141", + "name": "Tomohiro Yoshida"}, {"authorId": "2054062334", "name": "S. Yamasaki"}, + {"authorId": "2061019033", "name": "O. Kaneko"}, {"authorId": "47819651", + "name": "Naofumi Taoka"}, {"authorId": "48259254", "name": "Y. Tomimoto"}, + {"authorId": "10280879", "name": "I. Namatame"}, {"authorId": "1439712317", + "name": "Toshiko Yahata"}, {"authorId": "9541523", "name": "S. Kuromitsu"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4901222", "name": + "C. Lyssiotis"}]}, {"paperId": "6d532f6d1aa7ee773657e1e0b83c3950dc2a4c73", + "externalIds": {"MAG": "2982786587", "DOI": "10.1126/science.aaw9032", "CorpusId": + 207943491, "PubMed": "31699932"}, "corpusId": 207943491, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/6d532f6d1aa7ee773657e1e0b83c3950dc2a4c73", + "title": "Double PIK3CA mutations in cis increase oncogenicity and sensitivity + to PI3K\u03b1 inhibitors", "abstract": "Seeing double can be a good thing + Many human breast cancers harbor activating mutations in PIK3CA, the gene + coding for the catalytic subunit of phosphoinositide 3-kinase (PI3K). Clinical + trials are underway to evaluate the efficacy of PI3K inhibitors in cancer + patients. Vasan et al. found unexpectedly that a subset of breast cancers + harbor not one\u2014but two\u2014PIK3CA mutations, and the mutations occur + on the same allele (see the Perspective by Toker). In model systems, the double + mutations hyperactivate PI3K signaling and enhance tumor growth. Preliminary + analysis of clinical trial data suggests that breast cancers with double mutations + are more responsive to PI3K inhibitors than those with a single mutation. + PIK3CA mutational status could help identify the breast cancer patients most + likely to benefit from these drugs. Science, this issue p. 714; see also p. + 685 Activating mutations in PIK3CA are frequent in human breast cancer, and + phosphoinositide 3-kinase alpha (PI3K\u03b1) inhibitors have been approved + for therapy. To characterize determinants of sensitivity to these agents, + we analyzed PIK3CA-mutant cancer genomes and observed the presence of multiple + PIK3CA mutations in 12 to 15% of breast cancers and other tumor types, most + of which (95%) are double mutations. Double PIK3CA mutations are in cis on + the same allele and result in increased PI3K activity, enhanced downstream + signaling, increased cell proliferation, and tumor growth. The biochemical + mechanisms of dual mutations include increased disruption of p110\u03b1 binding + to the inhibitory subunit p85\u03b1, which relieves its catalytic inhibition, + and increased p110\u03b1 membrane lipid binding. Double PIK3CA mutations predict + increased sensitivity to PI3K\u03b1 inhibitors compared with single-hotspot + mutations. Some breast cancers harbor not one\u2014but two\u2014PIK3CA mutations, + and this enhances their response to certain drugs.", "venue": "Science", "year": + 2019, "referenceCount": 75, "citationCount": 133, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc7173400?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-11-07", "journal": + {"volume": "366", "pages": "714 - 723", "name": "Science"}, "authors": [{"authorId": + "35123724", "name": "N. Vasan"}, {"authorId": "3224289", "name": "P. Razavi"}, + {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": "2959236", + "name": "H. Shao"}, {"authorId": "49820132", "name": "H. Shah"}, {"authorId": + "49335811", "name": "Alesia Antoine"}, {"authorId": "3139198", "name": "Erik + Ladewig"}, {"authorId": "48892954", "name": "A. Gorelick"}, {"authorId": "144181325", + "name": "Ting-Yu Lin"}, {"authorId": "4733908", "name": "E. Toska"}, {"authorId": + "51290929", "name": "Guotai Xu"}, {"authorId": "150907238", "name": "Abiha + Kazmi"}, {"authorId": "2141904248", "name": "Matthew T. Chang"}, {"authorId": + "36898514", "name": "B. Taylor"}, {"authorId": "4713308", "name": "M. Dickler"}, + {"authorId": "47352468", "name": "K. Jhaveri"}, {"authorId": "6037809", "name": + "S. Chandarlapaty"}, {"authorId": "40620158", "name": "R. Rabad\u00e1n"}, + {"authorId": "145632788", "name": "E. Reznik"}, {"authorId": "2116670076", + "name": "M. Smith"}, {"authorId": "46517710", "name": "R. Sebra"}, {"authorId": + "5323777", "name": "F. Schimmoller"}, {"authorId": "2017652", "name": "T. + Wilson"}, {"authorId": "48530297", "name": "L. Friedman"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "8336319", "name": "M. Scaltriti"}, {"authorId": + "144806171", "name": "J. Baselga"}]}, {"paperId": "71ee96dbf928c1ff5bb600f55ea8afb2feb77e6c", + "externalIds": {"PubMedCentral": "6356657", "MAG": "2908494180", "DOI": "10.3390/cancers11010037", + "CorpusId": 58619743, "PubMed": "30609754"}, "corpusId": 58619743, "publicationVenue": + {"id": "d30776c0-e524-4f14-a524-871d0586862c", "name": "Cancers", "type": + "journal", "issn": "2072-6694", "url": "http://www.e-helvetica.nb.admin.ch/directAccess?callnumber=bel-154879", + "alternate_urls": ["http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:ch:bel-154879", + "https://www.mdpi.com/journal/cancers"]}, "url": "https://www.semanticscholar.org/paper/71ee96dbf928c1ff5bb600f55ea8afb2feb77e6c", + "title": "Rac-Mediated Macropinocytosis of Extracellular Protein Promotes + Glucose Independence in Non-Small Cell Lung Cancer", "abstract": "Cancer cells + can adapt to nutrient poor conditions by rewiring their metabolism and using + alternate fuel sources. Identifying these adaptive metabolic pathways may + provide novel targets for cancer therapy. Here, we identify a subset of non-small + cell lung cancer (NSCLC) cell lines that survive in the absence of glucose + by internalizing and metabolizing extracellular protein via macropinocytosis. + Macropinocytosis is increased in these glucose independent cells, and is regulated + by phosphoinositide 3-kinase (PI3K) activation of Rac-Pak signaling. Furthermore, + inhibition of Rac-dependent macropinocytosis blocks glucose-independent proliferation. + We find that degradation of internalized protein produces amino acids, including + alanine, which generates TCA cycle and glycolytic intermediates in the absence + of glucose. In this process, the conversion of alanine to pyruvate by alanine + transaminase 2 (ALT2) is critical for survival during glucose starvation. + Collectively, Rac driven macropinocytosis of extracellular protein is an adaptive + metabolic pathway used by a subset of lung cancers to survive states of glucose + deprivation, and may serve as a potential drug target for cancer therapy.", + "venue": "Cancers", "year": 2019, "referenceCount": 65, "citationCount": 31, + "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.mdpi.com/2072-6694/11/1/37/pdf?version=1546497470", "status": + null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2019-01-01", "journal": {"volume": "11", "name": "Cancers"}, + "authors": [{"authorId": "7331238", "name": "Cindy Hodakoski"}, {"authorId": + "48821307", "name": "B. Hopkins"}, {"authorId": "49288368", "name": "Guoan + Zhang"}, {"authorId": "41096321", "name": "Taojunfeng Su"}, {"authorId": "2113278909", + "name": "Zhe Cheng"}, {"authorId": "29869805", "name": "R. Morris"}, {"authorId": + "4097554", "name": "K. Rhee"}, {"authorId": "145524334", "name": "M. Goncalves"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "74eaf5f163eac54fd3d4162a728d480381508c66", + "externalIds": {"MAG": "2974449317", "PubMedCentral": "6757060", "DOI": "10.1038/s41523-019-0126-6", + "CorpusId": 202718135, "PubMed": "31552290"}, "corpusId": 202718135, "publicationVenue": + {"id": "67d103e1-4f88-438e-9a44-831e2b35695b", "name": "npj Breast Cancer", + "issn": "2374-4677", "url": "https://www.nature.com/npjbcancer/"}, "url": + "https://www.semanticscholar.org/paper/74eaf5f163eac54fd3d4162a728d480381508c66", + "title": "PIK3CA and MAP3K1 alterations imply luminal A status and are associated + with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in + ER+ metastatic breast cancer", "abstract": null, "venue": "npj Breast Cancer", + "year": 2019, "referenceCount": 36, "citationCount": 15, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/s41523-019-0126-6.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2019-09-23", "journal": {"volume": "5", "name": "NPJ Breast + Cancer"}, "authors": [{"authorId": "36673810", "name": "Mellissa J. Nixon"}, + {"authorId": "40940752", "name": "L. Formisano"}, {"authorId": "2346140", + "name": "I. Mayer"}, {"authorId": "144820856", "name": "M. V. Estrada"}, {"authorId": + "1400994437", "name": "P. Gonzalez-Ericsson"}, {"authorId": "4327978", "name": + "S. Isakoff"}, {"authorId": "1398378390", "name": "A. Forero-Torres"}, {"authorId": + "3738649", "name": "H. Won"}, {"authorId": "46945931", "name": "M. Sanders"}, + {"authorId": "2344124", "name": "D. Solit"}, {"authorId": "33727638", "name": + "M. Berger"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2369378", "name": "E. Winer"}, {"authorId": "2057460", "name": "C. Arteaga"}, + {"authorId": "66935619", "name": "J. Balko"}]}, {"paperId": "753f266db29ae0d2f8f33314c03b094b8e9913a1", + "externalIds": {"PubMedCentral": "6612080", "MAG": "2955973158", "DOI": "10.1186/s13058-019-1154-8", + "CorpusId": 195804282, "PubMed": "31277699"}, "corpusId": 195804282, "publicationVenue": + {"id": "1290af6c-c79c-4253-8957-8db4a6069766", "name": "Breast Cancer Research", + "type": "journal", "alternate_names": ["Breast Cancer Res"], "issn": "1465-5411", + "url": "http://breast-cancer-research.com/"}, "url": "https://www.semanticscholar.org/paper/753f266db29ae0d2f8f33314c03b094b8e9913a1", + "title": "Phase II trial of AKT inhibitor MK-2206 in patients with advanced + breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN + mutation", "abstract": null, "venue": "Breast Cancer Research", "year": 2019, + "referenceCount": 32, "citationCount": 106, "influentialCitationCount": 2, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-07-05", "journal": + {"volume": "21", "name": "Breast Cancer Research : BCR"}, "authors": [{"authorId": + "145712222", "name": "Y. Xing"}, {"authorId": "35141217", "name": "N. Lin"}, + {"authorId": "144226560", "name": "M. Maurer"}, {"authorId": "49177752", "name": + "Huiqin Chen"}, {"authorId": "5314564", "name": "A. Mahvash"}, {"authorId": + "2676017", "name": "A. Sahin"}, {"authorId": "6046757", "name": "A. Akcakanat"}, + {"authorId": "2111151410", "name": "Yisheng Li"}, {"authorId": "2186029", + "name": "V. Abramson"}, {"authorId": "3219926", "name": "J. Litton"}, {"authorId": + "1390005035", "name": "M. Ch\u00e1vez-MacGregor"}, {"authorId": "116205756", + "name": "V. Valero"}, {"authorId": "1422512895", "name": "S. Piha-Paul"}, + {"authorId": "2788997", "name": "D. Hong"}, {"authorId": "145302986", "name": + "K. Do"}, {"authorId": "5285731", "name": "E. Tarco"}, {"authorId": "1417281255", + "name": "Dianna Riall"}, {"authorId": "2927324", "name": "A. Eterovic"}, {"authorId": + "31554501", "name": "G. Wulf"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2241330", "name": "G. Mills"}, {"authorId": "39667616", "name": + "L. Doyle"}, {"authorId": "2369378", "name": "E. Winer"}, {"authorId": "4172107", + "name": "G. Hortobagyi"}, {"authorId": "1398194828", "name": "A. Gonz\u00e1lez-Angulo"}, + {"authorId": "1397965147", "name": "F. Meric-Bernstam"}]}, {"paperId": "7c8465ae4bb9c9628afd90cabf5555d91e7d43aa", + "externalIds": {"MAG": "2921937041", "DOI": "10.1158/1538-7445.SABCS18-TS2-1", + "CorpusId": 87124605}, "corpusId": 87124605, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/7c8465ae4bb9c9628afd90cabf5555d91e7d43aa", + "title": "Abstract TS2-1: The complexity of targeting PI3K for cancer therapy", + "abstract": "Phosphoinositide 3-Kinase (PI3K) is activated by insulin and + other growth factors to mediate cell growth. The PI3K enzyme encoded by the + PIK3CA gene is one of the most frequently mutated oncogenes in human cancer. + This same enzyme mediates insulin responses in liver, muscle, fat and other + tissues. The most common mutations in this gene enhance the ability of PI3K + to be activated by insulin. Since breast cancers typically express relatively + high levels of the insulin receptor, high serum insulin levels are likely + to enhance activation of PI3K in breast cancers. PI3K inhibitors that target + PIK3CA have the expected physiological effect of raising serum glucose and + insulin levels and the elevated insulin is likely to compromise the effectiveness + of therapy. Data will be presented showing that in mouse models of human breast + cancers and other cancers, dietary interventions and pharmaceutical interventions + that limit elevation of serum insulin during PI3K therapy improve responses + to PI3K inhibitors. Citation Format: Cantley L. The complexity of targeting + PI3K for cancer therapy [abstract]. In: Proceedings of the 2018 San Antonio + Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): + AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS2-1.", "venue": "Invited Speaker + Abstracts", "year": 2019, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2019-02-15", "journal": {"name": + "Invited Speaker Abstracts"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "8133bedd80d6d8bfd87f5a07f4fd578cca72603c", "externalIds": + {"MAG": "2985502989", "DOI": "10.1002/ijc.32783", "CorpusId": 207939132, "PubMed": + "31714586"}, "corpusId": 207939132, "publicationVenue": {"id": "a71ca720-16ee-4930-9112-7e88084f2312", + "name": "International Journal of Cancer", "type": "journal", "alternate_names": + ["Int J Cancer"], "issn": "0020-7136", "url": "http://www.interscience.wiley.com/jpages/0020-7136/", + "alternate_urls": ["https://onlinelibrary.wiley.com/journal/10970215", "http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0215"]}, + "url": "https://www.semanticscholar.org/paper/8133bedd80d6d8bfd87f5a07f4fd578cca72603c", + "title": "Phase II, 2\u2010stage, 2\u2010arm, PIK3CA mutation stratified trial + of MK\u20102206 in recurrent endometrial cancer", "abstract": "Endometrial + cancers have high rates of phosphoinositide 3\u2010kinase (PI3K) pathway alterations. + MK\u20102206 is an allosteric inhibitor of AKT, an effector kinase of PI3K + signals. We hypothesized patients with tumors harboring PIK3CA mutations would + be more likely to benefit from MK\u20102206 than those without PIK3CA mutation. + A Phase II study was performed in patients with recurrent endometrial cancer; + all histologies except carcinosarcoma were eligible. Up to two prior chemotherapy + lines were permitted, excluding prior treatment with PI3K pathway inhibitors. + The first 18 patients were treated with MK\u20102206 200\u2009mg weekly. Due + to unacceptable toxicity, dose was reduced to 135\u2009mg. Co\u2010primary + endpoints were objective response rate (ORR) and progression\u2010free survival + at 6 months (6moPFS). Thirty\u2010seven patients were enrolled (one ineligible). + By somatic PIK3CA mutation analysis, nine patients were mutant (MT) [one with + partial response (PR)/6moPFS, two with 6moPFS]. Twenty\u2010seven patients + were wild\u2010type (WT) (one PR and four 6moPFS). Most common toxicities + were rash (44%), fatigue (41%), nausea (42%) and hyperglycemia (31%). Grade + 3 and 4 toxicities occurred in 25 and 17% of patients, respectively. Exploratory + analysis found serous histology had greater 6moPFS as compared to all other + histologies (5/8 vs. 2/28, p =\u20090.003). PTEN expression was associated + with median time to progression (p =\u20090.04). No other significant associations + with PI3K pathway alterations were identified. There is limited single agent + activity of MK\u20102206 in PIK3CA MT and PIK3CA WT endometrial cancer populations. + Activity was detected in patients with serous histology and due to their poor + outcomes warrants further study (NCT01307631).", "venue": "International Journal + of Cancer", "year": 2019, "referenceCount": 32, "citationCount": 23, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-11-12", "journal": + {"volume": "147", "name": "International Journal of Cancer"}, "authors": [{"authorId": + "6324437", "name": "A. Myers"}, {"authorId": "49610180", "name": "P. Konstantinopoulos"}, + {"authorId": "143997654", "name": "W. Barry"}, {"authorId": "4146119", "name": + "W. Luo"}, {"authorId": "6416382", "name": "R. Broaddus"}, {"authorId": "3553012", + "name": "V. Makker"}, {"authorId": "5340828", "name": "R. Drapkin"}, {"authorId": + "2108419806", "name": "Joyce F. Liu"}, {"authorId": "2523814", "name": "A. + Doyle"}, {"authorId": "8523393", "name": "N. Horowitz"}, {"authorId": "1397965147", + "name": "F. Meric-Bernstam"}, {"authorId": "2167106", "name": "M. Birrer"}, + {"authorId": "6128162", "name": "C. Aghajanian"}, {"authorId": "3124983", + "name": "R. Coleman"}, {"authorId": "2241330", "name": "G. Mills"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6927295", "name": "U. Matulonis"}, + {"authorId": "2974900", "name": "S. Westin"}]}, {"paperId": "9929df74a7789e0bf73699a7ceb5cd2b0bf0b1a1", + "externalIds": {"MAG": "2921326512", "PubMedCentral": "6414673", "DOI": "10.1038/s41598-019-40950-7", + "CorpusId": 75138869, "PubMed": "30862944"}, "corpusId": 75138869, "publicationVenue": + {"id": "f99f77b7-b1b6-44d3-984a-f288e9884b9b", "name": "Scientific Reports", + "type": "journal", "alternate_names": ["Sci Rep"], "issn": "2045-2322", "url": + "http://www.nature.com/srep/", "alternate_urls": ["http://www.nature.com/srep/index.html"]}, + "url": "https://www.semanticscholar.org/paper/9929df74a7789e0bf73699a7ceb5cd2b0bf0b1a1", + "title": "Regulation of folate and methionine metabolism by multisite phosphorylation + of human methylenetetrahydrofolate reductase", "abstract": null, "venue": + "Scientific Reports", "year": 2019, "referenceCount": 28, "citationCount": + 15, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/s41598-019-40950-7.pdf", "status": + null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2019-03-12", "journal": {"volume": "9", "name": "Scientific Reports"}, "authors": + [{"authorId": "1723564", "name": "Yuxiang Zheng"}, {"authorId": "14390729", + "name": "Shivan Ramsamooj"}, {"authorId": "2146274806", "name": "Qian Li"}, + {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": "5247030", + "name": "Tomer M. Yaron"}, {"authorId": "82239758", "name": "Klaus Sharra"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "bc4aeb00e18e86296ff75b6bd1726556b269ce03", + "externalIds": {"MAG": "2922809418", "DOI": "10.1126/science.aat8515", "CorpusId": + 85447337, "PubMed": "30898933"}, "corpusId": 85447337, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/bc4aeb00e18e86296ff75b6bd1726556b269ce03", + "title": "High-fructose corn syrup enhances intestinal tumor growth in mice", + "abstract": "A sweetener''s not-so-sweet effects Obesity increases an individual''s + risk of developing many types of cancer, including colorectal cancer. One + of the factors driving the rise in obesity rates is thought to be the use + of high-fructose corn syrup (HFCS) as a sweetener in soft drinks. Goncalves + et al. found that ingestion of HFCS promotes the growth of intestinal cancer + even in the absence of obesity in mouse tumor models. An enzyme in tumors + (ketohexokinase) converts fructose to fructose-1-phosphate, which alters tumor + cell metabolism and leads to enhanced cell growth. Whether a similar process + occurs in humans remains to be seen. Science, this issue p. 1345 Eating high-fructose + corn syrup enhances growth of intestinal cancer in mice by altering tumor + cell metabolism. Excessive consumption of beverages sweetened with high-fructose + corn syrup (HFCS) is associated with obesity and with an increased risk of + colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. + We investigated the effects of daily oral administration of HFCS in adenomatous + polyposis coli (APC) mutant mice, which are predisposed to develop intestinal + tumors. The HFCS-treated mice showed a substantial increase in tumor size + and tumor grade in the absence of obesity and metabolic syndrome. HFCS increased + the concentrations of fructose and glucose in the intestinal lumen and serum, + respectively, and the tumors transported both sugars. Within the tumors, fructose + was converted to fructose-1-phosphate, leading to activation of glycolysis + and increased synthesis of fatty acids that support tumor growth. These mouse + studies support the hypothesis that the combination of dietary glucose and + fructose, even at a moderate dose, can enhance tumorigenesis.", "venue": "Science", + "year": 2019, "referenceCount": 56, "citationCount": 165, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc6487857?pdf=render", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2019-03-22", "journal": {"volume": "363", "pages": "1345 + - 1349", "name": "Science"}, "authors": [{"authorId": "145524334", "name": + "M. Goncalves"}, {"authorId": "7434113", "name": "Changyuan Lu"}, {"authorId": + "88672565", "name": "Jordan Tutnauer"}, {"authorId": "32250589", "name": "T. + Hartman"}, {"authorId": "4151944", "name": "Seo-Kyoung Hwang"}, {"authorId": + "47107919", "name": "Charles J Murphy"}, {"authorId": "34187590", "name": + "C. Pauli"}, {"authorId": "29869805", "name": "R. Morris"}, {"authorId": "2110994237", + "name": "Samuel R Taylor"}, {"authorId": "7881810", "name": "Kaitlyn Bosch"}, + {"authorId": "88708777", "name": "Sukjin Yang"}, {"authorId": "2115641579", + "name": "Yumei Wang"}, {"authorId": "88611660", "name": "Justin Van Riper"}, + {"authorId": "6057803", "name": "H. C. Lekaye"}, {"authorId": "145864068", + "name": "J. Roper"}, {"authorId": "2152652898", "name": "Young Kim"}, {"authorId": + "2109625387", "name": "Qiuying Chen"}, {"authorId": "5769141", "name": "S. + Gross"}, {"authorId": "4097554", "name": "K. Rhee"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "40164091", "name": "Jihye Yun"}]}, {"paperId": + "c11be0f675f6355e027f1bfb270824da7a5312f3", "externalIds": {"DOI": "10.1158/1078-0432.CCR-18-4269", + "CorpusId": 73496753, "PubMed": "30770491"}, "corpusId": 73496753, "publicationVenue": + {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", "name": "Clinical Cancer Research", + "type": "journal", "alternate_names": ["Clin Cancer Res"], "issn": "1078-0432", + "url": "https://clincancerres.aacrjournals.org/", "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/c11be0f675f6355e027f1bfb270824da7a5312f3", + "title": "Correction: PIK3CA C2 Domain Deletions Hyperactivate Phosphoinositide + 3-kinase (PI3K), Generate Oncogene Dependence, and Are Exquisitely Sensitive + to PI3K\u03b1 Inhibitors", "abstract": null, "venue": "Clinical Cancer Research", + "year": 2019, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2019-02-15", "journal": {"volume": "25", "pages": "1432 + - 1432", "name": "Clinical Cancer Research"}, "authors": [{"authorId": "5404128", + "name": "Sarah Croessmann"}, {"authorId": "6251014", "name": "J. Sheehan"}, + {"authorId": "46542827", "name": "Kyung-Min Lee"}, {"authorId": "3381467", + "name": "Gregory Sliwoski"}, {"authorId": "50774890", "name": "Ji\u00e9 He"}, + {"authorId": "39540895", "name": "R. Nagy"}, {"authorId": "82059310", "name": + "David A. Riddle"}, {"authorId": "2346140", "name": "I. Mayer"}, {"authorId": + "66935619", "name": "J. Balko"}, {"authorId": "3484938", "name": "R. Lanman"}, + {"authorId": "2134288", "name": "V. Miller"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "1754226", "name": "J. Meiler"}, {"authorId": + "2057460", "name": "C. Arteaga"}]}, {"paperId": "cb54ae094afe53c4b8ef7acf71cfe64c9068aab5", + "externalIds": {"MAG": "3091952721", "DOI": "10.1186/s13058-019-1154-8", "CorpusId": + 225157186}, "corpusId": 225157186, "publicationVenue": {"id": "1290af6c-c79c-4253-8957-8db4a6069766", + "name": "Breast Cancer Research", "type": "journal", "alternate_names": ["Breast + Cancer Res"], "issn": "1465-5411", "url": "http://breast-cancer-research.com/"}, + "url": "https://www.semanticscholar.org/paper/cb54ae094afe53c4b8ef7acf71cfe64c9068aab5", + "title": "Phase II trial of AKT inhibitor MK-2206 in patients with advanced + breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN + mutation", "abstract": null, "venue": "Breast Cancer Research", "year": 2019, + "referenceCount": 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Medicine", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2019-07-05", "journal": {"volume": + "21", "name": "Breast Cancer Research"}, "authors": [{"authorId": "145712222", + "name": "Y. Xing"}, {"authorId": "35141217", "name": "N. Lin"}, {"authorId": + "144226560", "name": "M. Maurer"}, {"authorId": "49177752", "name": "Huiqin + Chen"}, {"authorId": "5314564", "name": "A. Mahvash"}, {"authorId": "2676017", + "name": "A. Sahin"}, {"authorId": "6046757", "name": "A. Akcakanat"}, {"authorId": + "2111151410", "name": "Yisheng Li"}, {"authorId": "2186029", "name": "V. Abramson"}, + {"authorId": "3219926", "name": "J. Litton"}, {"authorId": "1390005035", "name": + "M. Ch\u00e1vez-MacGregor"}, {"authorId": "116205756", "name": "V. Valero"}, + {"authorId": "1422512895", "name": "S. Piha-Paul"}, {"authorId": "2788997", + "name": "D. Hong"}, {"authorId": "145302986", "name": "K. Do"}, {"authorId": + "5285731", "name": "E. Tarco"}, {"authorId": "1417281255", "name": "Dianna + Riall"}, {"authorId": "2927324", "name": "A. Eterovic"}, {"authorId": "31554501", + "name": "G. Wulf"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "39667616", "name": "L. Doyle"}, + {"authorId": "2369378", "name": "E. Winer"}, {"authorId": "4172107", "name": + "G. Hortobagyi"}, {"authorId": "1398194828", "name": "A. Gonz\u00e1lez-Angulo"}, + {"authorId": "1397965147", "name": "F. Meric-Bernstam"}]}, {"paperId": "e0f844bdbb33fad4a3485cecb85af76b7ab22f36", + "externalIds": {"MAG": "2938641131", "DOI": "10.1038/s41568-019-0135-7", "CorpusId": + 106409019, "PubMed": "30967651"}, "corpusId": 106409019, "publicationVenue": + {"id": "db36cc4c-07df-41a8-9169-9ace7e520923", "name": "Nature Reviews. Cancer", + "type": "journal", "alternate_names": ["Nature Reviews Cancer", "Nat Rev Cancer"], + "issn": "1474-175X", "url": "https://www.nature.com/nrc/", "alternate_urls": + ["http://www.nature.com/nrc/index.html"]}, "url": "https://www.semanticscholar.org/paper/e0f844bdbb33fad4a3485cecb85af76b7ab22f36", + "title": "Targeting cancer vulnerabilities with high-dose vitamin C", "abstract": + null, "venue": "Nature Reviews. Cancer", "year": 2019, "referenceCount": 148, + "citationCount": 176, "influentialCitationCount": 8, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc6526932?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2019-05-01", "journal": {"volume": + "19", "pages": "271-282", "name": "Nature Reviews Cancer"}, "authors": [{"authorId": + "5891999", "name": "B. Ngo"}, {"authorId": "88611660", "name": "Justin Van + Riper"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "40164091", + "name": "Jihye Yun"}]}, {"paperId": "e47452e6e2f9ba30da769cbdcb44fb917ec6796a", + "externalIds": {"MAG": "2921991537", "DOI": "10.1016/S1470-2045(18)30905-7", + "CorpusId": 81983081, "PubMed": "30880072"}, "corpusId": 81983081, "publicationVenue": + {"id": "4bb62465-2dd3-4eca-923f-4649b9dea666", "name": "The Lancet Oncology", + "type": "journal", "alternate_names": ["Lancet Oncol", "Lancet Oncology"], + "issn": "1470-2045", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/621215/description#description", + "alternate_urls": ["https://www.sciencedirect.com/journal/the-lancet-oncology/", + "http://www.sciencedirect.com/science/journal/14702045", "http://www.thelancet.com/journals/lanonc", + "http://oncology.thelancet.com/journal"]}, "url": "https://www.semanticscholar.org/paper/e47452e6e2f9ba30da769cbdcb44fb917ec6796a", + "title": "Olaparib and \u03b1-specific PI3K inhibitor alpelisib for patients + with epithelial ovarian cancer: a dose-escalation and dose-expansion phase + 1b trial.", "abstract": null, "venue": "The Lancet Oncology", "year": 2019, + "referenceCount": 33, "citationCount": 129, "influentialCitationCount": 3, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc7025391?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2019-04-01", "journal": + {"volume": "20 4", "pages": "\n 570-580\n ", "name": "The + Lancet. Oncology"}, "authors": [{"authorId": "49610180", "name": "P. Konstantinopoulos"}, + {"authorId": "143997654", "name": "W. Barry"}, {"authorId": "2167106", "name": + "M. Birrer"}, {"authorId": "2974900", "name": "S. Westin"}, {"authorId": "5372086", + "name": "K. Cadoo"}, {"authorId": "2014583", "name": "G. Shapiro"}, {"authorId": + "3349811", "name": "E. Mayer"}, {"authorId": "1388881568", "name": "R. O\u2019Cearbhaill"}, + {"authorId": "3124983", "name": "R. Coleman"}, {"authorId": "4604359", "name": + "B. Kochupurakkal"}, {"authorId": "122974814", "name": "C. Whalen"}, {"authorId": + "49142258", "name": "J. Curtis"}, {"authorId": "7862178", "name": "S. Farooq"}, + {"authorId": "4146119", "name": "W. Luo"}, {"authorId": "27883005", "name": + "J. Eismann"}, {"authorId": "31331831", "name": "M. Buss"}, {"authorId": "6128162", + "name": "C. Aghajanian"}, {"authorId": "2241330", "name": "G. Mills"}, {"authorId": + "32453098", "name": "S. Palakurthi"}, {"authorId": "3588774", "name": "P. + Kirschmeier"}, {"authorId": "2108419806", "name": "Joyce F. Liu"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144100151", "name": "S. Kaufmann"}, + {"authorId": "3733822", "name": "E. Swisher"}, {"authorId": "1396108662", + "name": "A. D\u2019Andrea"}, {"authorId": "2369378", "name": "E. Winer"}, + {"authorId": "31554501", "name": "G. Wulf"}, {"authorId": "6927295", "name": + "U. Matulonis"}]}, {"paperId": "f03f57a566a0058b551e4bb9f2aa20f2bf9ea965", + "externalIds": {"MAG": "2955344115", "DOI": "10.1016/j.bmcl.2019.07.011", + "CorpusId": 198133583, "PubMed": "31327531"}, "corpusId": 198133583, "publicationVenue": + {"id": "56cde9e1-007e-4232-b5ea-ac20f55c39e8", "name": "Bioorganic & Medicinal + Chemistry Letters", "type": "journal", "alternate_names": ["Bioorganic Med + Chem Lett"], "issn": "0960-894X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/972/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/0960894X", + "https://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry"]}, + "url": "https://www.semanticscholar.org/paper/f03f57a566a0058b551e4bb9f2aa20f2bf9ea965", + "title": "Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole + amides abrogates de novo serine synthesis in cancer cells.", "abstract": null, + "venue": "Bioorganic & Medicinal Chemistry Letters", "year": 2019, "referenceCount": + 30, "citationCount": 33, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2019-09-01", "journal": {"name": "Bioorganic + & medicinal chemistry letters"}, "authors": [{"authorId": "6424987", "name": + "Edouard Mullarky"}, {"authorId": "49394520", "name": "Jiayi Xu"}, {"authorId": + "13966444", "name": "A. Robin"}, {"authorId": "1969533", "name": "D. Huggins"}, + {"authorId": "47923264", "name": "A. Jennings"}, {"authorId": "15227811", + "name": "N. Noguchi"}, {"authorId": "13348478", "name": "A. Olland"}, {"authorId": + "46409661", "name": "D. Lakshminarasimhan"}, {"authorId": "2111174044", "name": + "Michael Miller"}, {"authorId": "46586540", "name": "D. Tomita"}, {"authorId": + "4944172", "name": "M. Michino"}, {"authorId": "41096321", "name": "Taojunfeng + Su"}, {"authorId": "49288368", "name": "Guoan Zhang"}, {"authorId": "6453464", + "name": "A. Stamford"}, {"authorId": "3284914", "name": "P. Meinke"}, {"authorId": + "4524238", "name": "S. Kargman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "ff97d958779a9e6edbd5c4bb0a984aa2cf61705f", "externalIds": {"MAG": + "2897987907", "DOI": "10.1016/j.jaci.2018.10.005", "CorpusId": 53020063, "PubMed": + "30336224"}, "corpusId": 53020063, "publicationVenue": {"id": "db8b4563-d667-494e-b2e2-bc65c4faba39", + "name": "Journal of Allergy and Clinical Immunology", "type": "journal", "alternate_names": + ["The Journal of Allergy and Clinical Immunology", "J Allergy Clin Immunol"], + "issn": "0091-6749", "url": "http://www.sciencedirect.com/science/journal/00916749", + "alternate_urls": ["http://www.jacionline.org/", "https://www.jacionline.org/"]}, + "url": "https://www.semanticscholar.org/paper/ff97d958779a9e6edbd5c4bb0a984aa2cf61705f", + "title": "Human primary immunodeficiency caused by expression of a kinase-dead + p110\u03b4 mutant.", "abstract": null, "venue": "Journal of Allergy and Clinical + Immunology", "year": 2019, "referenceCount": 10, "citationCount": 21, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jacionline.org/article/S0091674918314404/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2019-02-01", "journal": {"volume": + "143 2", "pages": "\n 797-799.e2\n ", "name": "The Journal + of allergy and clinical immunology"}, "authors": [{"authorId": "2116349094", + "name": "S. Cohen"}, {"authorId": "4303471", "name": "Wayne Bainter"}, {"authorId": + "145916288", "name": "Jared L. Johnson"}, {"authorId": "144181325", "name": + "Ting-Yu Lin"}, {"authorId": "40497062", "name": "Jenny C. Y. Wong"}, {"authorId": + "144318077", "name": "Jacqueline G. Wallace"}, {"authorId": "39780100", "name": + "Jennifer Jones"}, {"authorId": "3523481", "name": "S. Qureshi"}, {"authorId": + "144229106", "name": "F. Mir"}, {"authorId": "5522123", "name": "F. Qamar"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "47142358", "name": + "R. Geha"}, {"authorId": "144585371", "name": "J. Chou"}]}, {"paperId": "0c7f4d6945cbe59eb8bd1aff8be1376daadc137f", + "externalIds": {"MAG": "2902258211", "DOI": "10.1016/j.cell.2018.09.041", + "CorpusId": 54114483, "PubMed": "30500537"}, "corpusId": 54114483, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/0c7f4d6945cbe59eb8bd1aff8be1376daadc137f", + "title": "Mitochondrial One-Carbon Pathway Supports Cytosolic Folate Integrity + in Cancer Cells", "abstract": null, "venue": "Cell", "year": 2018, "referenceCount": + 74, "citationCount": 59, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S0092867418312534/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2018-11-01", "journal": {"volume": + "175", "pages": "1546-1560.e17", "name": "Cell"}, "authors": [{"authorId": + "1723564", "name": "Yuxiang Zheng"}, {"authorId": "144181325", "name": "Ting-Yu + Lin"}, {"authorId": "2123198", "name": "Gina Lee"}, {"authorId": "4422893", + "name": "M. Paddock"}, {"authorId": "5546246", "name": "Jessica Momb"}, {"authorId": + "46504255", "name": "Zhe Cheng"}, {"authorId": "2146274806", "name": "Qian + Li"}, {"authorId": "6841228", "name": "D. Fei"}, {"authorId": "40353456", + "name": "Benjamin D. Stein"}, {"authorId": "14390729", "name": "Shivan Ramsamooj"}, + {"authorId": "49288368", "name": "Guoan Zhang"}, {"authorId": "4037343", "name": + "J. Blenis"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "0d9ae101ee3cb4a46076eeda1298750a7b0aeb0c", "externalIds": {"MAG": "2901352207", + "DOI": "10.1182/BLOOD-2018-99-118355", "CorpusId": 186627443}, "corpusId": + 186627443, "publicationVenue": {"id": "9b6db04a-2990-4cf9-a14c-01d47636ee53", + "name": "Blood", "type": "journal", "issn": "0006-4971", "url": "http://www.bloodjournal.org/"}, + "url": "https://www.semanticscholar.org/paper/0d9ae101ee3cb4a46076eeda1298750a7b0aeb0c", + "title": "Development of Inhibitors of PIP4K2 As a Treatment for Patients + with Hematologic Malignancies", "abstract": "\n Phosphoinositide signaling + is central to many cellular processes including the cell survival pathway + known as autophagy. While there is evidence that autophagy can suppress tumorigenesis + under certain circumstances, there is increasingly abundant evidence that + autophagy promotes tumorigenesis and tumor cell survival in solid tumors and + hematologic malignancies.\n Autophagy is a complex process that has evolved + to promote survival of cells under a variety of stress or nutrient starvation + conditions. There are a multitude of molecules and structures involved in + initiating, promoting, and resolving the autophagy process. It is known that + PI5P is an important component for the resolution of autophagy. PIP4K2\u03b1,\u03b2,\u03b3 + are a family of lipid kinases that convert PI5P to PI(4,5)P2. These enzymes + have recently been shown to be critical for the fusion of autophagosomes with + lysosomes. This known activity, coupled with the observation that PIP4K2 activity + is essential for the survival and leukemia initiating potential of human and + mouse acute myeloid leukemia (AML) cells, suggest that the PIP4K2 family of + enzymes may be a promising target for a new class of therapeutics for the + treatment of hematologic malignancies.\n We have investigated the role of + PIP4K2 enzymes in supporting the survival of cancer cells by developing potent + and selective inhibitors of PIP4K2 enzymatic activity. A screen of human cancer + cell lines show that potent and selective inhibitors of PIP4K2 are effective + at inhibiting growth of a variety of hematologic cancers including leukemia- + and lymphoma-derived lines. In vivo studies demonstrate that these inhibitors + induce rapid regression of an AML tumor (MOLM-16) in a mouse xenograft model. + These studies show a dose-dependent control of tumor growth with sustained + regression of tumor volume with QD oral dosing of a prototype molecule. Body + weights of the mice were stable over the course of the study suggesting that + the molecule is well tolerated in this dosing protocol.\n A preliminary toxicity + study in rats has not revealed any identifiable toxicity at doses up to 100 + mg/Kg given QD/PO for 14 days. Additional in vitro safety studies suggest + minimal safety concerns due to off-target activity.\n Exploration of the structure + activity relationship of PIP4K2 inhibitors, using fragment and structure-based + drug discovery, has led to highly potent and selective molecules with exceptional + drug-like properties. A clinical development candidate has been selected and + that candidate is currently in the late stages of preclinical studies preceding + anticipated clinical entry in early 2019.\n \n \n McElligott: Petra Pharma: + Employment, Equity Ownership. Kesicki:Petra Pharma: Employment, Equity Ownership. + Karukarichi:Petra Pharma: Employment, Equity Ownership. Shim:Petra Pharma: + Employment, Equity Ownership. Wang:Petra Pharma: Employment, Equity Ownership. + Yu:Petra Pharma: Employment, Equity Ownership. Zolfaghari:Petra Pharma: Employment, + Equity Ownership. Linstrom:Sprint Bioscience: Employment, Equity Ownership. + Persson:Sprint Bioscience: Employment, Equity Ownership. Hoglund:Sprint Bioscience: + Employment, Equity Ownership. Ericsson:Sprint Bioscience: Employment, Equity + Ownership. Tr\u00e9saugues:Sprint Bioscience: Employment, Equity Ownership. + Livendahl:Sprint Bioscience: Employment, Equity Ownership. Santangelo:Sprint + Bioscience: Employment, Equity Ownership. Viklund:Sprint Bioscience: Employment, + Equity Ownership. Pettersson:Sprint Bioscience: Employment, Equity Ownership. + W\u00e4hling:Sprint Bioscience: Employment, Equity Ownership. Forsblom:Sprint + Bioscience: Employment, Equity Ownership. Karlsson:Sprint Bioscience: Employment, + Equity Ownership. Ginman:Sprint Bioscience: Employment, Equity Ownership. + Braga:Sprint Bioscience: Employment, Equity Ownership. Henley:Sprint Bioscience: + Employment, Equity Ownership. Talagas:Sprint Bioscience: Employment, Equity + Ownership. Rahm:Sprint Bioscience: Employment, Equity Ownership. Johansson:Sprint + Bioscience: Employment, Equity Ownership. Martinsson:Sprint Bioscience: Employment, + Equity Ownership. Andersson:Sprint Bioscience: Employment, Equity Ownership. + Cantley:Petra Pharma: Equity Ownership.\n", "venue": "Blood", "year": 2018, + "referenceCount": 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2018-11-29", + "journal": {"name": "Blood"}, "authors": [{"authorId": "8046282", "name": + "D. McElligott"}, {"authorId": "4354461", "name": "E. Kesicki"}, {"authorId": + "1435233809", "name": "Kannan Karukarichi"}, {"authorId": "13574443", "name": + "Hyeseok Shim"}, {"authorId": "2151036825", "name": "Rui Wang"}, {"authorId": + "145955019", "name": "A. Yu"}, {"authorId": "1435230665", "name": "Parisa + Zolfaghari"}, {"authorId": "150151571", "name": "J. Linstrom"}, {"authorId": + "2196197544", "name": "Persson Lars Boukharta"}, {"authorId": "35742521", + "name": "A. H\u00f6glund"}, {"authorId": "87585264", "name": "U. Ericsson"}, + {"authorId": "50076917", "name": "L. Tr\u00e9saugues"}, {"authorId": "2196193854", + "name": "Livendahl Madeleine"}, {"authorId": "2083195145", "name": "E. Santangelo"}, + {"authorId": "2409612", "name": "J. Viklund"}, {"authorId": "117559764", "name": + "M. Pettersson"}, {"authorId": "13984371", "name": "H. W\u00e4hling"}, {"authorId": + "15701764", "name": "Rickard Forsblom"}, {"authorId": "35383870", "name": + "F. Karlsson"}, {"authorId": "48235855", "name": "T. Ginman"}, {"authorId": + "89679374", "name": "Tiago Braga"}, {"authorId": "33023819", "name": "A. Henley"}, + {"authorId": "50405647", "name": "A. Talagas"}, {"authorId": "7782461", "name": + "F. Rahm"}, {"authorId": "2022372", "name": "T. Johansson"}, {"authorId": + "38766462", "name": "J. Martinsson"}, {"authorId": "144725033", "name": "M. + Andersson"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "191c5d5e815a92a5073304ffd393c1582dd58b98", "externalIds": {"MAG": "2905656919", + "PubMedCentral": "6363433", "DOI": "10.1084/jem.20181965", "CorpusId": 58300215, + "PubMed": "30587505"}, "corpusId": 58300215, "publicationVenue": {"id": "7d071626-1aa2-4dad-a259-bcccedccf44d", + "name": "Journal of Experimental Medicine", "type": "journal", "alternate_names": + ["J Exp Med"], "issn": "0022-1007", "url": "http://www.jem.org/"}, "url": + "https://www.semanticscholar.org/paper/191c5d5e815a92a5073304ffd393c1582dd58b98", + "title": "Toward a better understanding of folate metabolism in health and + disease", "abstract": "In this review, Zheng and Cantley provide a historical + perspective of the folate metabolism field, delve into folate chemistry that + is often overlooked, and point out various missing links and underdeveloped + areas in folate metabolism for future exploration.", "venue": "Journal of + Experimental Medicine", "year": 2018, "referenceCount": 170, "citationCount": + 62, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "https://rupress.org/jem/article-pdf/216/2/253/1171573/jem_20181965.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "2018-12-26", + "journal": {"volume": "216", "pages": "253 - 266", "name": "The Journal of + Experimental Medicine"}, "authors": [{"authorId": "1723564", "name": "Yuxiang + Zheng"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "1aaecc5d195a5efca7681b44e778c29269beeca7", + "externalIds": {"MAG": "2937255160", "CorpusId": 145953224}, "corpusId": 145953224, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/1aaecc5d195a5efca7681b44e778c29269beeca7", + "title": "Targeting PI3K Remains Complex in Cancer Therapy", "abstract": "Dr. + Lewis Cantley discusses targeting the PI3K pathway in breast cancer and the + importance of managing ambient insulin levels during therapy.", "venue": "", + "year": 2018, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2018-12-13", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "2b4ba645fb0855858a2ad6b08edfe2beebe88a2e", "externalIds": {"MAG": + "2889819841", "PubMedCentral": "6155007", "DOI": "10.1038/s41467-018-06377-w", + "CorpusId": 52313304, "PubMed": "30242288"}, "corpusId": 52313304, "publicationVenue": + {"id": "43b3f0f9-489a-4566-8164-02fafde3cd98", "name": "Nature Communications", + "type": "journal", "alternate_names": ["Nat Commun"], "issn": "2041-1723", + "url": "https://www.nature.com/ncomms/", "alternate_urls": ["http://www.nature.com/ncomms/about/index.html", + "http://www.nature.com/ncomms/index.html"]}, "url": "https://www.semanticscholar.org/paper/2b4ba645fb0855858a2ad6b08edfe2beebe88a2e", + "title": "The chromatin remodeler RSF1 controls centromeric histone modifications + to coordinate chromosome segregation", "abstract": null, "venue": "Nature + Communications", "year": 2018, "referenceCount": 48, "citationCount": 14, + "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/s41467-018-06377-w.pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2018-09-21", "journal": {"volume": "9", "name": "Nature + Communications"}, "authors": [{"authorId": "6385088", "name": "Ho-Soo Lee"}, + {"authorId": "49290502", "name": "Zhonghui Lin"}, {"authorId": "36702959", + "name": "S. Chae"}, {"authorId": "48078019", "name": "Young-Suk Yoo"}, {"authorId": + "2151899561", "name": "Byung-Gyu Kim"}, {"authorId": "2145430145", "name": + "Youngsoo Lee"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, {"authorId": + "49171188", "name": "You-Sun Kim"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2145053608", "name": "Chang-Woo Lee"}, {"authorId": "1792198", + "name": "Hongtao Yu"}, {"authorId": "6353303", "name": "Hyeseong Cho"}]}, + {"paperId": "3005e38ea353047f213aeb34d1a8988a57fd2896", "externalIds": {"MAG": + "2810727645", "DOI": "10.1016/j.cmet.2018.06.017", "CorpusId": 49652244, "PubMed": + "29972796"}, "corpusId": 49652244, "publicationVenue": {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", + "name": "Cell Metabolism", "type": "journal", "alternate_names": ["Cell Metab"], + "issn": "1550-4131", "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/15504131", "http://www.cellmetabolism.org/"]}, + "url": "https://www.semanticscholar.org/paper/3005e38ea353047f213aeb34d1a8988a57fd2896", + "title": "A Glycolysis Outsider Steps into the Cancer Spotlight.", "abstract": + null, "venue": "Cell Metabolism", "year": 2018, "referenceCount": 20, "citationCount": + 16, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1550413118303991/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}], "publicationTypes": ["LettersAndComments", + "JournalArticle"], "publicationDate": "2018-07-01", "journal": {"volume": + "28 1", "pages": "\n 3-4\n ", "name": "Cell metabolism"}, + "authors": [{"authorId": "145524334", "name": "M. Goncalves"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "31036b47894196e04618a6c46f77ba2929481ba5", + "externalIds": {"MAG": "2941524734", "CorpusId": 149987512}, "corpusId": 149987512, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/31036b47894196e04618a6c46f77ba2929481ba5", + "title": "Targeting chromosomal instability and downstream cytosolic dna signaling + for cancer treatment", "abstract": "As described herein, chromosomal missegregations, + chromosomal micronuclei, cytosolic DNA, and combinations thereof are indicative + of metastatic cancer. Methods and compositions are described herein that are + useful for detection and treatment of patients with chromosomal instabilities + such as chromosomal missegregations, chromosomal micronuclei, cytosolic DNA, + and combinations thereof. For example, some of the methods and compositions + include use of kinesin-13 proteins such as Kif2b, MCAK/Kif2c, or KIF13A. The + methods and compositions can also include inhibitors of STING, ENPP1, cGAS, + NF-kB transcription factor p52, NF-kB transcription factor RelB, or any combination + thereof. Methods are also described for identifying compounds that are effective + for treatment of cancer, including metastatic cancer.", "venue": "", "year": + 2018, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + null, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5891999", "name": "B. Ngo"}, {"authorId": "3543494", "name": "S. Bakhoum"}]}, + {"paperId": "46e7367392ad6dfc3e99a5e05511e3af8f27363a", "externalIds": {"MAG": + "2782608603", "DOI": "10.1073/pnas.1714703115", "CorpusId": 3445571, "PubMed": + "29311302"}, "corpusId": 3445571, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/46e7367392ad6dfc3e99a5e05511e3af8f27363a", + "title": "Fenofibrate prevents skeletal muscle loss in mice with lung cancer", + "abstract": "Significance The cancer anorexia cachexia syndrome (CACS) is + a condition characterized by skeletal muscle degradation with no effective + treatment. CACS is particularly prevalent in patients with nonsmall cell lung + cancer, where it reduces quality of life and increases mortality. Using an + inducible lung cancer model, we characterize the changes in intermediary metabolism + that occur during CACS in mice. We identify a unique serum metabolite profile + consisting of low ketones and increased glucocorticoid levels. Hypoketonemia + is associated with reduced expression of hepatic peroxisome proliferator-activated + receptor-\u03b1 (PPAR\u03b1) targets that regulate fatty acid oxidation and + ketogenesis. Replacing ketone production using the PPAR\u03b1 agonist, fenofibrate, + reduced glucocorticoid levels, prevented skeletal muscle wasting, and minimized + weight loss. These exciting results provide important preclinical data toward + a therapeutic strategy. The cancer anorexia cachexia syndrome is a systemic + metabolic disorder characterized by the catabolism of stored nutrients in + skeletal muscle and adipose tissue that is particularly prevalent in nonsmall + cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments + and increased mortality. The aim of the present study was to characterize + the changes in systemic metabolism in a genetically engineered mouse model + of NSCLC. We show that a portion of these animals develop loss of skeletal + muscle, loss of adipose tissue, and increased inflammatory markers mirroring + the human cachexia syndrome. Using noncachexic and fasted animals as controls, + we report a unique cachexia metabolite phenotype that includes the loss of + peroxisome proliferator-activated receptor-\u03b1 (PPAR\u03b1) -dependent + ketone production by the liver. In this setting, glucocorticoid levels rise + and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. + Restoring ketone production using the PPAR\u03b1 agonist, fenofibrate, prevents + the loss of skeletal muscle mass and body weight. These results demonstrate + how targeting hepatic metabolism can prevent muscle wasting in lung cancer, + and provide evidence for a therapeutic strategy.", "venue": "Proceedings of + the National Academy of Sciences", "year": 2018, "referenceCount": 79, "citationCount": + 70, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.pnas.org/content/pnas/115/4/E743.full.pdf", "status": + null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2018-01-08", "journal": {"volume": "115", "pages": "E743 + - E752", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "145524334", "name": "M. Goncalves"}, {"authorId": "4151944", + "name": "Seo-Kyoung Hwang"}, {"authorId": "34187590", "name": "C. Pauli"}, + {"authorId": "47107919", "name": "Charles J Murphy"}, {"authorId": "2113278909", + "name": "Zhe Cheng"}, {"authorId": "48821307", "name": "B. Hopkins"}, {"authorId": + "144790190", "name": "David Wu"}, {"authorId": "31875049", "name": "Ryan Loughran"}, + {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": "49288368", "name": + "Guoan Zhang"}, {"authorId": "6971231", "name": "D. Fearon"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "478792c14d32ff2adcc0b2b87975df4fed1038ae", + "externalIds": {"MAG": "2891405227", "DOI": "10.1016/j.cell.2018.08.027", + "CorpusId": 52173591, "PubMed": "30193109"}, "corpusId": 52173591, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/478792c14d32ff2adcc0b2b87975df4fed1038ae", + "title": "The Multifaceted Role of Chromosomal Instability in Cancer and Its + Microenvironment", "abstract": null, "venue": "Cell", "year": 2018, "referenceCount": + 125, "citationCount": 266, "influentialCitationCount": 7, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2018-09-01", "journal": + {"volume": "174", "pages": "1347-1360", "name": "Cell"}, "authors": [{"authorId": + "3543494", "name": "S. Bakhoum"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "5061739e99921c101b56545115e033eb80c25d7d", "externalIds": {"MAG": + "2902716259", "DOI": "10.1021/jacs.8b07911", "CorpusId": 54526289, "PubMed": + "30518210"}, "corpusId": 54526289, "publicationVenue": {"id": "4193a393-c091-455e-858d-3d2c151b52b8", + "name": "Journal of the American Chemical Society", "type": "journal", "alternate_names": + ["J Am Chem Soc"], "issn": "0002-7863", "url": "https://pubs.acs.org/journal/jacsat", + "alternate_urls": ["http://pubs.acs.org/journals/jacsat/index.html", "http://pubs.acs.org/journals/jacsat/"]}, + "url": "https://www.semanticscholar.org/paper/5061739e99921c101b56545115e033eb80c25d7d", + "title": "A Chemoproteomic Strategy for Direct and Proteome-Wide Covalent + Inhibitor Target-Site Identification.", "abstract": "Despite recent clinical + successes for irreversible drugs, potential toxicities mediated by unpredictable + modification of off-target cysteines represents a major hurdle for expansion + of covalent drug programs. Understanding the proteome-wide binding profile + of covalent inhibitors can significantly accelerate their development; however, + current mass spectrometry strategies typically do not provide a direct, amino + acid level readout of covalent activity for complex, selective inhibitors. + Here we report the development of CITe-Id, a novel chemoproteomic approach + that employs covalent pharmacologic inhibitors as enrichment reagents in combination + with an optimized proteomic platform to directly quantify dose-dependent binding + at cysteine-thiols across the proteome. CITe-Id analysis of our irreversible + CDK inhibitor THZ1 identified dose-dependent covalent modification of several + unexpected kinases, including a previously unannotated cysteine (C840) on + the understudied kinase PKN3. These data streamlined our development of JZ128 + as a new selective covalent inhibitor of PKN3. Using JZ128 as a probe compound, + we identified novel potential PKN3 substrates, thus offering an initial molecular + view of PKN3 cellular activity. CITe-Id provides a powerful complement to + current chemoproteomic platforms to characterize the selectivity of covalent + inhibitors, identify new, pharmacologically addressable cysteine-thiols, and + inform structure-based drug design programs.", "venue": "Journal of the American + Chemical Society", "year": 2018, "referenceCount": 66, "citationCount": 49, + "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": {"url": + "https://figshare.com/articles/journal_contribution/A_Chemoproteomic_Strategy_for_Direct_and_Proteome-Wide_Covalent_Inhibitor_Target-Site_Identification/7495778/1/files/13889786.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2018-12-06", "journal": {"volume": + "141 1", "pages": "\n 191-203\n ", "name": "Journal of the + American Chemical Society"}, "authors": [{"authorId": "39374687", "name": + "Christopher M Browne"}, {"authorId": "7864101", "name": "Baishan Jiang"}, + {"authorId": "2297254", "name": "S. Ficarro"}, {"authorId": "47040242", "name": + "Zainab M. Doctor"}, {"authorId": "145916288", "name": "Jared L. Johnson"}, + {"authorId": "5223652", "name": "Joseph D. Card"}, {"authorId": "6443517", + "name": "S. Sivakumaren"}, {"authorId": "33579905", "name": "William M. Alexander"}, + {"authorId": "5247030", "name": "Tomer M. Yaron"}, {"authorId": "47107919", + "name": "Charles J Murphy"}, {"authorId": "6254222", "name": "Nicholas Kwiatkowski"}, + {"authorId": "2262535", "name": "Tinghu Zhang"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "3977406", "name": "N. Gray"}, {"authorId": "2605597", + "name": "J. Marto"}]}, {"paperId": "51794dcdf7ffb5f828868ea533ea9842aa5e9a95", + "externalIds": {"MAG": "2889104327", "DOI": "10.1038/s41586-018-0506-3", "CorpusId": + 52127240, "PubMed": "30158705"}, "corpusId": 52127240, "publicationVenue": + {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/51794dcdf7ffb5f828868ea533ea9842aa5e9a95", + "title": "Publisher Correction: Suppression of insulin feedback enhances the + efficacy of PI3K inhibitors", "abstract": null, "venue": "Nature", "year": + 2018, "referenceCount": 0, "citationCount": 5, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/s41586-018-0506-3.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2018-08-29", "journal": + {"volume": "563", "pages": "E24", "name": "Nature"}, "authors": [{"authorId": + "48821307", "name": "B. Hopkins"}, {"authorId": "34187590", "name": "C. Pauli"}, + {"authorId": "145323219", "name": "Xing Du"}, {"authorId": "152325571", "name": + "Diana G. Wang"}, {"authorId": "48569910", "name": "Xia Li"}, {"authorId": + "144790190", "name": "David Wu"}, {"authorId": "51160946", "name": "Solomon + C. Amadiume"}, {"authorId": "145524334", "name": "M. Goncalves"}, {"authorId": + "7331238", "name": "Cindy Hodakoski"}, {"authorId": "49142390", "name": "Mark + R. Lundquist"}, {"authorId": "9753461", "name": "R. Bareja"}, {"authorId": + "2004581377", "name": "Yan Ma"}, {"authorId": "152768171", "name": "E. M. + Harris"}, {"authorId": "2315866", "name": "A. Sboner"}, {"authorId": "145305292", + "name": "H. Beltran"}, {"authorId": "144014266", "name": "M. Rubin"}, {"authorId": + "49581145", "name": "S. Mukherjee"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "59078b60cc9434b3cea616c21208c0a83ddd3bec", "externalIds": {"MAG": + "2884111611", "PubMedCentral": "6619495", "DOI": "10.1101/370544", "CorpusId": + 92194916, "PubMed": "31091439"}, "corpusId": 92194916, "publicationVenue": + {"id": "027ffd21-ebb0-4af8-baf5-911124292fd0", "name": "bioRxiv", "type": + "journal", "url": "http://biorxiv.org/"}, "url": "https://www.semanticscholar.org/paper/59078b60cc9434b3cea616c21208c0a83ddd3bec", + "title": "PIP4Ks Suppress Insulin Signaling through a Catalytic-Independent + Mechanism", "abstract": "Insulin stimulates conversion of phosphatidylinositol-4,5-bisphosphate + (PI(4,5)P2) to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), which + mediates downstream cellular responses. PI(4,5)P2 is produced by phosphatidylinositol-4-phosphate + 5-kinases (PIP5Ks) and byphosphatidylinositol-5-phosphate 4-kinases (PIP4Ks). + Here we show that deletion of the three genes that encode PIP4Ks (PIP4K2A, + PIP4K2B and PIP4K2C) in vitro results in a paradoxical increase in PI(4,5)P2 + and a subsequent increase in insulin-stimulated production of PI(3,4,5)P3. + Surprisingly, reintroduction of either wild-type or kinase-dead forms of the + PIP4Ks restored cellular PI(4,5)P2 levels and insulin stimulation of the PI3K + pathway. These effects are explained by an increase in PIP5K activity upon + deletion of PIP4Ks, which we demonstrate can suppress PIP5K activity in vitro + through a direct binding interaction. Collectively, our work reveals an important + non-catalytic function of PIP4Ks in suppressing PIP5K-mediated PI(4,5)P2 synthesis + and insulin-dependent conversion to PI(3,4,5)P3 by PI3K enzymes and suggests + that pharmacological depletion of PIP4K enzymes using emerging degrader technologies + could represent a novel strategy for stimulating insulin signaling.", "venue": + "bioRxiv", "year": 2018, "referenceCount": 51, "citationCount": 22, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S2211124719305431/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2018-07-20", "journal": {"volume": "27", "pages": "1991 + - 2001.e5", "name": "Cell reports"}, "authors": [{"authorId": "152325571", + "name": "Diana G. Wang"}, {"authorId": "4422893", "name": "M. Paddock"}, {"authorId": + "49142390", "name": "Mark R. Lundquist"}, {"authorId": "2110677133", "name": + "Janet Y. Sun"}, {"authorId": "13470228", "name": "Oksana Mashadova"}, {"authorId": + "51160946", "name": "Solomon C. Amadiume"}, {"authorId": "15205001", "name": + "Timothy W. Bumpus"}, {"authorId": "7331238", "name": "Cindy Hodakoski"}, + {"authorId": "48821307", "name": "B. Hopkins"}, {"authorId": "48771941", "name": + "Matthew Fine"}, {"authorId": "2072855104", "name": "Amanda Hill"}, {"authorId": + "2115865796", "name": "T. Yang"}, {"authorId": "4863571", "name": "Jeremy + M. Baskin"}, {"authorId": "3918769", "name": "L. Dow"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "693a82eab3e42b59143a343b3018fa3cc3d52fce", + "externalIds": {"MAG": "2885614395", "DOI": "10.1158/1538-7445.AM2018-NG03", + "CorpusId": 81750744}, "corpusId": 81750744, "publicationVenue": {"id": "ad2cb22c-bcde-4ec4-a7a8-503aba675402", + "name": "Tumor Biology", "type": "journal", "issn": "1010-4283", "url": "https://www.karger.com/tbi", + "alternate_urls": ["https://journals.sagepub.com/home/tub", "http://content.karger.com/ProdukteDB/produkte.asp?Aktion=JournalHome&ProduktNr=224124", + "http://www.springer.com/biomed/cancer/journal/13277", "http://link.springer.com/journal/13277", + "https://uk.sagepub.com/en-gb/eur/tumor-biology/journal202707"]}, "url": "https://www.semanticscholar.org/paper/693a82eab3e42b59143a343b3018fa3cc3d52fce", + "title": "Abstract NG03: Chromosomal instability promotes metastasis through + a cytosolic DNA response", "abstract": "Chromosomal instability (CIN) is a + hallmark of cancer and it results from ongoing errors in chromosome segregation + during mitosis. While CIN is a major driver of tumor evolution, its role in + metastasis has not been established. Here we show that CIN promotes metastasis + by sustaining a tumor-cell autonomous response to cytosolic DNA. Errors in + chromosome segregation create a preponderance of micronuclei whose rupture + spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING + cytosolic DNA-sensing pathway and downstream noncanonical NF-\u03baB signaling. + Genetic suppression of CIN significantly delays metastasis even in highly + aneuploid tumor models, whereas inducing continuous chromosome segregation + errors promotes cellular invasion and metastasis in a STING-dependent manner. + Using single-cell RNA sequencing, we uncover a CIN-induced transcriptional + switch from a proliferative and metabolically active state to a mesenchymal + phenotype associated with inflammatory pathways, offering an opportunity to + target chromosome segregation errors for therapeutic benefit. Our work reveals + an unexpected link between CIN, cytosolic DNA sensing pathways, and metastasis. + The use of an isogenic system has enabled us to dissect the role of CIN from + that of aneuploidy. Importantly, while we do not discount the role of CIN + in generating karyotypic heterogeneity that can serve as the substrate for + natural selection, our work demonstrates that continuous chromosome missegregation + is also required to replenish cytosolic DNA pools leading to chronic upregulation + of inflammatory pathways. In non-transformed settings, cytosolic DNA sensing + is incompatible with viability. Unlike normal cells, chromosomally unstable + cells are awash with cytosolic DNA and have adapted to coexist with a chronically + active cGAS-STING pathway by suppressing downstream type I interferon signaling + and instead upregulating the alternative NF-\u03baB pathway. Persistent STING + activation mediates carcinogen-induced tumor formation and we now show that + tumor cells co-opt this otherwise lethal program to spread to distant organs. + The evolutionary benefit of the noncanonical pathway might justify the scarcity + of inactivating mutations in cGAS and STING among human cancers. The emergence, + and subsequent tolerance, of CIN represents an important bottleneck during + tumor evolution. Our single-cell analysis revealed that CIN induces a transcriptional + switch whereby cells shift from a proliferative and highly metabolic state, + ideally suited for primary tumor growth, to a chromosomally unstable and mesenchymal + state associated with upregulation of inflammatory pathways. These two largely + mutually exclusive states likely account for the reversibility in chromosome + missegregation rates seen in primary tumors and metastases, and provide an + explanation for the negative effect of aneuploidy during early tumorigenesis. + Interestingly, this mutual exclusivity was recently observed in a pan-cancer + genomic analysis of metastatic tumors, and it leads us to suggest that CIN + underlies the subset of metastases that are characterized by EMT and inflammation. + By providing a mechanistic link between CIN and metastasis, our work opens + new avenues to target chromosomally unstable tumors for therapeutic benefit. + Citation Format: Samuel F. Bakhoum, Bryon Ngo, Ashley L. Bakhoum, Julie-Ann + Cavallo, Charles J. Murphy, Peter Ly, Pragya Shah, Roshan K. Sriram, Thomas + B.k. Watkins, Neil K. Taunk, Mercedes Duran, Chantal Pauli, Christine Shaw, + Kalyani Chadalavada, Vinagolu K. Rajasekhar, Giulio Genovese, Subramanian + Venkatesan, Nicolai J. Birkbak, Nicholas McGranahan, Mark Lundquist, Quincy + LaPlant, John H. Healey, Olivier Elemento, Christine H. Chung, Nancy Y. Lee, + Marcin Imielinski, Gouri Nanjangud, Dana Pe9er, Don W. Cleveland, Simon N. + Powell, Jan Lammerding, Charles Swanton, Lewis C. Cantley. Chromosomal instability + promotes metastasis through a cytosolic DNA response [abstract]. In: Proceedings + of the American Association for Cancer Research Annual Meeting 2018; 2018 + Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract + nr NG03.", "venue": "Tumor Biology", "year": 2018, "referenceCount": 0, "citationCount": + 2, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2018-07-01", "journal": {"name": + "Tumor Biology"}, "authors": [{"authorId": "3543494", "name": "S. Bakhoum"}, + {"authorId": "87292656", "name": "Bryon Ngo"}, {"authorId": "87660245", "name": + "A. Bakhoum"}, {"authorId": "115814912", "name": "J. Cavallo"}, {"authorId": + "47107919", "name": "Charles J Murphy"}, {"authorId": "50497340", "name": + "P. Ly"}, {"authorId": "30382930", "name": "Pragya Shah"}, {"authorId": "49408849", + "name": "Roshan K. Sriram"}, {"authorId": "3103142", "name": "T. Watkins"}, + {"authorId": "3794250", "name": "N. Taunk"}, {"authorId": "2143838550", "name": + "Mercedes Dur\u00e1n"}, {"authorId": "34187590", "name": "C. Pauli"}, {"authorId": + "145674442", "name": "Christine J. Shaw"}, {"authorId": "8584328", "name": + "K. Chadalavada"}, {"authorId": "5734623", "name": "Vinagolu K. Rajasekhar"}, + {"authorId": "2070205", "name": "G. Genovese"}, {"authorId": "26710439", "name": + "S. Venkatesan"}, {"authorId": "2004080", "name": "N. Birkbak"}, {"authorId": + "5530694", "name": "N. Mcgranahan"}, {"authorId": "49142390", "name": "Mark + R. Lundquist"}, {"authorId": "87374663", "name": "Q. Laplant"}, {"authorId": + "1846047", "name": "J. Healey"}, {"authorId": "150097652", "name": "O. Elemento"}, + {"authorId": "1950427", "name": "C. Chung"}, {"authorId": "47683514", "name": + "N. Y. Lee"}, {"authorId": "46369140", "name": "M. Imieli\u0144ski"}, {"authorId": + "46745715", "name": "G. Nanjangud"}, {"authorId": "1397424343", "name": "D. + Pe\u2019er"}, {"authorId": "144383862", "name": "D. Cleveland"}, {"authorId": + "1695518", "name": "S. Powell"}, {"authorId": "5859625", "name": "J. Lammerding"}, + {"authorId": "145867033", "name": "C. Swanton"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "778cb68cfff551c518564d380d191257f3910f73", "externalIds": + {"MAG": "2803910055", "DOI": "10.1126/scitranslmed.aaq1011", "CorpusId": 44147416, + "PubMed": "29794058"}, "corpusId": 44147416, "publicationVenue": {"id": "1cd4baea-5ccc-4522-9dbf-0566f39d3b37", + "name": "Science Translational Medicine", "type": "journal", "alternate_names": + ["Sci Transl Med"], "issn": "1946-6234", "url": "https://stm.sciencemag.org/", + "alternate_urls": ["https://stm.sciencemag.org/site/misc/about.xhtml"]}, "url": + "https://www.semanticscholar.org/paper/778cb68cfff551c518564d380d191257f3910f73", + "title": "Cancer metabolism gets physical", "abstract": "The physical microenvironment + regulates cancer cell metabolism, and engineered culture systems need to reflect + physical properties of tumors. Patient-derived culture models enable assessment + of drug sensitivity and can connect personalized genomics with therapeutic + options. However, their clinical translation is constrained by limited fidelity. + We outline how the physical microenvironment regulates cell metabolism and + describe how engineered culture systems could enhance the predictive power + for precision medicine.", "venue": "Science Translational Medicine", "year": + 2018, "referenceCount": 61, "citationCount": 29, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc5990021?pdf=render", + "status": null}, "fieldsOfStudy": ["Computer Science", "Medicine"], "s2FieldsOfStudy": + [{"category": "Computer Science", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Engineering", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2018-05-23", "journal": + {"volume": "10", "name": "Science Translational Medicine"}, "authors": [{"authorId": + "15213426", "name": "P. DelNero"}, {"authorId": "48821307", "name": "B. Hopkins"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "143879299", "name": + "C. Fischbach"}]}, {"paperId": "813c657c78657d78edcc87b829f1b631e9d17295", + "externalIds": {"MAG": "2786113733", "DOI": "10.1158/1535-7163.TARG-17-KN01", + "CorpusId": 90306898}, "corpusId": 90306898, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/813c657c78657d78edcc87b829f1b631e9d17295", + "title": "Abstract KN01: Keynote Lecture: PI 3-kinase links obesity, insulin + resistance, and cancer", "abstract": "Phosphoinositide 3-kinase (PI3K) is + activated by insulin and other growth factors to mediate cell growth. The + PI3K enzyme encoded by the PIK3CA gene is one of the most frequently mutated + oncogenes in human cancer. This same enzyme mediates insulin responses in + liver, muscle, fat, and other tissues. The most common mutations in this gene + enhance the ability of PI3K to bind to the insulin receptor substrates, IRS1 + and IRS2, and thereby enhance the ability of PI3K to be activated by insulin + and IGF1. This observation raises the possibility that elevated levels of + serum insulin could enhance the growth of tumors that express the insulin + receptor, especially when the tumor expresses a mutant form of PIK3CA. Consistent + with this idea, retrospective studies have shown that cancers that correlate + with obesity and insulin resistance (conditions where serum insulin levels + are high), such as endometrial, breast, and colorectal cancers, frequently + have activating mutations in PIK3CA. These observations suggest a model in + which tumors with mutations in PIK3CA are highly sensitized to insulin-dependent + growth and that the elevated serum insulin levels in individuals with insulin + resistance in liver, muscle, and fat promote anabolic metabolism in the tumor. + This condition would allow the tumor to take up glucose more readily than + muscle or fat in insulin-resistant individuals. We have generated mouse models + to interrogate the role of PI3Ks in metabolic control and in the generation + of cancers. These studies indicate that inhibitors of PI3Ks could be effective + in treating cancers in specific mutational backgrounds. More than 20 PI3K + inhibitors that target the gene product of PIK3CA have entered clinical trials + for treating solid cancers. Although these inhibitors look promising, a variety + of toxicities have created challenges. Some of the toxicities, such as hyperglycemia, + are on target since inhibition of the PIK3CA gene product is expected to cause + insulin resistance. Importantly, the acute insulin resistance that occurs + in response to PI3K inhibitors not only raises serum glucose levels, but also + induces insulin release from the pancreas, which raises insulin levels. As + discussed above, the increased serum insulin has the potential to activate + PI3K in the tumor, and it is possible that very high insulin levels could + reactivate PI3K in the tumor despite the presence of a PI3K inhibitor. We + have interrogated this possibility in a wide variety of mouse models of cancer + and find that the high serum insulin levels that appear following an oral + dose of a variety of PI3K inhibitors in both human and mouse are sufficient + to activate the PI3K-mTOR signaling pathway. We have utilized multiple therapeutic + interventions in attempts to prevent this rebound of insulin-dependent PI3K + reactivation in tumors, including metformin, a sodium-glucose co-transporter + inhibitor, and a ketogenic diet. We found that the ketogenic diet is more + effective than other therapies at lowering serum insulin levels during PI3K + treatment. Importantly, combining a ketogenic diet with a PI3K inhibitor causes + a dramatic shrinkage of tumors compared to either therapy alone. Citation + Format: Lewis C. Cantley. Keynote Lecture: PI 3-kinase links obesity, insulin + resistance, and cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International + Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, + PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr + KN01.", "venue": "", "year": 2018, "referenceCount": 0, "citationCount": 2, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "17", + "name": "Molecular Cancer Therapeutics"}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "872ac792ca74ee81f00310b0e48a4c6c883d3886", + "externalIds": {"DOI": "10.1096/fasebj.2018.32.1_supplement.250.4", "CorpusId": + 249766482}, "corpusId": 249766482, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/872ac792ca74ee81f00310b0e48a4c6c883d3886", + "title": "Obesity, Insulin Resistance and Cancer: The PI3K connection", "abstract": + "Retrospective studies have revealed that cancer rates in certain organ sites + increase with obesity and some studies have suggested that the subset of obese + individuals who develop insulin resistance are more likely to develop cancers + than those who are obese but remain insulin sensitive. The risk of developing + uterine and breast cancers are particularly high in women who are obese and + insulin resistant and these two cancers have the highest rates of activating + mutations in PIK3CA, the gene that encodes phosphoinositide 3\u2010kinase + 1 alpha (PI3K1alpha). PI3K1alpha mediates insulin dependent cell growth and + the activating mutations in PIK3CA allow this enzyme to be more readily activated + by insulin in tumors that express the insulin receptor. Normal endometrial + and breast epithelial cells express the insulin receptor and tumors in these + tissues often have elevated expression of the insulin receptor. These observations + raise the possibility that the elevated serum insulin in patients who are + insulin resistant may be contributing to the development of tumors, especially + tumors in tissues with PI3K pathway mutations. Many PI3K inhibitors have entered + clinical trials and some have been approved. However, since the inhibitors + that target PI3K1alpha cause insulin resistance in liver, muscle and fat, + they cause hyperglycemia and hyperinsulinemia. Our studies indicate that the + elevated insulin in the serum can ultimately re\u2010activate PI3K1alpha in + the tumor, compromising the effect of these drugs. Strategies for making PI3K + inhibitors more effective by preventing this feedback reactivation of PI3K1alpha + in tumors will be discussed.", "venue": "", "year": 2018, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2018-04-01", "journal": {"volume": + "32", "name": "The FASEB Journal"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "8a1cfa349d0e577c45073a809a9cee520d8a41cd", "externalIds": + {"MAG": "2803030323", "DOI": "10.1016/j.bmcl.2018.04.061", "CorpusId": 19186067, + "PubMed": "29731362"}, "corpusId": 19186067, "publicationVenue": {"id": "56cde9e1-007e-4232-b5ea-ac20f55c39e8", + "name": "Bioorganic & Medicinal Chemistry Letters", "type": "journal", "alternate_names": + ["Bioorganic Med Chem Lett"], "issn": "0960-894X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/972/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/0960894X", + "https://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry"]}, + "url": "https://www.semanticscholar.org/paper/8a1cfa349d0e577c45073a809a9cee520d8a41cd", + "title": "Discovery and optimization of aspartate aminotransferase 1 inhibitors + to target redox balance in pancreatic ductal adenocarcinoma.", "abstract": + null, "venue": "Bioorganic & Medicinal Chemistry Letters", "year": 2018, "referenceCount": + 12, "citationCount": 23, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc6119644?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2018-09-01", "journal": {"volume": + "28 16", "pages": "\n 2675-2678\n ", "name": "Bioorganic & + medicinal chemistry letters"}, "authors": [{"authorId": "35906509", "name": + "J. Anglin"}, {"authorId": "3992718", "name": "R. Zavareh"}, {"authorId": + "46492334", "name": "Philipp N. Sander"}, {"authorId": "41048742", "name": + "Daniel Haldar"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4668673", "name": "A. Kimmelman"}, + {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "6627833", "name": + "L. Lairson"}]}, {"paperId": "912caffb1fd0169c3f0926c8527a1f7ef5e8cfc6", "externalIds": + {"MAG": "2756713090", "DOI": "10.1007/978-3-319-61401-4_2", "CorpusId": 91000193}, + "corpusId": 91000193, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/912caffb1fd0169c3f0926c8527a1f7ef5e8cfc6", + "title": "A topical report on the design principles of metabolism", "abstract": + null, "venue": "", "year": 2018, "referenceCount": 71, "citationCount": 1, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "", "pages": "29-44", + "name": ""}, "authors": [{"authorId": "7745600", "name": "C. Halbrook"}, {"authorId": + "2149418230", "name": "H. Lee"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4901222", "name": "C. Lyssiotis"}]}, {"paperId": "9ece277d9de89d08fd9a3c1322ca7545f9f7ce1b", + "externalIds": {"MAG": "2801628465", "DOI": "10.1016/j.molcel.2018.03.037", + "CorpusId": 19263628, "PubMed": "29727621"}, "corpusId": 19263628, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/9ece277d9de89d08fd9a3c1322ca7545f9f7ce1b", + "title": "Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid + Metabolism By Facilitating Autophagy.", "abstract": null, "venue": "Molecules + and Cells", "year": 2018, "referenceCount": 69, "citationCount": 51, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276518302685/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2018-05-03", "journal": {"volume": + "70 3", "pages": "\n 531-544.e9\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "49142390", "name": "Mark R. Lundquist"}, {"authorId": + "145524334", "name": "M. Goncalves"}, {"authorId": "31875049", "name": "Ryan + Loughran"}, {"authorId": "5353550", "name": "Elite Possik"}, {"authorId": + "48618491", "name": "Tarika Vijayaraghavan"}, {"authorId": "46889299", "name": + "A. Yang"}, {"authorId": "34187590", "name": "C. Pauli"}, {"authorId": "14099966", + "name": "Archna Ravi"}, {"authorId": "40253432", "name": "A. Verma"}, {"authorId": + "50109290", "name": "Zhiwei Yang"}, {"authorId": "145916288", "name": "Jared + L. Johnson"}, {"authorId": "40497062", "name": "Jenny C. Y. Wong"}, {"authorId": + "50032234", "name": "Yilun Ma"}, {"authorId": "41029821", "name": "K. Hwang"}, + {"authorId": "5011109", "name": "D. Weinkove"}, {"authorId": "9277588", "name": + "N. Divecha"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "150097652", + "name": "O. Elemento"}, {"authorId": "144014266", "name": "M. Rubin"}, {"authorId": + "4668673", "name": "A. Kimmelman"}, {"authorId": "4976869", "name": "A. Pause"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5542751", "name": + "B. Emerling"}]}, {"paperId": "b2ddfd54cd0c141201bf6f6b6f0aa1feb2edb737", + "externalIds": {"MAG": "2891117613", "DOI": "10.1158/1538-7445.PRCA2017-A078", + "CorpusId": 81331182}, "corpusId": 81331182, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/b2ddfd54cd0c141201bf6f6b6f0aa1feb2edb737", + "title": "Abstract A078: Towards understanding noncanonical phosphatidylinositol + kinases in the maintenance of prostate metabolism", "abstract": "An estimated + 1 in 7 men will develop prostate cancer (PCa) with many progressing to advanced + castrate-resistant disease. Unlike other tissue types, normal prostate cell + growth and development is heavily dependent on the androgen receptor (AR) + signaling pathway. While the introduction of novel AR antagonists for clinical + treatment has improved outcomes, most castration-resistant prostate cancer + (CRPC) patients ultimately develop resistance to these therapies. A need exists + to better understand the mechanisms that control the transition of prostate + cells from a hormone-dependent to castrate-resistant state. Androgens strongly + influence the metabolic state of PCa cells to favor sustained cellular growth. + We hypothesize there are effectors working in conjunction with AR to coordinate + alterations to androgen-dependent metabolism that are linchpins in the orchestration + of the transition to CRPC. Leading candidates are members of phosphoinositol + (PI) pathways, which have a high frequency of alteration in PCa (i.e phosphoinositide + 3-kinase (PI3K)). Herein we explore a family of poorly understood lipid kinases + called the type II phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks) and + predict them to be critical regulators of cancer cell survival. PI5P4Ks are + druggable targets that act by phosphorylating the lipid phosphatidylinositol-5-phosphate + (PI 5-P) at the 4 position of the inositol ring to generate phosphatidylinositol-4,5-bisphosphate + (PI-4,5-P2; PIP2). We implicate the three PI5P4K isoforms (PI5P4K\u03b1, PI5P4K\u03b2, + and PI5P4K\u03b3) encoded by the genes PIP4K2A, B, and C, to be important + regulators of cancer metabolism that play a role in the maintenance of prostate + biology and oncogenesis. Analysis of transcript data revealed expression of + PIP4K2A, B, and C in primary PCa patient samples, which was correlated with + an AR activation gene signature and hotspot tumor suppressor deletion. As + well, isoform expression was assessed for differential expression in relation + to an integrated neuroendocrine prostate cancer mRNA score (TCGA; n=333). + PI5P4K\u03b1 and PI5P4K\u03b2 protein was detected in primary and advanced + prostate cancer using optimized antibodies of patient tissue TMAs (n= 72). + Using in vitro LNCaP cell models, siRNA knockdown systems were tested to evaluate + the molecular consequence of targeting PIP4K2A and PIP4K2B in androgen-dependent + systems. Stable knockdown using fluorescently labeled lentiviral shRNA constructs + significantly reduced proliferation of shPIP4K2 treated cells. As well, we + have produced a prostate-specific PI5P4K knockout mouse model by expressing + probasin-driven Cre in a homozygous 129/SvEv Pip4k2aflx/flx murine strain. + Finally, implementation of a discovery-based metabolomic platform (Metabolon + HD4) was used to profile the overall shift in metabolite species that results + from downregulating the expression of PIP4K2A in androgen-dependent cell models. + In summary, we have developed novel insights into the role of a family of + noncanonical PI kinases in prostate biology. There are a growing number of + PI3K/AKT inhibitors being tested in combination with androgen deprivation + therapy in clinical trials, but there is still almost nothing known about + the potential crosstalk of the greater PI kinase network. These data convincingly + implicate a fundamental role for PI5P4Ks in PCa androgen signaling and metabolism, + as well as lay the foundation of phenotypic understanding of what PI5P4K is + responsible for in the prostate. Citation Format: Joanna Triscott, Matteo + Benelli, Verena Sailer, Davide Prandi, Brooke Emerling, Francesca Demichelis, + Lewis Cantley, Mark A. Rubin. Towards understanding noncanonical phosphatidylinositol + kinases in the maintenance of prostate metabolism [abstract]. In: Proceedings + of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, + and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): + AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A078.", "venue": "Poster Presentations + - Proffered Abstracts", "year": 2018, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2018-08-14", "journal": {"name": + "Poster Presentations - Proffered Abstracts"}, "authors": [{"authorId": "10334665", + "name": "J. Triscott"}, {"authorId": "1962148", "name": "M. Benelli"}, {"authorId": + "2009967", "name": "V. Sailer"}, {"authorId": "35102567", "name": "D. Prandi"}, + {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": "2382122", "name": + "F. Demichelis"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144014266", "name": "M. Rubin"}]}, {"paperId": "ba63ab40844892ae7a060e1279a1a9f6a902ceb3", + "externalIds": {"MAG": "2801092231", "DOI": "10.1016/j.jid.2018.03.1249", + "CorpusId": 90438620}, "corpusId": 90438620, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/ba63ab40844892ae7a060e1279a1a9f6a902ceb3", + "title": "1234 Vitamin C as a potential treatment for melanoma", "abstract": + null, "venue": "", "year": 2018, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.jidonline.org/article/S0022202X18314751/pdf", "status": null}, + "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2018-05-01", "journal": {"volume": + "138", "name": "Journal of Investigative Dermatology"}, "authors": [{"authorId": + "2056440104", "name": "A. Gade"}, {"authorId": "15358355", "name": "J. Yun"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6765019", "name": + "J. Zippin"}]}, {"paperId": "bc4614b74721a6d0e76c3cdda35cc375db1bb824", "externalIds": + {"MAG": "2898094763", "DOI": "10.1021/acs.biochem.8b00914", "CorpusId": 53099461, + "PubMed": "30365304"}, "corpusId": 53099461, "publicationVenue": {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", + "name": "Biochemistry", "type": "journal", "issn": "0006-2960", "alternate_issns": + ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", "alternate_urls": + ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/bc4614b74721a6d0e76c3cdda35cc375db1bb824", + "title": "Biochemical Characterization and Structure-Based Mutational Analysis + Provide Insight into the Binding and Mechanism of Action of Novel Aspartate + Aminotransferase Inhibitors.", "abstract": "Pancreatic cancer cells are characterized + by deregulated metabolic programs that facilitate growth and resistance to + oxidative stress. Among these programs, pancreatic cancers preferentially + utilize a metabolic pathway through the enzyme aspartate aminotransferase + 1 [also known as glutamate oxaloacetate transaminase 1 (GOT1)] to support + cellular redox homeostasis. As such, small molecule inhibitors that target + GOT1 could serve as starting points for the development of new therapies for + pancreatic cancer. We ran a high-throughput screen for inhibitors of GOT1 + and identified a small molecule, iGOT1-01, with in vitro GOT1 inhibitor activity. + Application in pancreatic cancer cells revealed metabolic and growth inhibitory + activity reflecting a promiscuous inhibitory profile. We then performed an + in silico docking analysis to study inhibitor-GOT1 interactions with iGOT1-01 + analogues that possess improved solubility and potency properties. These results + suggested that the GOT1 inhibitor competed for binding to the pyridoxal 5-phosphate + (PLP) cofactor site of GOT1. To analyze how the GOT1 inhibitor bound to GOT1, + a series of GOT1 mutant enzymes that abolished PLP binding were generated. + Application of the mutants in X-ray crystallography and thermal shift assays + again suggested but were unable to formally conclude that the GOT1 inhibitor + bound to the PLP site. Mutational studies revealed the relationship between + PLP binding and the thermal stability of GOT1 while highlighting the essential + nature of several residues for GOT1 catalytic activity. Insight into the mode + of action of GOT1 inhibitors may provide leads to the development of drugs + that target redox balance in pancreatic cancer.", "venue": "Biochemistry", + "year": 2018, "referenceCount": 31, "citationCount": 20, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://figshare.com/articles/journal_contribution/Biochemical_Characterization_and_Structure-Based_Mutational_Analysis_Provide_Insight_into_the_Binding_and_Mechanism_of_Action_of_Novel_Aspartate_Aminotransferase_Inhibitors/7326998/1/files/13534586.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2018-10-26", "journal": {"volume": + "57 47", "pages": "\n 6604-6614\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "29607220", "name": "M. Holt"}, {"authorId": "13087299", + "name": "Z. Assar"}, {"authorId": "8280749", "name": "Reza B. Beheshti Zavareh"}, + {"authorId": "49478108", "name": "Lin Lin"}, {"authorId": "35906509", "name": + "J. Anglin"}, {"authorId": "13470228", "name": "Oksana Mashadova"}, {"authorId": + "41048742", "name": "Daniel Haldar"}, {"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "40237579", "name": "D. Kremer"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4668673", "name": "A. Kimmelman"}, {"authorId": + "49052322", "name": "A. Stein"}, {"authorId": "6627833", "name": "L. Lairson"}, + {"authorId": "4901222", "name": "C. Lyssiotis"}]}, {"paperId": "be78a2ba227820f0071d1137650094e75e410cde", + "externalIds": {"MAG": "2901442091", "DOI": "10.1056/NEJMra1704560", "CorpusId": + 53752906, "PubMed": "30462943"}, "corpusId": 53752906, "publicationVenue": + {"id": "dc31f077-7737-4e33-baa3-bceeff44ec27", "name": "New England Journal + of Medicine", "type": "journal", "alternate_names": ["n engl J Med", "The + New England Journal of Medicine", "N Engl J Med"], "issn": "0028-4793", "url": + "https://www.nejm.org/", "alternate_urls": ["http://www.nejm.org/content/index.asp", + "http://www.nejm.org/"]}, "url": "https://www.semanticscholar.org/paper/be78a2ba227820f0071d1137650094e75e410cde", + "title": "Phosphatidylinositol 3-Kinase, Growth Disorders, and Cancer.", "abstract": + "The Central Role of PI3K in Cell Signaling Phosphatidylinositol 3-kinase + (PI3K) is involved in multiple cell processes, including insulin signaling, + cell growth, immunity, and brain development. It...", "venue": "New England + Journal of Medicine", "year": 2018, "referenceCount": 0, "citationCount": + 152, "influentialCitationCount": 5, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "2018-11-21", + "journal": {"volume": "379 21", "pages": "\n 2052-2062\n ", + "name": "The New England journal of medicine"}, "authors": [{"authorId": "145524334", + "name": "M. Goncalves"}, {"authorId": "48821307", "name": "B. Hopkins"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "f0a8725403e4e749649595311be501372d99227d", + "externalIds": {"PubMedCentral": "6197057", "MAG": "2809999132", "DOI": "10.1038/s41586-018-0343-4", + "CorpusId": 51724283, "PubMed": "30051890"}, "corpusId": 51724283, "publicationVenue": + {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/f0a8725403e4e749649595311be501372d99227d", + "title": "Suppression of insulin feedback enhances the efficacy of PI3K inhibitors", + "abstract": null, "venue": "Nature", "year": 2018, "referenceCount": 36, "citationCount": + 354, "influentialCitationCount": 13, "isOpenAccess": true, "openAccessPdf": + {"url": "https://boris.unibe.ch/125521/1/nihms-978143.pdf", "status": null}, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2018-06-27", "journal": {"volume": "560", "pages": "499 + - 503", "name": "Nature"}, "authors": [{"authorId": "48821307", "name": "B. + Hopkins"}, {"authorId": "34187590", "name": "C. Pauli"}, {"authorId": "145323219", + "name": "Xing Du"}, {"authorId": "152325571", "name": "Diana G. Wang"}, {"authorId": + "2144438826", "name": "Xiang Li"}, {"authorId": "144790190", "name": "David + Wu"}, {"authorId": "51160946", "name": "Solomon C. Amadiume"}, {"authorId": + "145524334", "name": "M. Goncalves"}, {"authorId": "7331238", "name": "Cindy + Hodakoski"}, {"authorId": "49142390", "name": "Mark R. Lundquist"}, {"authorId": + "9753461", "name": "R. Bareja"}, {"authorId": "2004581377", "name": "Yan Ma"}, + {"authorId": "152768171", "name": "E. M. Harris"}, {"authorId": "2315866", + "name": "A. Sboner"}, {"authorId": "145305292", "name": "H. Beltran"}, {"authorId": + "144014266", "name": "M. Rubin"}, {"authorId": "49581145", "name": "S. Mukherjee"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "face3d1e834aac0eb61f8df3f4929d9b0b64df8a", + "externalIds": {"MAG": "2896543401", "DOI": "10.1038/s41418-018-0213-5", "CorpusId": + 53086490, "PubMed": "30323273"}, "corpusId": 53086490, "publicationVenue": + {"id": "47f0445e-46e2-4685-8244-ddf7c2d587e2", "name": "Cell Death and Differentiation", + "type": "journal", "alternate_names": ["Cell Death Differ", "Cell Death Differ", + "Cell Death & Differentiation"], "issn": "1350-9047", "url": "http://www.nature.com/cdd/", + "alternate_urls": ["http://www.nature.com/cdd/index.html"]}, "url": "https://www.semanticscholar.org/paper/face3d1e834aac0eb61f8df3f4929d9b0b64df8a", + "title": "Consensus report of the 8 and 9th Weinman Symposia on Gene x Environment + Interaction in carcinogenesis: novel opportunities for precision medicine", + "abstract": null, "venue": "Cell Death and Differentiation", "year": 2018, + "referenceCount": 247, "citationCount": 24, "influentialCitationCount": 0, + "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/s41418-018-0213-5.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2018-10-15", "journal": + {"volume": "25", "pages": "1885-1904", "name": "Cell Death & Differentiation"}, + "authors": [{"authorId": "145800854", "name": "M. Carbone"}, {"authorId": + "143937138", "name": "I. Amelio"}, {"authorId": "3916548", "name": "E. Affar"}, + {"authorId": "4185744", "name": "J. Brugarolas"}, {"authorId": "1389506384", + "name": "L. Cannon-Albright"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4140577", "name": "W. Cavenee"}, {"authorId": "1410159779", + "name": "Zhijian J. Chen"}, {"authorId": "144749275", "name": "C. Croce"}, + {"authorId": "1411854449", "name": "Alan D'' Andrea"}, {"authorId": "153754649", + "name": "David Gandara"}, {"authorId": "3571606", "name": "C. Giorgi"}, {"authorId": + "145229527", "name": "Wei Jia"}, {"authorId": "2359692", "name": "Q. Lan"}, + {"authorId": "48696675", "name": "T. Mak"}, {"authorId": "1879130", "name": + "J. Manley"}, {"authorId": "34162721", "name": "K. Mikoshiba"}, {"authorId": + "2110238", "name": "J. Onuchic"}, {"authorId": "2922584", "name": "H. Pass"}, + {"authorId": "3936492", "name": "P. Pinton"}, {"authorId": "2145921", "name": + "C. Prives"}, {"authorId": "144639248", "name": "N. Rothman"}, {"authorId": + "32381915", "name": "S. Sebti"}, {"authorId": "6200449", "name": "J. Turkson"}, + {"authorId": "50171708", "name": "Xifeng Wu"}, {"authorId": "40013732", "name": + "Haining Yang"}, {"authorId": "2621257", "name": "Herbert Yu"}, {"authorId": + "6693964", "name": "G. Melino"}]}, {"paperId": "084308ce6f84792f8eba06150a4c460882b899a0", + "externalIds": {"MAG": "2584068329", "DOI": "10.1038/cdd.2016.114", "CorpusId": + 24656160, "PubMed": "28141794"}, "corpusId": 24656160, "publicationVenue": + {"id": "47f0445e-46e2-4685-8244-ddf7c2d587e2", "name": "Cell Death and Differentiation", + "type": "journal", "alternate_names": ["Cell Death Differ", "Cell Death Differ", + "Cell Death & Differentiation"], "issn": "1350-9047", "url": "http://www.nature.com/cdd/", + "alternate_urls": ["http://www.nature.com/cdd/index.html"]}, "url": "https://www.semanticscholar.org/paper/084308ce6f84792f8eba06150a4c460882b899a0", + "title": "Death-associated protein kinase 1 phosphorylates NDRG2 and induces + neuronal cell death", "abstract": null, "venue": "Cell Death and Differentiation", + "year": 2017, "referenceCount": 59, "citationCount": 35, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/cdd2016114.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2017-02-01", "journal": {"volume": "24", "pages": "238-250", + "name": "Cell Death and Differentiation"}, "authors": [{"authorId": "49529179", + "name": "M. You"}, {"authorId": "145266603", "name": "B. Kim"}, {"authorId": + "120897015", "name": "Chun-Hau Chen"}, {"authorId": "69874482", "name": "M. + Begley"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145569223", + "name": "T. Lee"}]}, {"paperId": "157b5265d7221c692eb32edbd516701a8808ed39", + "externalIds": {"MAG": "2601380465", "DOI": "10.1158/2159-8290.CD-16-1154", + "CorpusId": 13729378, "PubMed": "28331002"}, "corpusId": 13729378, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/157b5265d7221c692eb32edbd516701a8808ed39", + "title": "Personalized In Vitro and In Vivo Cancer Models to Guide Precision + Medicine.", "abstract": "Precision medicine is an approach that takes into + account the influence of individuals'' genes, environment, and lifestyle exposures + to tailor interventions. Here, we describe the development of a robust precision + cancer care platform that integrates whole-exome sequencing with a living + biobank that enables high-throughput drug screens on patient-derived tumor + organoids. To date, 56 tumor-derived organoid cultures and 19 patient-derived + xenograft (PDX) models have been established from the 769 patients enrolled + in an Institutional Review Board-approved clinical trial. Because genomics + alone was insufficient to identify therapeutic options for the majority of + patients with advanced disease, we used high-throughput drug screening to + discover effective treatment strategies. Analysis of tumor-derived cells from + four cases, two uterine malignancies and two colon cancers, identified effective + drugs and drug combinations that were subsequently validated using 3-D cultures + and PDX models. This platform thereby promotes the discovery of novel therapeutic + approaches that can be assessed in clinical trials and provides personalized + therapeutic options for individual patients where standard clinical options + have been exhausted.Significance: Integration of genomic data with drug screening + from personalized in vitro and in vivo cancer models guides precision cancer + care and fuels next-generation research. Cancer Discov; 7(5); 462-77. \u00a92017 + AACR.See related commentary by Picco and Garnett, p. 456This article is highlighted + in the In This Issue feature, p. 443.", "venue": "Cancer Discovery", "year": + 2017, "referenceCount": 46, "citationCount": 565, "influentialCitationCount": + 22, "isOpenAccess": true, "openAccessPdf": {"url": "https://iris.unitn.it/bitstream/11572/175741/1/CD-16-1154_p02-17_LR.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Review"], "publicationDate": "2017-05-01", "journal": {"volume": "7 5", "pages": + "\n 462-477\n ", "name": "Cancer discovery"}, "authors": [{"authorId": + "34187590", "name": "C. Pauli"}, {"authorId": "48821307", "name": "B. Hopkins"}, + {"authorId": "35102567", "name": "D. Prandi"}, {"authorId": "33091056", "name": + "Reid Shaw"}, {"authorId": "5541341", "name": "T. Fedrizzi"}, {"authorId": + "2315866", "name": "A. Sboner"}, {"authorId": "2009967", "name": "V. Sailer"}, + {"authorId": "5658635", "name": "M. Augello"}, {"authorId": "6063687", "name": + "L. Puca"}, {"authorId": "50826946", "name": "R. Rosati"}, {"authorId": "14792558", + "name": "Terra J. McNary"}, {"authorId": "13154644", "name": "Yelena Churakova"}, + {"authorId": "48541155", "name": "C. Cheung"}, {"authorId": "10334665", "name": + "J. Triscott"}, {"authorId": "5528689", "name": "D. Pisapia"}, {"authorId": + "40067278", "name": "R. Rao"}, {"authorId": "4906489", "name": "J. Mosquera"}, + {"authorId": "3239948", "name": "B. Robinson"}, {"authorId": "4328624", "name": + "B. Faltas"}, {"authorId": "14805624", "name": "Brooke E Emerling"}, {"authorId": + "3380008", "name": "V. Gadi"}, {"authorId": "10715010", "name": "Brady Bernard"}, + {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": "145305292", + "name": "H. Beltran"}, {"authorId": "2382122", "name": "F. Demichelis"}, {"authorId": + "3829374", "name": "C. Kemp"}, {"authorId": "6623101", "name": "C. Grandori"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144014266", "name": + "M. 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Dempsey"}, {"authorId": "40508577", "name": + "Yonghao Yu"}, {"authorId": "2118355735", "name": "Xiaolei Liu"}, {"authorId": + "2109324253", "name": "Long He"}, {"authorId": "47026720", "name": "Paola + Cavaliere"}, {"authorId": "2056845844", "name": "Andre Chavez"}, {"authorId": + "3081571", "name": "E. Zhang"}, {"authorId": "4662983", "name": "M. I\u015f\u0131k"}, + {"authorId": "4328102", "name": "A. Couvillon"}, {"authorId": "4622316", "name": + "Noah Dephoure"}, {"authorId": "34098301", "name": "T. Blackwell"}, {"authorId": + "79481462", "name": "Jane J. Yu"}, {"authorId": "35264286", "name": "J. Rabinowitz"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4037343", "name": + "J. 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Ngo"}, {"authorId": "3009053", + "name": "Ashley M. Laughney"}, {"authorId": "115814912", "name": "J. Cavallo"}, + {"authorId": "47107919", "name": "Charles J Murphy"}, {"authorId": "50497340", + "name": "P. Ly"}, {"authorId": "30382930", "name": "Pragya Shah"}, {"authorId": + "49408849", "name": "Roshan K. Sriram"}, {"authorId": "3103142", "name": "T. + Watkins"}, {"authorId": "3794250", "name": "N. Taunk"}, {"authorId": "2143838550", + "name": "Mercedes Dur\u00e1n"}, {"authorId": "34187590", "name": "C. Pauli"}, + {"authorId": "145674442", "name": "Christine J. Shaw"}, {"authorId": "8584328", + "name": "K. Chadalavada"}, {"authorId": "5734623", "name": "Vinagolu K. Rajasekhar"}, + {"authorId": "2070205", "name": "G. Genovese"}, {"authorId": "26710439", "name": + "S. Venkatesan"}, {"authorId": "2004080", "name": "N. Birkbak"}, {"authorId": + "5530694", "name": "N. Mcgranahan"}, {"authorId": "49142390", "name": "Mark + R. Lundquist"}, {"authorId": "152223669", "name": "Q. LaPlant"}, {"authorId": + "1846047", "name": "J. Healey"}, {"authorId": "150097652", "name": "O. Elemento"}, + {"authorId": "1950427", "name": "C. Chung"}, {"authorId": "47683514", "name": + "N. Y. Lee"}, {"authorId": "1398463689", "name": "Marcin Imielenski"}, {"authorId": + "46745715", "name": "G. Nanjangud"}, {"authorId": "1397424343", "name": "D. + Pe\u2019er"}, {"authorId": "144383862", "name": "D. Cleveland"}, {"authorId": + "1695518", "name": "S. Powell"}, {"authorId": "5859625", "name": "J. Lammerding"}, + {"authorId": "145867033", "name": "C. Swanton"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "3c8e19a081a82488e4ec5b759ce993347260df37", "externalIds": + {"MAG": "2623691994", "DOI": "10.1016/j.celrep.2017.05.041", "CorpusId": 3815293, + "PubMed": "28591573"}, "corpusId": 3815293, "publicationVenue": {"id": "a3fb5dc1-0d6e-4cd0-a720-8cb68cbf6486", + "name": "Cell Reports", "type": "journal", "alternate_names": ["Cell Rep"], + "issn": "2211-1247", "url": "https://www.cell.com/cell-reports/home", "alternate_urls": + ["http://cellreports.cell.com/"]}, "url": "https://www.semanticscholar.org/paper/3c8e19a081a82488e4ec5b759ce993347260df37", + "title": "Phosphorylation of TXNIP by AKT Mediates Acute Influx of Glucose + in Response to Insulin.", "abstract": null, "venue": "Cell Reports", "year": + 2017, "referenceCount": 36, "citationCount": 128, "influentialCitationCount": + 9, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S2211124717306836/pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2017-06-06", "journal": + {"volume": "19 10", "pages": "\n 2005-2013\n ", "name": "Cell + reports"}, "authors": [{"authorId": "11625666", "name": "Althea N. Waldhart"}, + {"authorId": "50650966", "name": "Holly Dykstra"}, {"authorId": "46737415", + "name": "Anderson Peck"}, {"authorId": "6560405", "name": "E. Boguslawski"}, + {"authorId": "3814949", "name": "Z. Madaj"}, {"authorId": "50976006", "name": + "Jennifer Wen"}, {"authorId": "13507448", "name": "Kelsey Veldkamp"}, {"authorId": + "14878058", "name": "Matthew T Hollowell"}, {"authorId": "143918840", "name": + "B. Zheng"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "32665208", + "name": "T. McGraw"}, {"authorId": "2068343858", "name": "Ning Wu"}]}, {"paperId": + "3fd230a1b41aba7ee5f6ee1e693d8a2668734694", "externalIds": {"MAG": "2774115269", + "DOI": "10.1158/2159-8290.CD-17-0679", "CorpusId": 4958523, "PubMed": "29203461"}, + "corpusId": 4958523, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/3fd230a1b41aba7ee5f6ee1e693d8a2668734694", + "title": "Identifying and Targeting Sporadic Oncogenic Genetic Aberrations + in Mouse Models of Triple-Negative Breast Cancer.", "abstract": "Triple-negative + breast cancers (TNBC) are genetically characterized by aberrations in TP53 + and a low rate of activating point mutations in common oncogenes, rendering + it challenging in applying targeted therapies. We performed whole-exome sequencing + (WES) and RNA sequencing (RNA-seq) to identify somatic genetic alterations + in mouse models of TNBCs driven by loss of Trp53 alone or in combination with + Brca1 Amplifications or translocations that resulted in elevated oncoprotein + expression or oncoprotein-containing fusions, respectively, as well as frameshift + mutations of tumor suppressors were identified in approximately 50% of the + tumors evaluated. Although the spectrum of sporadic genetic alterations was + diverse, the majority had in common the ability to activate the MAPK/PI3K + pathways. Importantly, we demonstrated that approved or experimental drugs + efficiently induce tumor regression specifically in tumors harboring somatic + aberrations of the drug target. Our study suggests that the combination of + WES and RNA-seq on human TNBC will lead to the identification of actionable + therapeutic targets for precision medicine-guided TNBC treatment.Significance: + Using combined WES and RNA-seq analyses, we identified sporadic oncogenic + events in TNBC mouse models that share the capacity to activate the MAPK and/or + PI3K pathways. Our data support a treatment tailored to the genetics of individual + tumors that parallels the approaches being investigated in the ongoing NCI-MATCH, + My Pathway Trial, and ESMART clinical trials. Cancer Discov; 8(3); 354-69. + \u00a92017 AACR.See related commentary by Natrajan et al., p. 272See related + article by Matissek et al., p. 336This article is highlighted in the In This + Issue feature, p. 253.", "venue": "Cancer Discovery", "year": 2017, "referenceCount": + 81, "citationCount": 48, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://cancerdiscovery.aacrjournals.org/content/candisc/8/3/354.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2017-12-01", "journal": {"volume": + "8 3", "pages": "\n 354-369\n ", "name": "Cancer discovery"}, + "authors": [{"authorId": "2146671919", "name": "Hui Liu"}, {"authorId": "47107919", + "name": "Charles J Murphy"}, {"authorId": "3566950", "name": "F. Karreth"}, + {"authorId": "12967774", "name": "Kristina B. Emdal"}, {"authorId": "8863412", + "name": "F. White"}, {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": + "145751285", "name": "A. Toker"}, {"authorId": "31554501", "name": "G. Wulf"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "40a5f22ea2b26ac49112b1ba1689495e4411e559", + "externalIds": {"MAG": "2741687836", "DOI": "10.1158/1538-7445.AM2017-CT008", + "CorpusId": 79983572}, "corpusId": 79983572, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/40a5f22ea2b26ac49112b1ba1689495e4411e559", + "title": "Abstract CT008: Phase I study of the alpha specific PI3-Kinase inhibitor + BYL719 and the poly (ADP-Ribose) polymerase (PARP) inhibitor olaparib in recurrent + ovarian and breast cancer: Analysis of the dose escalation and ovarian cancer + expansion cohort", "abstract": "Background:In vivo synergy with concurrent + PI3-Kinase inhibition and PARP inhibition has been observed in BRCA-deficient + and BRCA-proficient preclinical models of triple negative breast cancer (TNBC) + and ovarian cancer (OC). A phase I trial of the oral pan-class I PI3-Kinase + inhibitor BKM120 and the PARP inhibitor olaparib demonstrated anti-cancer + activity in TNBC and OC, both in patients with and without germline BRCA1 + and BRCA2 (BRCA) mutations. However, CNS toxicity (depression) and liver function + test abnormalities limited dose escalation of BKM120 prompting evaluation + of the alpha specific PI3-Kinase inhibitor BYL719 (which has no CNS toxicity) + in combination with olaparib. Methods: Olaparib was administered twice daily + (tablet formulation) and BYL719 daily on a 28-day cycle, both orally. A 3 + + 3 dose-escalation design was employed with primary objectives of defining + the maximum tolerated dose (MTD) and recommended phase 2 dose of the combination + of BYL719 and olaparib, and secondary objectives of defining toxicity, activity, + and pharmacokinetic profiles of both agents. Eligibility included recurrent + TNBC or high grade serous (HGS) OC, or any histology OC or breast cancer (BC) + with presence of a known germline BRCA mutation, performance status of 0-1 + and measurable/evaluable cancer. Patients with platinum sensitive or resistant + or refractory OC were eligible and prior PARP inhibitor use was allowed. Dose-expansion + cohorts at the MTD were enrolled for both BC and OC. Results: 46 patients + (16 BC and 30 OC) have been enrolled in the study; 28 patients participated + in the dose escalation portion of the study (4 BC and 24 OC). Two patients + with OC did not receive study drugs because of ineligibility. MTD was defined + as BYL719 200mg once daily and olaparib 200mg twice daily. Dose limiting toxicities + included hyperglycemia, rash and fever with decreased neutrophil count. Four + patients (3 OC and 1 BC) discontinued protocol therapy because of toxicity + (2 for hyperglycemia, 1 for nausea and 1 for allergic reaction). Most common + toxicities included nausea, hyperglycemia, fatigue, diarrhea and vomiting. + At the MTD, 6 patients with OC and 12 patients with BC were enrolled into + a dose expansion cohort. The OC expansion cohort has completed enrollment, + while the BC cohort is still enrolling. Among patients with OC who received + study drugs (28 patients, 26 (93%) with platinum resistant disease), objective + response rate (ORR) by RECIST 1.1 was 36% (10/28 patients, all partial responses + (PRs)). Median duration of response was 167 days (range 16-398 days); 5 of + 10 patients with PR remain on treatment. ORR was 33% for patients with germline + BRCA mutations and 31% for patients without germline BRCA mutations. Among + patients without germline BRCA mutations with platinum resistant OC, ORR was + 29%. Conclusions: Combined BYL719 and olaparib is feasible, and similar clinical + benefit was observed in patients with and without germline BRCA mutations. + The activity of this combination in OC patients without germline BRCA mutations + and with platinum resistant disease was higher than expected from olaparib + monotherapy and warrants further investigation. This work was funded in part + by the Stand Up To Cancer Ovarian Dream Team. Clinical trial: NCT01623349. + Citation Format: Panagiotis A. Konstantinopoulos, William T. Barry, Michael + Birrer, Shannon N. Westin, Sarah Farooq, Karen Cadoo, Christin Whalen, Weixiu + Luo, Hui Liu, Carol Aghajanian, David B. Solit, Gordon B. Mills, Barry S. + Taylor, Helen Won, Michael F. Berger, Sangeetha Palakurthi, Joyce F. Liu, + Lew Cantley, Scott H. Kaufmann, Elizabeth M. Swisher, Alan D. D9Andrea, Eric + Winer, Gerburg M. Wulf, Ursula A. Matulonis. Phase I study of the alpha specific + PI3-Kinase inhibitor BYL719 and the poly (ADP-Ribose) polymerase (PARP) inhibitor + olaparib in recurrent ovarian and breast cancer: Analysis of the dose escalation + and ovarian cancer expansion cohort [abstract]. In: Proceedings of the American + Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, + DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT008. + doi:10.1158/1538-7445.AM2017-CT008", "venue": "", "year": 2017, "referenceCount": + 0, "citationCount": 4, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2017-07-01", "journal": {"volume": + "77", "name": "Cancer Research"}, "authors": [{"authorId": "49610180", "name": + "P. Konstantinopoulos"}, {"authorId": "143997654", "name": "W. Barry"}, {"authorId": + "2167106", "name": "M. Birrer"}, {"authorId": "2974900", "name": "S. Westin"}, + {"authorId": "7862178", "name": "S. Farooq"}, {"authorId": "5372086", "name": + "K. Cadoo"}, {"authorId": "122974814", "name": "C. Whalen"}, {"authorId": + "4146119", "name": "W. Luo"}, {"authorId": "2146671919", "name": "Hui Liu"}, + {"authorId": "6128162", "name": "C. Aghajanian"}, {"authorId": "2344124", + "name": "D. Solit"}, {"authorId": "2241330", "name": "G. Mills"}, {"authorId": + "36898514", "name": "B. Taylor"}, {"authorId": "3738649", "name": "H. Won"}, + {"authorId": "33727638", "name": "M. Berger"}, {"authorId": "32453098", "name": + "S. Palakurthi"}, {"authorId": "2108419806", "name": "Joyce F. Liu"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144100151", "name": "S. Kaufmann"}, + {"authorId": "3733822", "name": "E. Swisher"}, {"authorId": "1396108662", + "name": "A. D\u2019Andrea"}, {"authorId": "2369378", "name": "E. Winer"}, + {"authorId": "31554501", "name": "G. Wulf"}, {"authorId": "6927295", "name": + "U. Matulonis"}]}, {"paperId": "4d84a4d0ca3b007f4812a6e1f5acaf220c6dc124", + "externalIds": {"DOI": "10.1074/jbc.A117.305602", "CorpusId": 46526155, "PubMed": + "28363934"}, "corpusId": 46526155, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/4d84a4d0ca3b007f4812a6e1f5acaf220c6dc124", + "title": "Positive and negative roles of p85\u03b1 and p85\u03b2 regulatory + subunits of phosphoinositide 3-kinase in insulin signaling.", "abstract": + "Kohjiro Ueki, David A. Fruman, Claudine M. Yballe, Mathias Fasshauer, Johannes + Klein, Tomoichiro Asano, Lewis C. Cantley, and C. Ronald Kahn This article + has been withdrawn by the authors. In many of the experiments reported in + this study, cells from mice of four genotypes were used (wild-type, p85 / + , p85 / , and p85 / ), but data from only three of the genotypes (wild-type, + p85 / , and p85 / ) were included in the final paper. As a result, there was + splicing of the figures of several autoradiograms, which led to several duplicated + or mislabeled lanes in the Western blots in Figs. 2B, 3C, and 5B. Although + the experimental data generated in the lab from the same time period support + the original conclusions of the study, and the studies by this lab and others + have confirmed and extended the conclusions of the manuscript, in the interest + of maintaining accuracy in the published scientific literature and because + the initial figures were not up to the standards of JBC, the authors wish + to withdraw this article. The authors apologize for these errors. THE JOURNAL + OF BIOLOGICAL CHEMISTRY VOL. 292, NO. 13, p. 5608, March 31, 2017 \u00a9 2017 + by The American Society for Biochemistry and Molecular Biology, Inc. Published + in the U.S.A.", "venue": "Journal of Biological Chemistry", "year": 2017, + "referenceCount": 0, "citationCount": 23, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.jbc.org/content/292/13/5608.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2017-03-31", "journal": + {"volume": "292", "pages": "5608 - 5608", "name": "The Journal of Biological + Chemistry"}, "authors": [{"authorId": "5177377", "name": "K. Ueki"}, {"authorId": + "6241317", "name": "D. Fruman"}, {"authorId": "7777071", "name": "C. Yballe"}, + {"authorId": "48775825", "name": "M. Fasshauer"}, {"authorId": "50073811", + "name": "J. Klein"}, {"authorId": "1928077", "name": "T. Asano"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": "C. Kahn"}]}, + {"paperId": "5dc3dc62e4a1be481565d0494cc7c723e8285816", "externalIds": {"MAG": + "2783642736", "DOI": "10.1016/J.CCELL.2017.08.008", "CorpusId": 203876604}, + "corpusId": 203876604, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/5dc3dc62e4a1be481565d0494cc7c723e8285816", + "title": "Erratum: MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic + Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer (Cancer + Cell (2017) 32(1) (71\u201387.e7) (S1535610817302544) (10.1016/j.ccell.2017.06.004))", + "abstract": null, "venue": "", "year": 2017, "referenceCount": 0, "citationCount": + 33, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1535610817303525/pdf", "status": null}, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2017-09-11", "journal": {"volume": + "32", "name": "Cancer Cell"}, "authors": [{"authorId": "5313024", "name": + "S. Shukla"}, {"authorId": "40401242", "name": "V. Purohit"}, {"authorId": + "6262895", "name": "Kamiya Mehla"}, {"authorId": "3474931", "name": "V. Gunda"}, + {"authorId": "12164048", "name": "Nina V. Chaika"}, {"authorId": "4197522", + "name": "E. Vernucci"}, {"authorId": "14809253", "name": "Ryan J. King"}, + {"authorId": "6519716", "name": "J. Abrego"}, {"authorId": "40498919", "name": + "G. Goode"}, {"authorId": "4198255", "name": "Aneesha Dasgupta"}, {"authorId": + "19371882", "name": "Alysha L. Illies"}, {"authorId": "50019590", "name": + "T. Gebregiworgis"}, {"authorId": "39746276", "name": "B. Dai"}, {"authorId": + "47024265", "name": "Jithesh J. Augustine"}, {"authorId": "48665899", "name": + "Divya Murthy"}, {"authorId": "12496228", "name": "K. Attri"}, {"authorId": + "13470228", "name": "Oksana Mashadova"}, {"authorId": "6621353", "name": "P. + Grandgenett"}, {"authorId": "145461840", "name": "R. Powers"}, {"authorId": + "14222342", "name": "Q. Ly"}, {"authorId": "3652387", "name": "A. Lazenby"}, + {"authorId": "4068345", "name": "J. Grem"}, {"authorId": "145120646", "name": + "F. Yu"}, {"authorId": "35070687", "name": "J. Mat\u00e9s"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "2110838079", "name": "Jung Whan + Kim"}, {"authorId": "5866146", "name": "J. Hankins"}, {"authorId": "143872276", + "name": "C. Weekes"}, {"authorId": "38154576", "name": "M. Hollingsworth"}, + {"authorId": "6361174", "name": "N. Serkova"}, {"authorId": "3803395", "name": + "A. Sasson"}, {"authorId": "144926646", "name": "J. Fleming"}, {"authorId": + "4425897", "name": "J. Oliveto"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "11588674", "name": + "L. Berim"}, {"authorId": "144633198", "name": "P. Singh"}]}, {"paperId": + "76b4925dfbd2860f7c6ec27ad7baade4273ffb8d", "externalIds": {"MAG": "2737327904", + "DOI": "10.1016/j.celrep.2017.06.074", "CorpusId": 4633189, "PubMed": "28723573"}, + "corpusId": 4633189, "publicationVenue": {"id": "a3fb5dc1-0d6e-4cd0-a720-8cb68cbf6486", + "name": "Cell Reports", "type": "journal", "alternate_names": ["Cell Rep"], + "issn": "2211-1247", "url": "https://www.cell.com/cell-reports/home", "alternate_urls": + ["http://cellreports.cell.com/"]}, "url": "https://www.semanticscholar.org/paper/76b4925dfbd2860f7c6ec27ad7baade4273ffb8d", + "title": "Proteomic and Metabolomic Characterization of a Mammalian Cellular + Transition from Quiescence to Proliferation.", "abstract": null, "venue": + "Cell Reports", "year": 2017, "referenceCount": 72, "citationCount": 28, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S2211124717309051/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2017-07-18", "journal": {"volume": + "20 3", "pages": "\n 721-736\n ", "name": "Cell reports"}, + "authors": [{"authorId": "49923389", "name": "Ho-Joon Lee"}, {"authorId": + "6432355", "name": "Mark P. Jedrychowski"}, {"authorId": "34371262", "name": + "A. Vinayagam"}, {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": + "1397529716", "name": "Ng Shyh\u2010Chang"}, {"authorId": "2228212", "name": + "Yanhui Hu"}, {"authorId": "1436554412", "name": "Chua Min-Wen"}, {"authorId": + "88429432", "name": "Jodene K Moore"}, {"authorId": "3028470", "name": "J. + Asara"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "2001255", + "name": "N. Perrimon"}, {"authorId": "2665934", "name": "S. Gygi"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "40294231", "name": "M. Kirschner"}]}, + {"paperId": "7bdd02d199d9c3bd5f649d2fe639d9efa6ba99bd", "externalIds": {"MAG": + "2780640138", "DOI": "10.1158/1078-0432.CCR-17-2141", "CorpusId": 3494231, + "PubMed": "29284706"}, "corpusId": 3494231, "publicationVenue": {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", + "name": "Clinical Cancer Research", "type": "journal", "alternate_names": + ["Clin Cancer Res"], "issn": "1078-0432", "url": "https://clincancerres.aacrjournals.org/", + "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/7bdd02d199d9c3bd5f649d2fe639d9efa6ba99bd", + "title": "PIK3CA C2 Domain Deletions Hyperactivate Phosphoinositide 3-kinase + (PI3K), Generate Oncogene Dependence, and Are Exquisitely Sensitive to PI3K\u03b1 + Inhibitors", "abstract": "Purpose: We describe herein a novel P447_L455 deletion + in the C2 domain of PIK3CA in a patient with an ER+ breast cancer with an + excellent response to the PI3K\u03b1 inhibitor alpelisib. Although PIK3CA + deletions are relatively rare, a significant portion of deletions cluster + within amino acids 446\u2013460 of the C2 domain, suggesting these residues + are critical for p110\u03b1 function. Experimental Design: A computational + structural model of PIK3CAdelP447-L455 in complex with the p85 regulatory + subunit and MCF10A cells expressing PIK3CAdelP447-L455 and PIK3CAH450_P458del + were used to understand the phenotype of C2 domain deletions. Results: Computational + modeling revealed specific favorable inter-residue contacts that would be + lost as a result of the deletion, predicting a significant decrease in binding + energy. Coimmunoprecipitation experiments showed reduced binding of the C2 + deletion mutants with p85 compared with wild-type p110\u03b1. The MCF10A cells + expressing PIK3CA C2 deletions exhibited growth factor\u2013independent growth, + an invasive phenotype, and higher phosphorylation of AKT, ERK, and S6 compared + with parental MCF10A cells. All these changes were ablated by alpelisib treatment. + Conclusions: C2 domain deletions in PIK3CA generate PI3K dependence and should + be considered biomarkers of sensitivity to PI3K inhibitors. Clin Cancer Res; + 24(6); 1426\u201335. \u00a92017 AACR.", "venue": "Clinical Cancer Research", + "year": 2017, "referenceCount": 37, "citationCount": 18, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://clincancerres.aacrjournals.org/content/clincanres/24/6/1426.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2017-12-28", "journal": + {"volume": "24", "pages": "1426 - 1435", "name": "Clinical Cancer Research"}, + "authors": [{"authorId": "5404128", "name": "Sarah Croessmann"}, {"authorId": + "6251014", "name": "J. Sheehan"}, {"authorId": "46542827", "name": "Kyung-Min + Lee"}, {"authorId": "3381467", "name": "Gregory Sliwoski"}, {"authorId": "50774890", + "name": "Ji\u00e9 He"}, {"authorId": "39540895", "name": "R. Nagy"}, {"authorId": + "82059310", "name": "David A. Riddle"}, {"authorId": "2346140", "name": "I. + Mayer"}, {"authorId": "66935619", "name": "J. Balko"}, {"authorId": "3484938", + "name": "R. Lanman"}, {"authorId": "2134288", "name": "V. Miller"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "1754226", "name": "J. Meiler"}, + {"authorId": "2057460", "name": "C. Arteaga"}]}, {"paperId": "861c629752fa0f201872ce88465b1beb643228fe", + "externalIds": {"MAG": "2739659697", "DOI": "10.1158/1538-7445.am2017-1772", + "CorpusId": 57106791}, "corpusId": 57106791, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/861c629752fa0f201872ce88465b1beb643228fe", + "title": "Abstract 1772:PIK3CAC2 domain deletions hyperactivate PI3K, generate + oncogene dependence and are exquisitely sensitive to PI3K\u03b1 inhibitors", + "abstract": null, "venue": "", "year": 2017, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2017-07-01", "journal": {"volume": + "77", "pages": "1772-1772", "name": "Cancer Research"}, "authors": [{"authorId": + "5404128", "name": "Sarah Croessmann"}, {"authorId": "6251014", "name": "J. + Sheehan"}, {"authorId": "3381467", "name": "Gregory Sliwoski"}, {"authorId": + "8805251", "name": "Nalin Leelatian"}, {"authorId": "50774890", "name": "Ji\u00e9 + He"}, {"authorId": "39540895", "name": "R. Nagy"}, {"authorId": "66935619", + "name": "J. Balko"}, {"authorId": "2346140", "name": "I. Mayer"}, {"authorId": + "3484938", "name": "R. Lanman"}, {"authorId": "2134288", "name": "V. Miller"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "46512580", "name": + "J. Irish"}, {"authorId": "1754226", "name": "J. Meiler"}, {"authorId": "2057460", + "name": "C. Arteaga"}]}, {"paperId": "8d23d27e574721b07c07c4ae65412b3bb3f3eb89", + "externalIds": {"MAG": "2744377419", "DOI": "10.1016/j.cell.2017.07.029", + "CorpusId": 5283960, "PubMed": "28802037"}, "corpusId": 5283960, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/8d23d27e574721b07c07c4ae65412b3bb3f3eb89", + "title": "The PI3K Pathway in Human Disease", "abstract": null, "venue": "Cell", + "year": 2017, "referenceCount": 294, "citationCount": 1242, "influentialCitationCount": + 57, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867417308656/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "2017-08-10", "journal": {"volume": "170", "pages": "605-635", + "name": "Cell"}, "authors": [{"authorId": "6241317", "name": "D. Fruman"}, + {"authorId": "16259488", "name": "Honyin Chiu"}, {"authorId": "48821307", + "name": "B. Hopkins"}, {"authorId": "4229053", "name": "S. Bagrodia"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3148968", "name": "R. Abraham"}]}, + {"paperId": "8d37a19158675e90cbdb34494270226c8eac3e46", "externalIds": {"PubMedCentral": + "5426642", "MAG": "2595206365", "DOI": "10.1016/j.molcel.2017.02.019", "CorpusId": + 3918156, "PubMed": "28306514"}, "corpusId": 3918156, "publicationVenue": {"id": + "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", "type": + "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": "1016-8478", + "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/8d37a19158675e90cbdb34494270226c8eac3e46", + "title": "PARK2 Depletion Connects Energy and Oxidative Stress to PI3K/Akt + Activation via PTEN S-Nitrosylation", "abstract": null, "venue": "Molecules + and Cells", "year": 2017, "referenceCount": 71, "citationCount": 89, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S109727651730134X/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2017-03-16", "journal": {"volume": + "65", "pages": "999 - 1013.e7", "name": "Molecular Cell"}, "authors": [{"authorId": + "2143746859", "name": "Amit Gupta"}, {"authorId": "1422350224", "name": "S. + Anjomani-Virmouni"}, {"authorId": "13532971", "name": "Nikos Koundouros"}, + {"authorId": "49235150", "name": "M. Dimitriadi"}, {"authorId": "1401641678", + "name": "R. Choo-Wing"}, {"authorId": "115137674", "name": "A. Valle"}, {"authorId": + "1723564", "name": "Yuxiang Zheng"}, {"authorId": "47591147", "name": "Y. + Chiu"}, {"authorId": "144901810", "name": "S. Agnihotri"}, {"authorId": "98462145", + "name": "G. Zadeh"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "46996935", "name": "D. Anastasiou"}, {"authorId": "118353344", "name": "M. + Arends"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4612853", + "name": "G. Poulogiannis"}]}, {"paperId": "8e98f4dac7ecd14346a16290b4b4e96a56a894ea", + "externalIds": {"MAG": "3024001711", "DOI": "10.1182/BLOOD.V130.SUPPL_1.643.643", + "CorpusId": 220333008}, "corpusId": 220333008, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/8e98f4dac7ecd14346a16290b4b4e96a56a894ea", + "title": "SIRT3 Is a Novel Metabolic Driver of and Therapeutic Target for + Chemotherapy Resistant Dlbcls", "abstract": "Understanding the molecular basis + of therapy-resistant DLBCL is a critical unmet need. We explored whether the + family of Sirtuin proteins might contribute to such effects. Analysis of four + independent clinically annotated patient cohorts revealed that higher SIRT3 + expression was linked to inferior outcome (p=4.7e-5). This was not the case + for any other of the sirtuins. SIRT3 mRNA and protein expression were also + much higher in DLBCL patients as compared to normal germinal center (GC) B-cells. + Among the seven sirtuins, only SIRT3 depletion universally suppressed proliferation, + induced cell cycle arrest, suppressed colony formation, and induced apoptosis + in a large panel of DLBCL cell lines regardless of cell of origin, OxPhos + status, or somatic mutation profiles. Constitutive Sirt3-/- mice manifested + completely normal GC formation after T-cell dependent antigen immunization. + However SIRT3 depleted human DLBCL cells manifested inferior engraftment and + tumor formation in mice (p=0.023 for hairpin#1, p=0.045 for hairpin#2). Sirt3 + inducible knockdown caused strong regression of established DLBCL xenografts. + We examined whether SIRT3 was important in lymphoma initiation by crossing + VavP-Bcl2 mice with Sirt3-/- animals. As compared to VavP-Bcl2 controls, the + VavP-Bcl2/Sirt3-/- mice manifested significantly longer overall survival (P=0.0035), + and greatly reduced tumor burden and systemic lymphoma infiltration of organs. + SIRT3 is exclusively localized to mitochondria and hence its actions are likely + metabolic. We therefore performed metabolomic profiling in SIRT 3 depleted + DLBCL cell lines. This analysis revealed profound suppression of the TCA (tricarboxylic + acid) cycle, with reduced TCA metabolites such as citrate, alpha-ketoglutarate, + succinate, fumarate, malate, etc. SIRT3 depletion caused significant reduction + in acetyl-CoA pools as measured by solid phase extraction and LC-MS, indicating + that SIRT3 is required to maintain the production of key metabolic intermediates + from the TCA cycle. To define the nature of the TCA defect we performed metabolic + tracing studies using 13C-labeled glutamine and glucose. The results revealed + that SIRT3 drives the TCA cycle through glutaminolysis. We showed that SIRT3 + mediates this effect by directly deacetylating and hence hyper-activating + the enzymatic activity of mitochondrial glutamine dehydrogenase (GDH). Indeed + GDH overexpression could fully rescue the collapse of the TCA, cell proliferation + arrest and apoptosis induced by SIRT3 depletion. SIRT3 knockdown was also + rescued by feeding cells DMKG (which mimics alpha-ketoglutarate) and hence + bypasses the need for SIRT3 mediated glutaminolysis. Because SIRT3 depletion + caused metabolic collapse, DLBCL cells manifested potent induction of autophagy, + as shown by ratios of LC3II/LC3I in DLBCL cells and using a mCherry-EGFP-LC3 + reporter to measure autophagic flux. This autophagy effect was rescued by + feeding cells with DMKG or by overexpressing GDH, which uncouple the TCA cycle + from SIRT3 dependency. Notably the ratio of LC3II/LCI and perturbed autophagy + flux was also Increased in lymphoma cells from VavP-Bcl2;sirt3-/- vs. VavP-Bcl2;sirt3+/+ + mice. These data nominate SIRT3 as a putative therapeutic target. Therefore + we designed a nanomolar-potency SIRT3 selective small molecule inhibitor including + a mitochondrial-targeting motif that concentrates drug in the mitochondrial + matrix. This compound (called YC8-02), phenocopied all the effects of SIRT3 + depletion including proliferation arrest, apoptosis, TCA collapse by metabolomics + study, hyperacetylation of mitochondrial proteins, suppression of GDH activity, + and induction of autophagy. Yet YC8-02 had no effect on normal B-cells. Moreover, + YC8-02 treatment of chemotherapy resistant DLBCL cell lines restored their + sensitivity to clinically relevant doxorubicin concentrations. In summary, + SIRT3 is a novel metabolic oncoprotein widely required for DLBCL cells to + satisfy their metabolic needs by enhancing the activity of the TCA cycle through + glutaminolysis. SIRT3 is a crucial new therapeutic vulnerability especially + impactful for the most resistant DLBCLs regardless of their somatic mutations. + YC8-02 and its newer derivatives are a promising and entirely new mechanism-based + approach to help these patients. Disclosures Cerchietti: Leukemia and Lymphoma + Society: Research Funding; Lymphoma Research Foundation: Research Funding; + Weill Cornell Medicine - New York Presbyterian Hospital: Employment; Celgene: + Research Funding.", "venue": "", "year": 2017, "referenceCount": 0, "citationCount": + 3, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2017-12-07", "journal": {"volume": + "130", "pages": "643-643", "name": "Blood"}, "authors": [{"authorId": "88436340", + "name": "M. Li"}, {"authorId": "50462482", "name": "Ying-Ling Chiang"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "79496189", "name": "Matt + Teater"}, {"authorId": "2110770666", "name": "Hao Shen"}, {"authorId": "2151978477", + "name": "Ling Wang"}, {"authorId": "47728412", "name": "J. Hong"}, {"authorId": + "2109930096", "name": "Hui Jin"}, {"authorId": "145546240", "name": "C. Duy"}, + {"authorId": "36529561", "name": "S. Mistry"}, {"authorId": "6791438", "name": + "L. Cerchietti"}, {"authorId": "4001772", "name": "J. Cross"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "35643033", "name": "Hening + Lin"}, {"authorId": "145150236", "name": "A. Melnick"}]}, {"paperId": "9c85b5c1b1da70b90109fde12ebef63d0e2728f0", + "externalIds": {"MAG": "2590621600", "DOI": "10.1158/2159-8290.CD-16-0612", + "CorpusId": 4528396, "PubMed": "28255082"}, "corpusId": 4528396, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/9c85b5c1b1da70b90109fde12ebef63d0e2728f0", + "title": "PTEN Regulates Glutamine Flux to Pyrimidine Synthesis and Sensitivity + to Dihydroorotate Dehydrogenase Inhibition.", "abstract": "Metabolic changes + induced by oncogenic drivers of cancer contribute to tumor growth and are + attractive targets for cancer treatment. Here, we found that increased growth + of PTEN-mutant cells was dependent on glutamine flux through the de novo pyrimidine + synthesis pathway, which created sensitivity to the inhibition of dihydroorotate + dehydrogenase, a rate-limiting enzyme for pyrimidine ring synthesis. S-phase + PTEN-mutant cells showed increased numbers of replication forks, and inhibitors + of dihydroorotate dehydrogenase led to chromosome breaks and cell death due + to inadequate ATR activation and DNA damage at replication forks. Our findings + indicate that enhanced glutamine flux generates vulnerability to dihydroorotate + dehydrogenase inhibition, which then causes synthetic lethality in PTEN-deficient + cells due to inherent defects in ATR activation. Inhibition of dihydroorotate + dehydrogenase could thus be a promising therapy for patients with PTEN-mutant + cancers.Significance: We have found a prospective targeted therapy for PTEN-deficient + tumors, with efficacy in vitro and in vivo in tumors derived from different + tissues. This is based upon the changes in glutamine metabolism, DNA replication, + and DNA damage response which are consequences of inactivation of PTENCancer + Discov; 7(4); 380-90. \u00a92017 AACR.See related article by Brown et al., + p. 391This article is highlighted in the In This Issue feature, p. 339.", + "venue": "Cancer Discovery", "year": 2017, "referenceCount": 35, "citationCount": + 72, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "https://academiccommons.columbia.edu/doi/10.7916/D8CN7BPR/download", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2017-03-02", "journal": {"volume": + "7 4", "pages": "\n 380-390\n ", "name": "Cancer discovery"}, + "authors": [{"authorId": "1683686", "name": "Deepti Mathur"}, {"authorId": + "50738000", "name": "E. Stratikopoulos"}, {"authorId": "6487574", "name": + "Sait Ozturk"}, {"authorId": "5694306", "name": "Nicole Steinbach"}, {"authorId": + "7475438", "name": "Sarah Pegno"}, {"authorId": "15429457", "name": "Sarah + M. Schoenfeld"}, {"authorId": "5170353", "name": "R. Yong"}, {"authorId": + "145900083", "name": "V. Murty"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "47689907", "name": + "R. Parsons"}]}, {"paperId": "a613e2e4da7aeb2c4e004760afddf8f7bd42d3cd", "externalIds": + {"MAG": "2757659639", "DOI": "10.1016/j.ijrobp.2017.06.500", "CorpusId": 79825464}, + "corpusId": 79825464, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/a613e2e4da7aeb2c4e004760afddf8f7bd42d3cd", + "title": "Radiation-Induced Activation of Innate Immune Pathways from Errors + in Mitosis", "abstract": null, "venue": "", "year": 2017, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.redjournal.org/article/S0360301617315523/pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2017-10-01", "journal": {"volume": + "99", "name": "International Journal of Radiation Oncology Biology Physics"}, + "authors": [{"authorId": "3543494", "name": "S. Bakhoum"}, {"authorId": "5891999", + "name": "B. Ngo"}, {"authorId": "87660245", "name": "A. Bakhoum"}, {"authorId": + "1435148670", "name": "J. Cavallo-Fleming"}, {"authorId": "47107919", "name": + "Charles J Murphy"}, {"authorId": "1695518", "name": "S. Powell"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "a7fabb6e6de2ef2519b0262ddea066b5d98dd616", + "externalIds": {"DOI": "10.1016/j.ccell.2017.08.008", "CorpusId": 2812197, + "PubMed": "28898700"}, "corpusId": 2812197, "publicationVenue": {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", + "name": "Cancer Cell", "type": "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/a7fabb6e6de2ef2519b0262ddea066b5d98dd616", + "title": "MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose + Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer.", "abstract": + null, "venue": "Cancer Cell", "year": 2017, "referenceCount": 0, "citationCount": + 107, "influentialCitationCount": 4, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1535610817303525/pdf", "status": null}, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": null, "journal": + {"volume": "32 3", "pages": "\n 392\n ", "name": "Cancer cell"}, + "authors": [{"authorId": "5313024", "name": "S. Shukla"}, {"authorId": "40401242", + "name": "V. Purohit"}, {"authorId": "6262895", "name": "Kamiya Mehla"}, {"authorId": + "3474931", "name": "V. Gunda"}, {"authorId": "12164048", "name": "Nina V. + Chaika"}, {"authorId": "4197522", "name": "E. Vernucci"}, {"authorId": "14809253", + "name": "Ryan J. King"}, {"authorId": "6519716", "name": "J. Abrego"}, {"authorId": + "40498919", "name": "G. Goode"}, {"authorId": "4198255", "name": "Aneesha + Dasgupta"}, {"authorId": "19371882", "name": "Alysha L. Illies"}, {"authorId": + "50019590", "name": "T. Gebregiworgis"}, {"authorId": "39746276", "name": + "B. Dai"}, {"authorId": "47024265", "name": "Jithesh J. Augustine"}, {"authorId": + "48665899", "name": "Divya Murthy"}, {"authorId": "12496228", "name": "K. + Attri"}, {"authorId": "13470228", "name": "Oksana Mashadova"}, {"authorId": + "6621353", "name": "P. Grandgenett"}, {"authorId": "145461840", "name": "R. + Powers"}, {"authorId": "14222342", "name": "Q. Ly"}, {"authorId": "3652387", + "name": "A. Lazenby"}, {"authorId": "4068345", "name": "J. Grem"}, {"authorId": + "145120646", "name": "F. Yu"}, {"authorId": "35070687", "name": "J. Mat\u00e9s"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "2110045806", "name": + "Jung-whan Kim"}, {"authorId": "5866146", "name": "J. Hankins"}, {"authorId": + "143872276", "name": "C. Weekes"}, {"authorId": "38154576", "name": "M. Hollingsworth"}, + {"authorId": "6361174", "name": "N. Serkova"}, {"authorId": "3803395", "name": + "A. Sasson"}, {"authorId": "144926646", "name": "J. Fleming"}, {"authorId": + "4425897", "name": "J. Oliveto"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "11588674", "name": + "L. Berim"}, {"authorId": "144633198", "name": "P. Singh"}]}, {"paperId": + "d133cf7168dcd88b5ada3463782d53748df28203", "externalIds": {"MAG": "2582770688", + "DOI": "10.1016/j.jid.2017.01.013", "CorpusId": 11650426, "PubMed": "28143781"}, + "corpusId": 11650426, "publicationVenue": {"id": "6c1b0ec7-15b8-4f2e-8113-82a5eb121bde", + "name": "Journal of Investigative Dermatology", "type": "journal", "alternate_names": + ["J Investig Dermatol"], "issn": "0022-202X", "url": "http://www.blackwell-synergy.com/issuelist.asp?journal=jid", + "alternate_urls": ["https://www.jidonline.org/", "http://www.nature.com/jid/index.html"]}, + "url": "https://www.semanticscholar.org/paper/d133cf7168dcd88b5ada3463782d53748df28203", + "title": "Phenformin Enhances the Efficacy of ERK Inhibition in NF1-Mutant + Melanoma.", "abstract": null, "venue": "Journal of Investigative Dermatology", + "year": 2017, "referenceCount": 32, "citationCount": 23, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jidonline.org/article/S0022202X17300520/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2017-05-01", "journal": {"volume": + "137 5", "pages": "\n 1135-1143\n ", "name": "The Journal + of investigative dermatology"}, "authors": [{"authorId": "48333180", "name": + "S. Trousil"}, {"authorId": "2143502863", "name": "Shuang Chen"}, {"authorId": + "2144316440", "name": "Chan Mu"}, {"authorId": "49749587", "name": "F. Shaw"}, + {"authorId": "47845677", "name": "Z. Yao"}, {"authorId": "52133687", "name": + "Y. Ran"}, {"authorId": "94373231", "name": "T. Shakuntala"}, {"authorId": + "6949756", "name": "T. Merghoub"}, {"authorId": "5938253", "name": "D. Manstein"}, + {"authorId": "144020146", "name": "N. Rosen"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6765019", "name": "J. Zippin"}, {"authorId": + "143918840", "name": "B. Zheng"}]}, {"paperId": "d3a1522a6d4bdeb4ece083296badc729f718e163", + "externalIds": {"MAG": "2579698820", "DOI": "10.1021/acs.jmedchem.6b01166", + "CorpusId": 206619415, "PubMed": "28085281"}, "corpusId": 206619415, "publicationVenue": + {"id": "4cce60a8-2106-4240-bece-fb6488df6bd1", "name": "Journal of Medicinal + Chemistry", "type": "journal", "alternate_names": ["J Med Chem"], "issn": + "0022-2623", "url": "https://pubs.acs.org/journal/jmcmar", "alternate_urls": + ["http://pubs.acs.org/journal/jmcmar", "http://pubs.acs.org/journals/jmcmar/index.html"]}, + "url": "https://www.semanticscholar.org/paper/d3a1522a6d4bdeb4ece083296badc729f718e163", + "title": "\u03b1-Ketothioamide Derivatives: A Promising Tool to Interrogate + Phosphoglycerate Dehydrogenase (PHGDH).", "abstract": "Given the putative + role of PHGDH in cancer, development of inhibitors is required to explore + its function. In this context, we established and validated a straightforward + enzymatic assay suitable for high-throughput screening and we identified inhibitors + with similar chemical scaffolds. Through a convergent pharmacophore approach, + we synthesized \u03b1-ketothioamides that exhibit interesting in vitro PHGDH + inhibition and encouraging cellular results. These novel probes may be used + to understand the emerging biology of this metabolic target.", "venue": "Journal + of Medicinal Chemistry", "year": 2017, "referenceCount": 19, "citationCount": + 37, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc5603230?pdf=render", "status": + null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2017-01-27", "journal": {"volume": "60 4", "pages": "\n 1591-1597\n ", + "name": "Journal of medicinal chemistry"}, "authors": [{"authorId": "47476313", + "name": "S\u00e9verine Ravez"}, {"authorId": "5469111", "name": "C. Corbet"}, + {"authorId": "12674173", "name": "Quentin Spillier"}, {"authorId": "6205578", + "name": "A. Dutu"}, {"authorId": "13966444", "name": "A. Robin"}, {"authorId": + "6424987", "name": "Edouard Mullarky"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "2110687", "name": "O. Feron"}, {"authorId": "3317215", + "name": "R. Fr\u00e9d\u00e9rick"}]}, {"paperId": "d6d4fb1f4d953d83293c42671ea2f95071b964a9", + "externalIds": {"PubMedCentral": "5486569", "MAG": "2591971327", "DOI": "10.1007/s00432-017-2358-x", + "CorpusId": 25394724, "PubMed": "28247034"}, "corpusId": 25394724, "publicationVenue": + {"id": "6451604f-a8c1-487f-992d-af7cfbbeabed", "name": "Journal of Cancer + Research and Clinical Oncology", "type": "journal", "alternate_names": ["J + Cancer Res Clin Oncol"], "issn": "0171-5216", "url": "https://www.springer.com/medicine/oncology/journal/432", + "alternate_urls": ["https://link.springer.com/journal/432"]}, "url": "https://www.semanticscholar.org/paper/d6d4fb1f4d953d83293c42671ea2f95071b964a9", + "title": "Genomic characteristics of trastuzumab-resistant Her2-positive metastatic + breast cancer", "abstract": null, "venue": "Journal of Cancer Research and + Clinical Oncology", "year": 2017, "referenceCount": 33, "citationCount": 17, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc5486569?pdf=render", "status": null}, "fieldsOfStudy": + ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Medicine", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2017-02-28", "journal": {"volume": "143", "pages": "1255 - 1262", "name": + "Journal of Cancer Research and Clinical Oncology"}, "authors": [{"authorId": + "6096769", "name": "Mateus de Oliveira Taveira"}, {"authorId": "145834073", + "name": "S. Nabavi"}, {"authorId": "47906736", "name": "Yuker Wang"}, {"authorId": + "1815350", "name": "P. Tonellato"}, {"authorId": "46312487", "name": "F. Esteva"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "31554501", "name": + "G. Wulf"}]}, {"paperId": "e1ce6398d45f0d19b84a5da5333f957376bd343b", "externalIds": + {"MAG": "2607099952", "DOI": "10.1016/j.molcel.2017.04.001", "CorpusId": 453177, + "PubMed": "28431227"}, "corpusId": 453177, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/e1ce6398d45f0d19b84a5da5333f957376bd343b", + "title": "Membrane Lipids Speak to Histones.", "abstract": null, "venue": + "Molecules and Cells", "year": 2017, "referenceCount": 9, "citationCount": + 3, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.cell.com/article/S1097276517302319/pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2017-04-20", "journal": {"volume": "66 2", "pages": "\n 163-164\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "1723564", "name": "Yuxiang + Zheng"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "e59bdf9a74d240d4578adcd471571d30d56e476c", + "externalIds": {"MAG": "2666241239", "DOI": "10.1073/pnas.1704706114", "CorpusId": + 19050387, "PubMed": "28630349"}, "corpusId": 19050387, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/e59bdf9a74d240d4578adcd471571d30d56e476c", + "title": "PI3K-p110\u03b1 mediates the oncogenic activity induced by loss + of the novel tumor suppressor PI3K-p85\u03b1", "abstract": "Significance Phosphatidylinositol + 3-kinase (PI3K) pathway hyperactivation is a common event in cancer, and understanding + alterations in this pathway is critical. Recently, the p85 regulatory subunit + of PI3K has come into focus as a novel pathway component targeted in cancers. + We find that decreased p85\u03b1 contributes to transformation of in vitro + and in vivo models of breast cancer. We provide evidence that partial loss + of p85\u03b1 increases the binding of p110\u03b1\u2013p85 signaling complexes + to activated receptors, thereby augmenting PI3K pathway output. Our findings + indicate that p85\u03b1 loss may be transforming in any context where PI3K + is activated. Additionally, they implicate a role for monomeric free p85 as + a negative regulator of PI3K signaling. Mutation or loss of the p85 regulatory + subunit of phosphatidylinositol 3-kinase (PI3K) is emerging as a transforming + factor in cancer, but the mechanism of transformation has been controversial. + Here we find that hemizygous deletion of the PIK3R1 gene encoding p85\u03b1 + is a frequent event in breast cancer, with PIK3R1 expression significantly + reduced in breast tumors. PIK3R1 knockdown transforms human mammary epithelial + cells, and genetic ablation of Pik3r1 accelerates a mouse model of HER2/neu-driven + breast cancer. We demonstrate that partial loss of p85\u03b1 increases the + amount of p110\u03b1\u2013p85 heterodimers bound to active receptors, augmenting + PI3K signaling and oncogenic transformation. Pan-PI3K and p110\u03b1-selective + pharmacological inhibition effectively blocks transformation driven by partial + p85\u03b1 loss both in vitro and in vivo. Together, our data suggest that + p85\u03b1 plays a tumor-suppressive role in transformation, and suggest that + p110\u03b1-selective therapeutics may be effective in the treatment of breast + cancer patients with PIK3R1 loss.", "venue": "Proceedings of the National + Academy of Sciences", "year": 2017, "referenceCount": 40, "citationCount": + 60, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.pnas.org/content/pnas/114/27/7095.full.pdf", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2017-06-19", "journal": {"volume": "114", "pages": "7095 - 7100", "name": + "Proceedings of the National Academy of Sciences"}, "authors": [{"authorId": + "6190753", "name": "Lauren M Thorpe"}, {"authorId": "5217296", "name": "J. + Spangle"}, {"authorId": "38628965", "name": "Carolynn E Ohlson"}, {"authorId": + "7915457", "name": "Hailing Cheng"}, {"authorId": "6665338", "name": "T. Roberts"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "50985038", "name": + "Jean J. Zhao"}]}, {"paperId": "e6d3b06f311b70842adcfde49999f3c00bd1f0ca", + "externalIds": {"CorpusId": 35243054}, "corpusId": 35243054, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/e6d3b06f311b70842adcfde49999f3c00bd1f0ca", + "title": "PIK 3 CA C 2 domain deletions hyperactivate phosphoinositide 3-kinase + ( PI 3 K ) , generate oncogene dependence and are exquisitely sensitive to + PI 3 K\u03b1 inhibitors", "abstract": "Purpose: We describe herein a novel + P447_L455 deletion in the C2 domain of PIK3CA in a patient with an ER+ breast + cancer with an excellent response to the PI3K\u03b1 inhibitor alpelisib. Although + PIK3CA deletions are relatively rare, a significant portion of deletions cluster + within amino acids 446-460 of the C2 domain, suggesting these residues are + critical for p110\u03b1 function. Design: A computational structural model + of PIK3CA in complex with the p85 regulatory subunit and MCF10A cells expressing + PIK3CA and PIK3CA were used to understand the phenotype of C2 domain deletions. + Results: Computational modeling revealed specific favorable inter-residue + contacts that would be lost as a result of the deletion, predicting a significant + decrease in binding energy. Co-immunoprecipitation experiments showed reduced + binding of the C2 Research. on December 30, 2017. \u00a9 2017 American Association + for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts + have been peer reviewed and accepted for publication but have not yet been + edited. Author Manuscript Published OnlineFirst on December 28, 2017; DOI: + 10.1158/1078-0432.CCR-17-2141", "venue": "", "year": 2017, "referenceCount": + 27, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review"], "publicationDate": + null, "journal": null, "authors": [{"authorId": "5404128", "name": "Sarah + Croessmann"}, {"authorId": "6251014", "name": "J. Sheehan"}, {"authorId": + "46542827", "name": "Kyung-Min Lee"}, {"authorId": "3381467", "name": "Gregory + Sliwoski"}, {"authorId": "50774890", "name": "Ji\u00e9 He"}, {"authorId": + "39540895", "name": "R. Nagy"}, {"authorId": "82059310", "name": "David A. + Riddle"}, {"authorId": "2346140", "name": "I. Mayer"}, {"authorId": "66935619", + "name": "J. Balko"}, {"authorId": "3484938", "name": "R. Lanman"}, {"authorId": + "2134288", "name": "V. Miller"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1754226", "name": "J. Meiler"}, {"authorId": "2057460", "name": + "C. Arteaga"}]}, {"paperId": "ed2f419136e0df8b9ba01ce6784e40a7b561824e", "externalIds": + {"MAG": "2592811353", "DOI": "10.1158/2159-8290.CD-16-0778", "CorpusId": 4500636, + "PubMed": "28274958"}, "corpusId": 4500636, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/ed2f419136e0df8b9ba01ce6784e40a7b561824e", + "title": "Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating + Antitumor Innate Immunity.", "abstract": "Several kinase inhibitors that target + aberrant signaling pathways in tumor cells have been deployed in cancer therapy. + However, their impact on the tumor immune microenvironment remains poorly + understood. The tyrosine kinase inhibitor cabozantinib showed striking responses + in cancer clinical trial patients across several malignancies. Here, we show + that cabozantinib rapidly eradicates invasive, poorly differentiated PTEN/p53-deficient + murine prostate cancer. This was associated with enhanced release of neutrophil + chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting + in robust infiltration of neutrophils into the tumor. Critically, cabozantinib-induced + tumor clearance in mice was abolished by antibody-mediated granulocyte depletion + or HMGB1 neutralization or blockade of neutrophil chemotaxis with the CXCR4 + inhibitor plerixafor. Collectively, these data demonstrate that cabozantinib + triggers a neutrophil-mediated anticancer innate immune response, resulting + in tumor clearance.Significance: This study is the first to demonstrate that + a tyrosine kinase inhibitor can activate neutrophil-mediated antitumor innate + immunity, resulting in invasive cancer clearance. Cancer Discov; 7(7); 750-65. + \u00a92017 AACR.This article is highlighted in the In This Issue feature, + p. 653.", "venue": "Cancer Discovery", "year": 2017, "referenceCount": 54, + "citationCount": 88, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc5501767?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}, {"category": "Medicine", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2017-03-08", "journal": {"volume": "7 7", "pages": "\n 750-765\n ", + "name": "Cancer discovery"}, "authors": [{"authorId": "40501341", "name": + "A. Patnaik"}, {"authorId": "6784962", "name": "K. Swanson"}, {"authorId": + "4793517", "name": "E. Csizmadia"}, {"authorId": "39787428", "name": "Aniruddh + Solanki"}, {"authorId": "1417572171", "name": "Natalie Landon-Brace"}, {"authorId": + "33820964", "name": "M. Gehring"}, {"authorId": "49804844", "name": "Katja + Helenius"}, {"authorId": "21582882", "name": "Brian M Olson"}, {"authorId": + "15061933", "name": "A. Pyzer"}, {"authorId": "2117931332", "name": "Lily + C. Wang"}, {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": + "50577147", "name": "Jesse S. Novak"}, {"authorId": "4374091", "name": "T. + Thornley"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "49666064", + "name": "L. Montaser"}, {"authorId": "6571591", "name": "J. Timmons"}, {"authorId": + "74997355", "name": "T. Morgan"}, {"authorId": "49416325", "name": "Yugang + Wang"}, {"authorId": "3768843", "name": "E. Levantini"}, {"authorId": "4102988", + "name": "J. Clohessy"}, {"authorId": "145953924", "name": "K. Kelly"}, {"authorId": + "4499580", "name": "P. Pandolfi"}, {"authorId": "31499217", "name": "J. Rosenblatt"}, + {"authorId": "145881219", "name": "D. Avigan"}, {"authorId": "3073381", "name": + "Huihui Ye"}, {"authorId": "5747025", "name": "J. Karp"}, {"authorId": "7505152", + "name": "S. Signoretti"}, {"authorId": "6189162", "name": "S. Balk"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "f67131dcb58de600f5f0bbf972fd4ae4c2f07098", + "externalIds": {"MAG": "2735063286", "DOI": "10.1016/j.ccell.2017.06.004", + "CorpusId": 3692828, "PubMed": "28697344"}, "corpusId": 3692828, "publicationVenue": + {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", "name": "Cancer Cell", "type": + "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/f67131dcb58de600f5f0bbf972fd4ae4c2f07098", + "title": "MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose + Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer.", "abstract": + null, "venue": "Cancer Cell", "year": 2017, "referenceCount": 50, "citationCount": + 219, "influentialCitationCount": 4, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1535610817302544/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2017-07-10", "journal": {"volume": "32 1", "pages": "\n 71-87.e7\n ", + "name": "Cancer cell"}, "authors": [{"authorId": "5313024", "name": "S. Shukla"}, + {"authorId": "40401242", "name": "V. Purohit"}, {"authorId": "6262895", "name": + "Kamiya Mehla"}, {"authorId": "3474931", "name": "V. Gunda"}, {"authorId": + "12164048", "name": "Nina V. Chaika"}, {"authorId": "4197522", "name": "E. + Vernucci"}, {"authorId": "14809253", "name": "Ryan J. King"}, {"authorId": + "6519716", "name": "J. Abrego"}, {"authorId": "40498919", "name": "G. Goode"}, + {"authorId": "4198255", "name": "Aneesha Dasgupta"}, {"authorId": "19371882", + "name": "Alysha L. Illies"}, {"authorId": "50019590", "name": "T. Gebregiworgis"}, + {"authorId": "39746276", "name": "B. Dai"}, {"authorId": "47024265", "name": + "Jithesh J. Augustine"}, {"authorId": "48665899", "name": "Divya Murthy"}, + {"authorId": "12496228", "name": "K. Attri"}, {"authorId": "13470228", "name": + "Oksana Mashadova"}, {"authorId": "6621353", "name": "P. Grandgenett"}, {"authorId": + "145461840", "name": "R. Powers"}, {"authorId": "14222342", "name": "Q. Ly"}, + {"authorId": "3652387", "name": "A. Lazenby"}, {"authorId": "4068345", "name": + "J. Grem"}, {"authorId": "145120646", "name": "F. Yu"}, {"authorId": "35070687", + "name": "J. Mat\u00e9s"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "2110045806", "name": "Jung-whan Kim"}, {"authorId": "5866146", "name": "J. + Hankins"}, {"authorId": "143872276", "name": "C. Weekes"}, {"authorId": "38154576", + "name": "M. Hollingsworth"}, {"authorId": "6361174", "name": "N. Serkova"}, + {"authorId": "3803395", "name": "A. Sasson"}, {"authorId": "144926646", "name": + "J. Fleming"}, {"authorId": "4425897", "name": "J. Oliveto"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "11588674", "name": "L. Berim"}, {"authorId": "144633198", "name": + "P. Singh"}]}, {"paperId": "01f49fa909cb1c8fa044e948388d6d9796580776", "externalIds": + {"MAG": "2442812297", "DOI": "10.1073/pnas.1600934113", "CorpusId": 11852213, + "PubMed": "27313209"}, "corpusId": 11852213, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/01f49fa909cb1c8fa044e948388d6d9796580776", + "title": "Deletion of the gene Pip4k2c, a novel phosphatidylinositol kinase, + results in hyperactivation of the immune system", "abstract": "Significance + The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway is + an important facet of the immune system, including that it regulates T-cell + differentiation and activation. Here, we report that type 2 phosphatidylinositol-5-phosphate + 4-kinase gamma (protein, PI5P4K\u03b3; gene, PIP4K2C) plays a role in the + regulation of the immune system by manipulating mTORC1 signaling. These results + suggest that the SNP at the PIP4K2C locus (rs1678542) in human patients with + autoimmunity might cause a decrease in PI5P4K\u03b3 expression and thereby + an increase in mTORC1 signaling. In addition, these results imply that inhibition + of mTORC1 would be beneficial to these patients. These studies also suggest + that agents that inhibit PIP4K2C function could be useful to enhance cancer + immunotherapy. Type 2 phosphatidylinositol-5-phosphate 4-kinase (PI5P4K) converts + phosphatidylinositol-5-phosphate to phosphatidylinositol-4,5-bisphosphate. + Mammals have three enzymes PI5P4K\u03b1, PI5P4K\u03b2, and PI5P4K\u03b3, and + these enzymes have been implicated in metabolic control, growth control, and + a variety of stress responses. Here, we show that mice with germline deletion + of type 2 phosphatidylinositol-5-phosphate 4-kinase gamma (Pip4k2c), the gene + encoding PI5P4K\u03b3, appear normal in regard to growth and viability but + have increased inflammation and T-cell activation as they age. Immune cell + infiltrates increased in Pip4k2c\u2212/\u2212 mouse tissues. Also, there was + an increase in proinflammatory cytokines, including IFN\u03b3, interleukin + 12, and interleukin 2 in plasma of Pip4k2c\u2212/\u2212 mice. Pip4k2c\u2212/\u2212 + mice had an increase in T-helper-cell populations and a decrease in regulatory + T-cell populations with increased proliferation of T cells. Interestingly, + mammalian target of rapamycin complex 1 (mTORC1) signaling was hyperactivated + in several tissues from Pip4k2c\u2212/\u2212 mice and treating Pip4k2c\u2212/\u2212 + mice with rapamycin reduced the inflammatory phenotype, resulting in a decrease + in mTORC1 signaling in tissues and a decrease in proinflammatory cytokines + in plasma. These results indicate that PI5P4K\u03b3 plays a role in the regulation + of the immune system via mTORC1 signaling.", "venue": "Proceedings of the + National Academy of Sciences", "year": 2016, "referenceCount": 22, "citationCount": + 43, "influentialCitationCount": 4, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.pnas.org/content/pnas/113/27/7596.full.pdf", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2016-06-16", "journal": {"volume": "113", "pages": "7596 + - 7601", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "13574443", "name": "Hyeseok Shim"}, {"authorId": "46740724", + "name": "Chuan Wu"}, {"authorId": "14390729", "name": "Shivan Ramsamooj"}, + {"authorId": "7881810", "name": "Kaitlyn Bosch"}, {"authorId": "153267992", + "name": "Zuojia Chen"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "40164091", "name": "Jihye Yun"}, {"authorId": "2146671919", "name": "Hui + Liu"}, {"authorId": "1401641678", "name": "R. Choo-Wing"}, {"authorId": "50109290", + "name": "Zhiwei Yang"}, {"authorId": "31554501", "name": "G. Wulf"}, {"authorId": + "4401436", "name": "V. Kuchroo"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "0a400c6b377db169d75fa10d9018c1fdc628b62f", "externalIds": {"MAG": + "2266570683", "DOI": "10.1073/pnas.1521548113", "CorpusId": 52852929, "PubMed": + "26831078"}, "corpusId": 52852929, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/0a400c6b377db169d75fa10d9018c1fdc628b62f", + "title": "Identification of a small molecule inhibitor of 3-phosphoglycerate + dehydrogenase to target serine biosynthesis in cancers", "abstract": "Significance + Serine supports a number of anabolic processes, including protein, lipid, + and nucleic acid synthesis. Cells can either import serine or synthesize it + de novo. Recently, overexpression of 3-phosphoglycerate dehydrogenase (PHGDH), + the gene encoding the first committed step of serine synthesis, via focal + amplification and other mechanisms, has been identified in human cancers. + Cancer cell lines that overexpress PHGDH are uniquely sensitive to PHGDH knockdown + whereas lines that express little PHGDH are insensitive, suggesting that PHGDH + may be a clinically interesting target. Here, we report the discovery of a + specific small molecule inhibitor of PHGDH, which enables preclinical evaluation + of PHGDH as a target in cancer and provides a tool to study the biology of + de novo serine synthesis. Cancer cells reprogram their metabolism to promote + growth and proliferation. The genetic evidence pointing to the importance + of the amino acid serine in tumorigenesis is striking. The gene encoding the + enzyme 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first + committed step of serine biosynthesis, is overexpressed in tumors and cancer + cell lines via focal amplification and nuclear factor erythroid-2-related + factor 2 (NRF2)-mediated up-regulation. PHGDH-overexpressing cells are exquisitely + sensitive to genetic ablation of the pathway. Here, we report the discovery + of a selective small molecule inhibitor of PHGDH, CBR-5884, identified by + screening a library of 800,000 drug-like compounds. CBR-5884 inhibited de + novo serine synthesis in cancer cells and was selectively toxic to cancer + cell lines with high serine biosynthetic activity. Biochemical characterization + of the inhibitor revealed that it was a noncompetitive inhibitor that showed + a time-dependent onset of inhibition and disrupted the oligomerization state + of PHGDH. The identification of a small molecule inhibitor of PHGDH not only + enables thorough preclinical evaluation of PHGDH as a target in cancers, but + also provides a tool with which to study serine metabolism.", "venue": "Proceedings + of the National Academy of Sciences", "year": 2016, "referenceCount": 81, + "citationCount": 184, "influentialCitationCount": 11, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/113/7/1778.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2016-02-01", "journal": {"volume": "113", "pages": "1778 + - 1783", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": "6490745", + "name": "N. Lucki"}, {"authorId": "8280749", "name": "Reza B. Beheshti Zavareh"}, + {"authorId": "35906509", "name": "J. Anglin"}, {"authorId": "2087116099", + "name": "Ana P Gomes"}, {"authorId": "4374034", "name": "Brandon Nicolay"}, + {"authorId": "40497062", "name": "Jenny C. Y. Wong"}, {"authorId": "32173727", + "name": "S. Christen"}, {"authorId": "2115843581", "name": "Hidenori Takahashi"}, + {"authorId": "2109204398", "name": "P. Singh"}, {"authorId": "4037343", "name": + "J. Blenis"}, {"authorId": "32988325", "name": "J. Warren"}, {"authorId": + "46775302", "name": "S. Fendt"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "4772111", "name": "G. DeNicola"}, {"authorId": "4901222", "name": + "C. Lyssiotis"}, {"authorId": "6627833", "name": "L. Lairson"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "0b0f7ff147e42ca79bbaa7763d1759dd5eaee1da", + "externalIds": {"MAG": "2319881581", "DOI": "10.1038/ng0329-473a", "CorpusId": + 8524302, "PubMed": "27023779"}, "corpusId": 8524302, "publicationVenue": {"id": + "bb27e645-e57c-42c3-bcbc-c7b443c58209", "name": "Nature Genetics", "type": + "journal", "alternate_names": ["Nat Genet"], "issn": "1061-4036", "url": "http://www.nature.com/ng/", + "alternate_urls": ["http://www.nature.com/ng/index.html"]}, "url": "https://www.semanticscholar.org/paper/0b0f7ff147e42ca79bbaa7763d1759dd5eaee1da", + "title": "Erratum: NRF2 regulates serine biosynthesis in non\u2013small cell + lung cancer", "abstract": null, "venue": "Nature Genetics", "year": 2016, + "referenceCount": 1, "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://www.nature.com/articles/ng0329-473a.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2016-04-01", "journal": {"volume": "48", "pages": + "473-473", "name": "Nature Genetics"}, "authors": [{"authorId": "4772111", + "name": "G. DeNicola"}, {"authorId": "4047142", "name": "Pei-Hsuan Chen"}, + {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": "5467431", + "name": "J. Sudderth"}, {"authorId": "3616375", "name": "Zeping Hu"}, {"authorId": + "144790190", "name": "David Wu"}, {"authorId": "2112388600", "name": "Hao + Tang"}, {"authorId": "145668114", "name": "Yang Xie"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "5305256", "name": "K. Huffman"}, {"authorId": + "46528860", "name": "I. Wistuba"}, {"authorId": "2996220", "name": "J. Minna"}, + {"authorId": "5834413", "name": "R. Deberardinis"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "24021285521e5d21fe2a2fb7f58254186ad1d7e9", + "externalIds": {"MAG": "2494704798", "DOI": "10.1158/1538-7445.AM2016-1625", + "CorpusId": 78226268}, "corpusId": 78226268, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/24021285521e5d21fe2a2fb7f58254186ad1d7e9", + "title": "Abstract 1625: CUB domain-containing protein 1 (CDCP1) promotes + metastatic phenotype in pancreatic ductal adenocarcinoma", "abstract": null, + "venue": "", "year": 2016, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2016-07-15", "journal": {"volume": "76", "pages": "1625-1625", "name": "Cancer + Research"}, "authors": [{"authorId": "2109648661", "name": "Sunnie S. Kim"}, + {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": "48821307", "name": + "B. Hopkins"}, {"authorId": "31875049", "name": "Ryan Loughran"}, {"authorId": + "82902019", "name": "S. Naranjos"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "27ef47762fd0715155c952a9bb89b018ecff9acd", "externalIds": {"MAG": + "2474366905", "DOI": "10.1073/pnas.1522223113", "CorpusId": 20555480, "PubMed": + "27402769"}, "corpusId": 20555480, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/27ef47762fd0715155c952a9bb89b018ecff9acd", + "title": "Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside + depletion", "abstract": "Significance Mutations in the PI3K pathway are highly + prevalent in cancers, and isoform-specific and pan-PI3K inhibitors have entered + clinical trials in both solid and hematologic malignancies. The PI3K \u03b4-specific + inhibitor idelalisib (in combination with rituximab) was recently approved + for the treatment of chronic lymphocytic leukemia. However, identifying tumor + types and biological mechanisms that predict for response to PI3K inhibitors + as single agents or in combination has been a challenge. Our data indicate + that PI3K inhibitors induce DNA damage in tumors that have defects in DNA + damage-repair pathways and that they do so by impairing the production of + Rib phosphate and amino acids needed for deoxynucleotide synthesis. We previously + reported that combining a phosphoinositide 3-kinase (PI3K) inhibitor with + a poly-ADP Rib polymerase (PARP)-inhibitor enhanced DNA damage and cell death + in breast cancers that have genetic aberrations in BRCA1 and TP53. Here, we + show that enhanced DNA damage induced by PI3K inhibitors in this mutational + background is a consequence of impaired production of nucleotides needed for + DNA synthesis and DNA repair. Inhibition of PI3K causes a reduction in all + four nucleotide triphosphates, whereas inhibition of the protein kinase AKT + is less effective than inhibition of PI3K in suppressing nucleotide synthesis + and inducing DNA damage. Carbon flux studies reveal that PI3K inhibition disproportionately + affects the nonoxidative pentose phosphate pathway that delivers Rib-5-phosphate + required for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative + breast cancer (K14-Cre BRCA1f/fp53f/f), the PI3K inhibitor BKM120 led to a + precipitous drop in DNA synthesis within 8 h of drug treatment, whereas DNA + synthesis in normal tissues was less affected. In this mouse model, combined + PI3K and PARP inhibition was superior to either agent alone to induce durable + remissions of established tumors.", "venue": "Proceedings of the National + Academy of Sciences", "year": 2016, "referenceCount": 41, "citationCount": + 66, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc4968752?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2016-07-08", "journal": {"volume": "113", "pages": "E4338 - E4347", "name": + "Proceedings of the National Academy of Sciences"}, "authors": [{"authorId": + "49149990", "name": "Ashish Juvekar"}, {"authorId": "113164867", "name": "Hai + Hu"}, {"authorId": "3893473", "name": "S. Yadegarynia"}, {"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "50136879", "name": "Soumya Ullas"}, + {"authorId": "4729701", "name": "Evan C. Lien"}, {"authorId": "5679020", "name": + "G. Bellinger"}, {"authorId": "38313825", "name": "J. Son"}, {"authorId": + "11228582", "name": "R. Hok"}, {"authorId": "143667851", "name": "P. Seth"}, + {"authorId": "49947506", "name": "M. B. Daly"}, {"authorId": "2144570709", + "name": "Baek Kim"}, {"authorId": "143905392", "name": "R. Scully"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "31554501", "name": "G. Wulf"}]}, {"paperId": "2f2ee38e6b78d20cf997cbcb0a7e724d6d755937", + "externalIds": {"MAG": "2562883911", "DOI": "10.5772/65141", "CorpusId": 4690688}, + "corpusId": 4690688, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/2f2ee38e6b78d20cf997cbcb0a7e724d6d755937", + "title": "NRF2 Rewires Cellular Metabolism to Support the Antioxidant Response", + "abstract": "The transcription factor (nuclear factor-erythroid 2 p45-related + factor 2, NRF2) is a master regulator of the cellular response to oxidative + insults. While antioxidant response enzymes are well-characterized transcriptional + targets of NRF2, it is recently becoming clear that NRF2 also supports cellular + detoxification through metabolic rewiring to support the antioxidant systems. + In this chapter, we discuss the regulation of NRF2 and how NRF2 activation + promotes the antioxidant defense of cells. Further-more, we discuss how reactive + oxygen species influence cellular metabolism and how this affects antioxidant + function. We also discuss how NRF2 reprograms cellular metabolism to support + the antioxidant response and how this functions to funnel metabolic intermediates + into antioxidant pathways. This chapter concludes by exploring how these factors + may contribute to both normal physiology and disease. transports cystine into + the cell which is reduced to cysteine via TXNRD, and glutamate is generated + by glutaminase 1 (GLS1) and GLS2 using glutamine as a substrate. Furthermore, + xenobiotics undergo oxidation, reduction, or hydrolysis by cytochrome P450 + enzymes and are subsequently conjugated with glucuronic acid, catalyzed by + UDP-glucuronosyltransferase (UGT), and exported out of the cells by multidrug + resistance-associated proteins (MRP). Some of the xenobiotics such as quinones + can undergo redox cycling which results in ROS production, which is counteracted + by the NADPH-required reduction reactions catalyzed by aldo-keto reductase + (AKR) and NAD(P)H: quinone oxidoreductase 1 (NQO1). The role of NRF2 in mediating + the antioxidant response is through (1) regulation of NADPH-generating enzymes + (G6PD, PGD, IDH1, and ME1); (2) upregulation of the enzymes required for GSH + production, regeneration, and utilization, such as GLS1/GLS2 and GCLM/GCLC; + (3) regulation of XCT to increase the intracellular cysteine pool in support + of GSH synthesis; and (4) upregulation of UDP-glucuronosyltransferase (UGT) + to promote glucuronidation pathway. \u03b1-KG dehydrogenase complex. Succinyl-CoA + is then trans-formed to succinate by the succinyl-CoA synthetase. is oxidized + to fumarate the succinate dehydrogenase (SDH) complex and hydrated to malate + by fumarate hydratase (FH). Oxidation of malate, catalyzed by malate dehydrogenase, + finally regenerates oxaloacetate, and the cycle continues.", "venue": "", + "year": 2016, "referenceCount": 134, "citationCount": 24, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.intechopen.com/citation-pdf-url/52298", + "status": null}, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-12-21", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "144181325", "name": "Ting-Yu Lin"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4772111", "name": + "G. DeNicola"}]}, {"paperId": "34b188d2d5ab1d0e50b32245654c9c091735ca27", + "externalIds": {"MAG": "2509166389", "DOI": "10.1073/pnas.1606862113", "CorpusId": + 27171538, "PubMed": "27528663"}, "corpusId": 27171538, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/34b188d2d5ab1d0e50b32245654c9c091735ca27", + "title": "Mitotic MELK-eIF4B signaling controls protein synthesis and tumor + cell survival", "abstract": "Significance The work identifies the eukaryotic + translation initiation factor 4B (eIF4B) as a substrate of maternal and embryonic + leucine zipper kinase (MELK), a mitotic kinase known to be essential for aggressive + types of malignancy. The MELK\u2013eIF4B axis thus represents a previously + unidentified signaling pathway that regulates protein synthesis during mitosis + and, consequently, the survival of cancer cells. The protein kinase maternal + and embryonic leucine zipper kinase (MELK) is critical for mitotic progression + of cancer cells; however, its mechanisms of action remain largely unknown. + By combined approaches of immunoprecipitation/mass spectrometry and peptide + library profiling, we identified the eukaryotic translation initiation factor + 4B (eIF4B) as a MELK-interacting protein during mitosis and a bona fide substrate + of MELK. MELK phosphorylates eIF4B at Ser406, a modification found to be most + robust in the mitotic phase of the cell cycle. We further show that the MELK\u2013eIF4B + signaling axis regulates protein synthesis during mitosis. Specifically, synthesis + of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play + a role in cancer cell survival during cell division, depends on the function + of MELK-elF4B. Inactivation of MELK or eIF4B results in reduced protein synthesis + of MCL1, which, in turn, induces apoptotic cell death of cancer cells. Our + study thus defines a MELK\u2013eIF4B signaling axis that regulates protein + synthesis during mitosis, and consequently influences cancer cell survival.", + "venue": "Proceedings of the National Academy of Sciences", "year": 2016, + "referenceCount": 35, "citationCount": 54, "influentialCitationCount": 4, + "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/113/35/9810.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2016-08-15", "journal": {"volume": + "113", "pages": "9810 - 9815", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "2145192690", "name": "Yubao Wang"}, + {"authorId": "69874482", "name": "M. Begley"}, {"authorId": "2117896212", + "name": "Qing Li"}, {"authorId": "1901277", "name": "Hai-Tsang Huang"}, {"authorId": + "3931691", "name": "Ana Lako"}, {"authorId": "2026802", "name": "M. Eck"}, + {"authorId": "3977406", "name": "N. Gray"}, {"authorId": "4294579", "name": + "T. Mitchison"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "50985038", "name": "Jean J. Zhao"}]}, {"paperId": "467a4bb63f210a0b4aa31be9ac37889dbddb370c", + "externalIds": {"MAG": "2511352587", "CorpusId": 89555904}, "corpusId": 89555904, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/467a4bb63f210a0b4aa31be9ac37889dbddb370c", + "title": "Increased insulin sensitivity i subunit of phosphoinositide", "abstract": + "On the basis of ex vivo studies using insulin-responsive cells, d( activation + of a Class IA phosphoinositide 3-kinase (P13K) seems to pi be required for + a wide variety of cellular responses downstream of st insulin. The Class IA + P13K enzymes are heterodimers of catalytic and ai regulatory subunits. In + mammals, insulin-responsive tissues ex- o0 press both the p85a and p8513 isoforms + of the regulatory subunit. ul Surprisingly, recent studies have revealed that + disruption of the p; p85a gene in the mouse (p85a-/- mice) results in hypoglycemia + bi with decreased plasma insulin, and the p85a''+- mice exhibit significantly + increased insulin sensitivity. These results suggest re either that p85a negatively + regulates insulin signaling, or that ac p85P, which mediates the major fraction + of Class IA P13K signaling pi in the absence of p85a, is more efficient than + p85a in mediating Ir insulin responses. To address this question, we have + generated vi mice in which the p8513 gene is deleted (p8581-''- mice). As + with the b'' p85a-/- mice, the p8513-/- mice showed hypoinsulinemia, hypo- + a( glycemia, and improved insulin sensitivity. At the molecular level, e2 + P13K activity associated with phosphotyrosine complexes was P1 preserved despite + a 20-30% reduction in the total protein level of e) the regulatory subunits. + Moreover, insulin-induced activation of PI AKT was significantly up-regulated + in muscle from the p85p3-- cl mice. In addition, insulin-dependent tyrosine + phosphorylation of P'' insulin receptor substrate-2 was enhanced in the p85,18-- + mice, a 1phenotype not observed in the p85a-''- mice. These results indi- + th cate that in addition to their roles in recruiting the catalytic subunit + Vi of P13K to the insulin receptor substrate proteins, both p85a and o0 p8513 + play negative roles in insulin signaling. (2 ot Insulin activates Class IA + phosphoinositide 3-kinase (PI3K) to (", "venue": "", "year": 2016, "referenceCount": + 6, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "", "name": ""}, "authors": + [{"authorId": "5177377", "name": "K. Ueki"}, {"authorId": "88813773", "name": + "Claudine M. Yballett"}, {"authorId": "3710358", "name": "S. Brachmann"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "9928532", "name": + "D. Vicent"}, {"authorId": "40474206", "name": "J. Watt"}, {"authorId": "144391716", + "name": "C. Kahn"}]}, {"paperId": "469a6c1e14f7a29729a558c5ea715d1c3b1d65f9", + "externalIds": {"MAG": "2400332577", "DOI": "10.1158/1538-7445.SABCS15-P3-07-41", + "CorpusId": 76803133}, "corpusId": 76803133, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/469a6c1e14f7a29729a558c5ea715d1c3b1d65f9", + "title": "Abstract P3-07-41: Genomic alterations indicative of a luminal A + subtype associate with clinical benefit to buparlisib and letrozole in endocrine-resistant + ER+/HER2\u2013 metastatic breast cancer", "abstract": "Background: Activation + of the phosphoinositide-3-kinase (PI3K) pathway has been associated with resistance + to endocrine therapy in estrogen receptor-positive (ER+) breast cancer. Recently, + we reported a Stand Up 2 Cancer (SU2C) Phase Ib trial of buparlisib, an oral, + reversible, pan-PI3K inhibitor in combination with the aromatase inhibitor + letrozole in patients with metastatic ER+/HER2\u2013 breast cancer (n=51) + who had previously progressed on endocrine therapy. In this study, 31% of + patients demonstrated clinical benefit (CR, PR and SD \u22656 months; Mayer + et al. JCO 2014). Clinical activity was observed in patients with PIK3CA-wild + type (PIK3CA-WT) and PIK3CA-mutant (PIK3CA-MUT) tumors. We performed targeted + next-generation sequencing (tNGS) to identify somatic alterations associated + with clinical benefit to the combination therapy. Methods: tNGS was performed + using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable + Cancer Targets (MSK-IMPACT) in DNA extracted from tumors of 33 study patients + (22 samples from archived primary/untreated and 11 from metastatic biopsies). + Detected alterations were tested for association with clinical benefit (Fisher9s + exact test) and progression-free survival (PFS; log-rank test). For PFS analysis, + patients were censored if they discontinued buparlisib for toxicity. Results: + The most commonly detected alterations occurred in PIK3CA (36%), TP53 (30%), + MAP3K1 (27%), GATA3 (24%), CCND1 (24%), CDH1 (21%) and PTEN (21%). Additional + alterations of note included FGFR1 amplification (15%), MYC amplification + (12%), ESR1 mutations (6%) and ERBB2 mutations (6%). Probable inactivating + mutations occurring in MAP3K1 (MAP3K1-MUT) were significantly associated with + improved clinical benefit, regardless of other mutations (6/9 patients, 67%, + P=0.044). PIK3CA-MUT tumors trended toward greater clinical benefit (7/12, + 58%, P=0.067). Patients with coexisting PIK3CA-MUT and MAP3K1-MUT tumors derived + the largest clinical benefit (5/7, 70% P=0.07) compared to patients with only + PIK3CA-MUT (2/5; 40%, P=1.0) or only MAP3K1-MUT tumors (1/2; 50%, P=1.0). + Only 2/19 (11%) patients with PIK3CA-WT/MAP3K1-WT cancers benefitted from + treatment. Both MAP3K1 and PIK3CA alterations were each also associated with + increased PFS (p=0.03 and p=0.009, respectively). Three of 5 (60%) patients + with tumors with FGFR1 amplification achieved clinical benefit (including + a MAP3K1-MUT tumor and a PIK3CA-MUT/MAP3K1-MUT tumor), suggesting that FGFR1 + may preferentially signal via PI3K and/or FGFR1 amplifications are not associated + with resistance to the combination of aromatase inhibitors and PI3K inhibitors. + Conclusions: Both MAP3K1 and PIK3CA are mutated at higher frequencies in luminal + A breast cancer, suggesting that this alteration pattern (MAP3K1-MUT + PIK3CA-MUT) + is a surrogate for low grade ER+ breast cancers with PI3K dependence. It is + also possible that MAP3K1 mutations may predispose tumor cells to sensitivity + to PI3K inhibition, but this speculation requires further investigation. Finally, + patients with ER+/FGFR1-amplified cancers appeared to derive clinical benefit + from combined therapy with letrozole and buparlisib. Citation Format: Balko + JM, Hicks M, Berger MF, Solit DB, Bouvier N, Sanders ME, Estrada MV, Won H, + Cantley LC, Mayer IA, Arteaga CL. Genomic alterations indicative of a luminal + A subtype associate with clinical benefit to buparlisib and letrozole in endocrine-resistant + ER+/HER2\u2013 metastatic breast cancer. [abstract]. In: Proceedings of the + Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec + 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract + nr P3-07-41.", "venue": "", "year": 2016, "referenceCount": 0, "citationCount": + 2, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2016-02-15", "journal": {"volume": "76", "name": "Cancer + Research"}, "authors": [{"authorId": "66935619", "name": "J. Balko"}, {"authorId": + "47040859", "name": "Mellissa J. Hicks"}, {"authorId": "33727638", "name": + "M. Berger"}, {"authorId": "2344124", "name": "D. Solit"}, {"authorId": "5285964", + "name": "N. Bouvier"}, {"authorId": "46945931", "name": "M. Sanders"}, {"authorId": + "144820856", "name": "M. V. Estrada"}, {"authorId": "3738649", "name": "H. + Won"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2346140", + "name": "I. Mayer"}, {"authorId": "145739236", "name": "C. Arteaga"}]}, {"paperId": + "4dada490702a33d684142edbfb44790b36903dc9", "externalIds": {"MAG": "2561471811", + "DOI": "10.1093/annonc/mdw672", "CorpusId": 3784120, "PubMed": "27993796"}, + "corpusId": 3784120, "publicationVenue": {"id": "9777e708-5066-48fd-ab6a-57496cbca033", + "name": "Annals of Oncology", "type": "journal", "alternate_names": ["Ann + Oncol"], "issn": "0923-7534", "url": "https://academic.oup.com/annonc/issue", + "alternate_urls": ["http://annonc.oxfordjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/4dada490702a33d684142edbfb44790b36903dc9", + "title": "Phase I dose escalation study of the PI3kinase pathway inhibitor + BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib + for the treatment of high-grade serous ovarian and breast cancer", "abstract": + "Background Based upon preclinical synergy in murine models, we carried out + a phase I trial to determine the maximum tolerated dose (MTD), toxicities, + pharmacokinetics, and biomarkers of response for the combination of BKM120, + a PI3K inhibitor, and olaparib, a PARP inhibitor. Patients and methods Olaparib + was administered twice daily (tablet formulation) and BKM120 daily on a 28-day + cycle, both orally. A 3\u2009+\u20093 dose-escalation design was employed + with the primary objective of defining the combination MTD, and secondary + objectives were to define toxicities, activity, and pharmacokinetic profiles. + Eligibility included recurrent breast (BC) or ovarian cancer (OC); dose-expansion + cohorts at the MTD were enrolled for each cancer. Results In total, 69 of + 70 patients enrolled received study treatment; one patient never received + study treatment because of ineligibility. Twenty-four patients had BC; 46 + patients had OC. Thirty-five patients had a germline BRCA mutation (gBRCAm). + Two DLTs (grade 3 transaminitis and hyperglycemia) were observed at DL0 (BKM120 + 60\u2009mg/olaparib and 100\u2009mg b.i.d.). The MTD was determined to be + BKM120 50\u2009mg q.d. and olaparib 300\u2009mg b.i.d. (DL8). Additional DLTs + included grade 3 depression and transaminitis, occurring early in cycle 2 + (DL7). Anticancer activity was observed in BC and OC and in gBRCAm and gBRCA + wild-type (gBRCAwt) patients. Conclusions BKM120 and olaparib can be co-administered, + but the combination requires attenuation of the BKM120 dose. Clinical benefit + was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will + be needed to further define the efficacy of PI3K/PARP-inhibitor combinations + as compared with a PARP inhibitor alone.", "venue": "Annals of Oncology", + "year": 2016, "referenceCount": 20, "citationCount": 155, "influentialCitationCount": + 2, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "ClinicalTrial"], "publicationDate": "2016-12-19", "journal": {"volume": "28", + "pages": "&NA;", "name": "Annals of Oncology"}, "authors": [{"authorId": "6927295", + "name": "U. Matulonis"}, {"authorId": "31554501", "name": "G. Wulf"}, {"authorId": + "143997654", "name": "W. Barry"}, {"authorId": "2167106", "name": "M. Birrer"}, + {"authorId": "2974900", "name": "S. Westin"}, {"authorId": "7862178", "name": + "S. Farooq"}, {"authorId": "1397923721", "name": "K. Bell-McGuinn"}, {"authorId": + "12793341", "name": "E. Obermayer"}, {"authorId": "122974814", "name": "C. + Whalen"}, {"authorId": "15372310", "name": "T. Spagnoletti"}, {"authorId": + "4146119", "name": "W. Luo"}, {"authorId": "80370843", "name": "H. Liu"}, + {"authorId": "11228582", "name": "R. Hok"}, {"authorId": "6128162", "name": + "C. Aghajanian"}, {"authorId": "2344124", "name": "D. Solit"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "2069535097", "name": "B. S. + Taylor"}, {"authorId": "3738649", "name": "H. Won"}, {"authorId": "33727638", + "name": "M. Berger"}, {"authorId": "32453098", "name": "S. Palakurthi"}, {"authorId": + "48211579", "name": "J. Liu"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2369378", "name": "E. Winer"}]}, {"paperId": "50d95d9b96f4262d141d66a88f52f7d39ed5180b", + "externalIds": {"MAG": "2501520748", "DOI": "10.1158/1538-7445.AM2016-3858", + "CorpusId": 79095496}, "corpusId": 79095496, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/50d95d9b96f4262d141d66a88f52f7d39ed5180b", + "title": "Abstract 3858: Feasibility and efficacy of a precision treatment + approach for triple-negative breast cancer in mouse models", "abstract": "15-20% + of human breast tumors are triple negative breast cancer (TNBC), an aggressive + and deadly subtype of breast cancer that currently lack targeted therapies, + leaving chemotherapy as the only systemic treatment option. There is a pressing + need for a better understanding of disease mechanisms of TNBC, and for the + development of new treatment options. While activating mutations of PIK3CA + are frequently found in ER-positive and Her2-amplified breast cancer, inactivation + of lipid phosphatases is more frequent in TNBC. Analysis of large human genomics + data in TCGA reveals that heterozygous-loss of INPP4B, a lipid phosphates + in the PI3K signaling pathway, is enriched in TNBC subtype, and strongly correlates + with loss of ER expression. Guided by human genomics information, we have + crossed INPP4B phosphatase deletion mice into TNBC mouse model to determine + whether INPP4B-loss cooperates with loss-of-function of p53 and/or Brca1 to + promote tumorigenesis in vivo. Our results show dose-dependent increase in + tumor development frequency in K14cre; Brca1flox/flox; p53flox/flox mice carrying + INPP4B Phosphatase KO allele, HET allele compared to INPP4B WT allele. Importantly, + these tumors resemble human TNBC in their pathology, histological patterns + and gene expression patterns, providing a valuable platform to test their + responsiveness to various therapeutic drugs, including PI3K-inhibitors. Our + goal is to generate data that form the basis for a phase I/II clinical study + that lead to substantially improved treatment strategies for basal-like breast + cancer. Toward this goal, we have banked the endogenous tumors in a way allowing + transplantation in nude mice, and have performed randomized drug treatment + studies. We found that tumors that are heterozygous or deletion for INPP4B + are more sensitive to PI3K-inhibition, suggesting these tumors are more dependent + on Pi3K activation to thrive. Although tumors show partial response early + on, they inevitably relapsed, begging for an understanding of innate and selected + drug-resistant mechanisms. To this end, we have completed large-scale RNAseq + and whole exome sequencing (WES), and have performed in-depth analyses on + the mouse genomics data to identify genetic alternations including chromosomal + number variations (CNVs), mutations and gene fusions. Focusing on gene-fusions, + we found that by targeting these fusions, we can achieve better treatment + outcomes and in some cases, even complete tumor remission. Significantly TCGA + data analyses revealed the presence of similar fusions in human TNBC patients + and we are in the process of investigating whether human cells carrying these + fusions respond equally well compared to their mouse counterparts. Our approach + of precision-medicine guided treatment optimization has lead to substantially + improved treatment outcomes. Citation Format: Hui Liu, Charles Murphy, Florian + Karreth, Kangkang Yang, Gerburg Wulf, Lewis C. Cantley. Feasibility and efficacy + of a precision treatment approach for triple-negative breast cancer in mouse + models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American + Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia + (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3858.", "venue": "", + "year": 2016, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2016-07-15", "journal": {"volume": "76", "pages": "3858-3858", "name": "Cancer + Research"}, "authors": [{"authorId": "2146671919", "name": "Hui Liu"}, {"authorId": + "47107919", "name": "Charles J Murphy"}, {"authorId": "3566950", "name": "F. + Karreth"}, {"authorId": "2374780", "name": "Kangkang Yang"}, {"authorId": + "31554501", "name": "G. Wulf"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "657d88ef0ce8d9dd63f346ce70b958d84ca2c5cb", "externalIds": {"MAG": + "2333628861", "PubMedCentral": "4972100", "DOI": "10.1080/23723556.2016.1164280", + "CorpusId": 15560079, "PubMed": "27652319"}, "corpusId": 15560079, "publicationVenue": + {"id": "6150a680-d5fa-46f4-bfc0-c598ebcad821", "name": "Molecular & Cellular + Oncology", "type": "journal", "alternate_names": ["Mol Cell Oncol", "Molecular + and Cellular Oncology", "Mol Cell Oncol"], "issn": "2372-3556", "url": "http://www.tandfonline.com/loi/kmco20", + "alternate_urls": ["https://www.tandfonline.com/toc/kmco20/current"]}, "url": + "https://www.semanticscholar.org/paper/657d88ef0ce8d9dd63f346ce70b958d84ca2c5cb", + "title": "A novel small-molecule inhibitor of 3-phosphoglycerate dehydrogenase", + "abstract": "ABSTRACT Serine metabolism is likely to play a critical role + in cancer cell growth. A recent study reports the identification of a novel + small-molecule inhibitor of serine synthesis that targets 3-phosphoglycerate + dehydrogenase (PHGDH), the first enzyme of the serine synthesis pathway, and + selectively abrogates the proliferation of PHGDH overexpressing breast cancer + cells.", "venue": "Molecular & Cellular Oncology", "year": 2016, "referenceCount": + 11, "citationCount": 21, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.tandfonline.com/doi/pdf/10.1080/23723556.2016.1164280?needAccess=true", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2016-03-30", "journal": {"volume": "3", "name": "Molecular + & Cellular Oncology"}, "authors": [{"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "6627833", "name": "L. Lairson"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4901222", "name": "C. Lyssiotis"}]}, + {"paperId": "6ed33b6c25c025e1722a8a0a60aa31ed92fa9311", "externalIds": {"MAG": + "2516006356", "DOI": "10.1038/nature19084", "CorpusId": 4460906, "PubMed": + "27509858"}, "corpusId": 4460906, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/6ed33b6c25c025e1722a8a0a60aa31ed92fa9311", + "title": "Pancreatic stellate cells support tumour metabolism through autophagic + alanine secretion", "abstract": null, "venue": "Nature", "year": 2016, "referenceCount": + 28, "citationCount": 706, "influentialCitationCount": 26, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc5228623?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2016-08-25", "journal": {"volume": + "536", "pages": "479-483", "name": "Nature"}, "authors": [{"authorId": "48247953", + "name": "C. Sousa"}, {"authorId": "4430860", "name": "Douglas E Biancur"}, + {"authorId": "48631933", "name": "Xiaoxu Wang"}, {"authorId": "7745600", "name": + "C. Halbrook"}, {"authorId": "5238907", "name": "M. Sherman"}, {"authorId": + "2152827103", "name": "Li Zhang"}, {"authorId": "40237579", "name": "D. Kremer"}, + {"authorId": "4159648", "name": "R. Hwang"}, {"authorId": "4862030", "name": + "Agnes K. Witkiewicz"}, {"authorId": "33312849", "name": "H. Ying"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "2115604337", "name": "Ronald + M. Evans"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "4668673", "name": "A. Kimmelman"}]}, + {"paperId": "7a29bb5a459e594b29b5cd4f41a4feff54620a7a", "externalIds": {"DOI": + "10.1073/pnas.1607478113", "CorpusId": 205280513, "PubMed": "27330087"}, "corpusId": + 205280513, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7a29bb5a459e594b29b5cd4f41a4feff54620a7a", + "title": "Correction for Taniguchi et al., Phosphoinositide 3-kinase regulatory + subunit p85\u03b1 suppresses insulin action via positive regulation of PTEN", + "abstract": "MEDICAL SCIENCES Correction for \u201cPhosphoinositide 3-kinase + regulatory subunit p85\u03b1 suppresses insulin action via positive regulation + of PTEN,\u201d by Cullen M. Taniguchi, Thien T. Tran, Tatsuya Kondo, Ji Luo, + Kohjiro Ueki, Lewis C. Cantley, and C. Ronald Kahn, which appeared in issue + 32, August 8, 2006, of Proc Natl Acad Sci USA (103:12093\u201312097; first + published July 31, 2006; 10.1073/pnas.0604628103). The authors wish to note + the following: \u201cDue to an error during preparation of the manuscript, + the original Fig. 4A in this manuscript showing examples of PIP3 staining + contained two panels (the lox/lox sample at 0 min and the KO at 15 min) from + animals that were not a part of this study. A corrected version of Fig. 4A + is now shown below containing the correct representative examples of the staining + in each genotype at each time point. We have also repeated the quantitative + analysis of the staining intensity, derived from the recovered images, and + include a new version of Fig. 4B as well. This is not significantly different + from the original Fig. 4B and supports the original conclusion that p85 is + involved in the regulation of PTEN and PIP3 turnover. We apologize for any + confusion that this mistake may have caused.\u201d The corrected Fig. 4 and + its legend appear below.", "venue": "Proceedings of the National Academy of + Sciences", "year": 2016, "referenceCount": 0, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/113/25/E3588.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2016-06-02", "journal": + {"volume": "113", "pages": "E3588 - E3588", "name": "Proceedings of the National + Academy of Sciences"}, "authors": [{"authorId": "48311527", "name": "C. Taniguchi"}, + {"authorId": "3500862", "name": "T. Tran"}, {"authorId": "5177377", "name": + "K. Ueki"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144391716", + "name": "C. Kahn"}]}, {"paperId": "7b6fabe7f724e42a9460e5aadea8024161cb9858", + "externalIds": {"MAG": "2565103342", "DOI": "10.1158/1538-7445.PANCA16-B04", + "CorpusId": 56670047}, "corpusId": 56670047, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/7b6fabe7f724e42a9460e5aadea8024161cb9858", + "title": "Abstract B04: NRF2 regulates serine biosynthesis in pancreatic ductal + adenocarcinoma", "abstract": "Tumors have high energetic and anabolic needs + for rapid growth and proliferation, and the serine biosynthetic pathway has + recently been identified as an important source of metabolic intermediates + for these processes. We recently demonstrated that a substantial fraction + of NSCLC cell lines displayed significant serine/glycine biosynthetic activity + due to KEAP1 and NRF2 mutations (DeNicola et al. Nature Genetics 2015). We + demonstrated that NRF2 regulates glucose flux to serine by controlling transcription + of serine biosynthetic genes through the transcription factor ATF4. Importantly, + elevated expression of these genes conferred poor prognosis in human NSCLC. + Thus, a substantial fraction of human NSCLC activates an NRF2-dependent transcriptional + network that regulates serine and glycine metabolism and is linked to clinical + aggressiveness. Pancreatic ductal adenocarcinoma (PDAC) also demonstrates + high NRF2 activity due to mutations in KRAS and high MAPK signaling (DeNicola + et al. Nature 2011). We demonstrate that serine biosynthesis enzyme expression + is elevated in a mouse model of PDAC and that NRF2 regulates PHGDH expression + in human PDAC cell lines. Furthermore, PDAC cell lines are resistant to serine + starvation. PHGDH knockdown impairs the growth of tumor organoid orthotopic + transplants, and the role of PHGDH in tumor maintenance is currently being + investigated. These results suggest that the serine biosynthesis pathway is + regulated by NRF2 in multiple cancers and may be an important therapeutic + target. Citation Format: Gina M. DeNicola, Pei-Hsuan Chen, Edouard Mullarky, + Christine Chio, John M. Asara, John D. Minna, David A. Tuveson, Ralph J. DeBerardinis, + Lewis C. Cantley.{Authors}. NRF2 regulates serine biosynthesis in pancreatic + ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference + on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; + Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract + nr B04.", "venue": "", "year": 2016, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-12-15", "journal": {"volume": + "76", "name": "Cancer Research"}, "authors": [{"authorId": "4772111", "name": + "G. DeNicola"}, {"authorId": "4047142", "name": "Pei-Hsuan Chen"}, {"authorId": + "6424987", "name": "Edouard Mullarky"}, {"authorId": "39609817", "name": "C. + Chio"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "2996220", + "name": "J. Minna"}, {"authorId": "4530161", "name": "D. Tuveson"}, {"authorId": + "5834413", "name": "R. Deberardinis"}, {"authorId": "1723755", "name": "L. + Cantley"}]}, {"paperId": "7be9cb2a8d17c8ce037d95fca0be7c3f08ff0e6e", "externalIds": + {"MAG": "2343358448", "DOI": "10.1158/1078-0432.CCR-16-0134", "CorpusId": + 21431138, "PubMed": "27126994"}, "corpusId": 21431138, "publicationVenue": + {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", "name": "Clinical Cancer Research", + "type": "journal", "alternate_names": ["Clin Cancer Res"], "issn": "1078-0432", + "url": "https://clincancerres.aacrjournals.org/", "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/7be9cb2a8d17c8ce037d95fca0be7c3f08ff0e6e", + "title": "A Phase Ib Study of Alpelisib (BYL719), a PI3K\u03b1-Specific Inhibitor, + with Letrozole in ER+/HER2\u2212 Metastatic Breast Cancer", "abstract": "Purpose: + Alpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit + p110\u03b1, has shown synergistic antitumor activity with endocrine therapy + against ER+/PIK3CA-mutated breast cancer cells. This phase Ib study evaluated + alpelisib plus letrozole''s safety, tolerability, and preliminary activity + in patients with metastatic ER+ breast cancer refractory to endocrine therapy. + Experimental Design: Twenty-six patients received letrozole and alpelisib + daily. Outcomes were assessed by standard solid-tumor phase I methods. Tumor + blocks were collected for DNA extraction and next-generation sequencing. Results: + Alpelisib''s maximum-tolerated dose (MTD) in combination with letrozole was + 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, + fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d + of alpelisib. The clinical benefit rate (lack of progression \u22656 months) + was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; + 95% CI, 17%\u201356%), including five objective responses. Of eight patients + remaining on treatment \u226512 months, six had tumors with a PIK3CA mutation. + Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 + mutations did not derive clinical benefit. Overexpression of FGFR1 in ER+/PIK3CA + mutant breast cancer cells attenuated the response to alpelisib in vitro. + Conclusions: The combination of letrozole and alpelisib was safe, with reversible + toxicities. Clinical activity was observed independently of PIK3CA mutation + status, although clinical benefit was seen in a higher proportion of patients + with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine + therapy in patients with ER+ breast cancer are ongoing. Clin Cancer Res; 23(1); + 26\u201334. \u00a92016 AACR.", "venue": "Clinical Cancer Research", "year": + 2016, "referenceCount": 38, "citationCount": 215, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc5085926?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Study", + "JournalArticle", "ClinicalTrial"], "publicationDate": "2016-04-28", "journal": + {"volume": "23", "pages": "26 - 34", "name": "Clinical Cancer Research"}, + "authors": [{"authorId": "2346140", "name": "I. Mayer"}, {"authorId": "2186029", + "name": "V. Abramson"}, {"authorId": "40940752", "name": "L. Formisano"}, + {"authorId": "66935619", "name": "J. Balko"}, {"authorId": "144820856", "name": + "M. V. Estrada"}, {"authorId": "46945931", "name": "M. Sanders"}, {"authorId": + "3342243", "name": "D. Juric"}, {"authorId": "2344124", "name": "D. Solit"}, + {"authorId": "33727638", "name": "M. Berger"}, {"authorId": "3738649", "name": + "H. Won"}, {"authorId": "2111151410", "name": "Yisheng Li"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2369378", "name": "E. Winer"}, + {"authorId": "2057460", "name": "C. Arteaga"}]}, {"paperId": "838ca9a063f858f482d3edd34ea7dcb800137f71", + "externalIds": {"MAG": "2507391242", "CorpusId": 100002922}, "corpusId": 100002922, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/838ca9a063f858f482d3edd34ea7dcb800137f71", + "title": "(acidification of coated vesicles/endocytosis/receptors)", "abstract": + "Clathrin-coated vesicles isolated from calf brain contain an ATP-dependent + proton pump. Proton movement was monitored by measuring (''4C)methylamine + distribution. Addition of Mg2+ and ATP to coated vesicles equilibrated with + (''4C)methyl- amine resulted in the generation of a 4- to 5-fold concentration + gra- dient, corresponding to a ApH of 0.6-0.7 units between the medi- um and + the acidic inside of the coated vesicles. ATP-dependent (''4C)methylamine + uptake was abolished by the proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone + (FCCP) and partially inhibited by the carboxyl reagent N,N''-dicyclohex- ylcarbodiimide + but was unaffected by the Na+,K+-ATPase inhib- itors strophanthidin (100 /M) + and vanadate (10 j/M) and the mi- tochondrial ATPase inhibitors oligomycin + (10 j/g/ml) and aurovertin (1 /g/ml). GTP, but not the nonhydrolyzable analog + 5''-adenylyl imidodiphosphate, could support (''4C)methylamine uptake. Dis- + sipation of the membrane potential with K+ and valinomycin re- sulted in stimulation + of (14C)methylamine uptake, whereas both FCCP and valinomycin stimulated the + strophanthidin-resistant ATPase activity. These results are consistent with + the existence of an electrogenic, ATP-dependent proton pump in clathrin-coated + vesicles. This proton pump may play a role in the acidification events that + are essential in receptor-mediated endocytosis.", "venue": "", "year": 2016, + "referenceCount": 1, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "name": ""}, "authors": [{"authorId": "145289081", "name": "M. Forgac"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "93116398", "name": "Bertram + Wiede"}, {"authorId": "94066139", "name": "Daniel BRANTONt"}]}, {"paperId": + "8a56b6744f943c407c2a6fce4d2324c13cf14651", "externalIds": {"MAG": "2611308394", + "DOI": "10.1182/BLOOD.V128.22.610.610", "CorpusId": 56688751}, "corpusId": + 56688751, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/8a56b6744f943c407c2a6fce4d2324c13cf14651", + "title": "PIK3IP1 Inhibition of PI3K in G1 Arrest Induced By CDK4 Inhibition + Reprograms MCL for Ibrutinib Therapy", "abstract": "Inhibition of CDK4/6 has + emerged as a promising therapy for diverse human cancers. Mantle cell lymphoma + (MCL), in which aberrant cyclin D1 expression and CDK4 activity underlie unrestrained + proliferation of tumor cells, remains incurable. Targeting Bruton tyrosine + kinase (BTK) with ibrutinibin recurrent MCLhas unprecedented single agent + activity, with a completion remission (CR) rate of 21%. However, progression + on ibrutinib is virtually universal in MCL and is associated with aggressive + proliferation of tumor cells and a dismal clinical outcome. By longitudinal + integrated RNA- and exome-seq analysis, we previously discovered a mutation + in the ibrutinib binding site (BTKC481S) in MCL that was specific to relapse + from a durable response, but absent in both primary resistance and resistance + following a transient response. Irrespective of mechanism, ibrutinib resistance + was associated with enhanced PI3K activation as determined by Western blotting + of MCL cells isolated from serial biopsies. Induction of prolonged early G1 + arrest (pG1) by selective inhibition of CDK4 with palbociclib sensitized to + PI3K inhibition independent of this BTK mutation and to ibrutinib when the + wild type BTK was retained. In both cases, synergistic killing appears to + occur via cooperative inactivation of PI3K. Collectively, our data suggest + that dual inhibition of CDK4 and BTK or PI3K restrain the expansion of resistant + clones or even eliminate them to deepen or prolong the clinical response to + targeting BTK. To test this hypothesis, we initiated a phase I clinical trial + of palbociclib plus ibrutinib in recurrent MCL patients in August of 2014. + All 5 dose levels included ibrutinib daily and palbociclib administered on + days 1-21 of each 28-day cycle (Figure 1). Based on an intent-to-treat analysis + of 18 patients, 12 (67%) patients have responded to treatment including 8 + (44%) complete responses (CR). The median time to CR was 3 cycles and no responding + patients have progressed on study. The therapy was well tolerated (see ASH + abstract by Martin et al for clinical information). RNA- and exome-seq were + performed to assess the genomic alternations and gene expression on purified + MCL cells from samples before therapy, on progression and on treatment from + PR patients. Initial analysis did not detect non-synonymous mutation in CDK4, + CCND1, or genes in the BCR or PI3K signaling pathway. Hemizygous deletion + of Rb, p53, ATM and the INK4A/B locus and amplification of PIK3CA and PIK3CB + occurred in 30-50 % of patients before therapy. These copy number variations + were predominantly associated with primary resistance (4 subjects) but did + not preclude CR or PR. By contrast, expression of PIK3IP1, a putative PI3K + inhibitor, was markedly reduced on progression in all primary resistant patients, + but not in the PR patient. Function studies demonstrated that PIK3IP1 was + required for pG1 sensitization to BTK and PI3K inhibition in MCL cells in + vitro. Moreover, PIK3IP1 was induced in pG1 together PI3K inhibition in MCL + cells in patients responding to palbociclib alone in a separate clinical trial + (Martin, DiLiberto et al, unpublished), suggesting that PIK3IP1 mediates pG1 + reprogramming. In summary, the high CR rate and durability support our hypothesis + that induction of prolonged early G1 arrest by CDK4 inhibition reprograms + MCL cells for deepened and durable targeting of BTK in MCL. Our data further + suggest inhibition of PI3K by PIK3IP1 as a potential mechanism to overcome + ibrutinib resistance. A phase II multi-center clinical trial is planned to + further elucidate the genes and mechanisms that discriminate sensitivity from + resistance to dual targeting of CDK4 and BTK. Disclosures Blum:Pharmacyclics: + Research Funding. Ruan:Pharmacyclics: Research Funding, Speakers Bureau. Martin:Janssen: + Consultancy, Honoraria, Other: travel, accommodations, expenses; Celgene: + Consultancy, Honoraria; Gilead: Consultancy, Other: travel, accommodations, + expenses; Novartis: Consultancy; Acerta: Consultancy; Teva: Research Funding.", + "venue": "", "year": 2016, "referenceCount": 0, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-12-02", "journal": {"volume": + "128", "pages": "610-610", "name": "Blood"}, "authors": [{"authorId": "52430482", + "name": "M. Liberto"}, {"authorId": "22172195", "name": "Xiangao Huang"}, + {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": "30850515", + "name": "K. Eng"}, {"authorId": "5026467", "name": "K. Blum"}, {"authorId": + "3111840", "name": "N. Bartlett"}, {"authorId": "2115196348", "name": "Steven + I. Park"}, {"authorId": "2588907", "name": "J. Ruan"}, {"authorId": "3536873", + "name": "K. Maddocks"}, {"authorId": "2536360", "name": "G. Inghirami"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144240302", "name": "J. Leonard"}, + {"authorId": "144085617", "name": "P. Martin"}, {"authorId": "1398158850", + "name": "S. Chen\u2010Kiang"}]}, {"paperId": "97af5ddd9f193e5472d9c9278e2b8fca04e056d9", + "externalIds": {"MAG": "2342741787", "PubMedCentral": "4738311", "DOI": "10.1038/srep20471", + "CorpusId": 17554242, "PubMed": "26839216"}, "corpusId": 17554242, "publicationVenue": + {"id": "f99f77b7-b1b6-44d3-984a-f288e9884b9b", "name": "Scientific Reports", + "type": "journal", "alternate_names": ["Sci Rep"], "issn": "2045-2322", "url": + "http://www.nature.com/srep/", "alternate_urls": ["http://www.nature.com/srep/index.html"]}, + "url": "https://www.semanticscholar.org/paper/97af5ddd9f193e5472d9c9278e2b8fca04e056d9", + "title": "A Cross-Species Study of PI3K Protein-Protein Interactions Reveals + the Direct Interaction of P85 and SHP2", "abstract": null, "venue": "Scientific + Reports", "year": 2016, "referenceCount": 66, "citationCount": 35, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/srep20471.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2016-02-03", "journal": {"volume": + "6", "name": "Scientific Reports"}, "authors": [{"authorId": "3739417", "name": + "S. Breitkopf"}, {"authorId": "48520140", "name": "Xuemei Yang"}, {"authorId": + "69874482", "name": "M. Begley"}, {"authorId": "33373476", "name": "Meghana + Kulkarni"}, {"authorId": "47591147", "name": "Y. Chiu"}, {"authorId": "4039016", + "name": "Alexa B. Turke"}, {"authorId": "4978543", "name": "Jessica Lauriol"}, + {"authorId": "49059923", "name": "M. Yuan"}, {"authorId": "46315599", "name": + "J. Qi"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "145595134", + "name": "Pengyu Hong"}, {"authorId": "5806645", "name": "M. Kontaridis"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2001255", "name": + "N. Perrimon"}, {"authorId": "3028470", "name": "J. Asara"}]}, {"paperId": + "9829e1fd2a50eeb9a2f15370acc12317449759e8", "externalIds": {"MAG": "2588573341", + "DOI": "10.1016/J.CMET.2016.01.016", "CorpusId": 90115792}, "corpusId": 90115792, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9829e1fd2a50eeb9a2f15370acc12317449759e8", + "title": "Erratum: Divergent regulation of hepatic glucose and lipid metabolism + by phosphoinositide 3-kinase via Akt and PKC\u03bb/\u03b6 (Cell Metabolism + (2006) 3 (343-353))", "abstract": null, "venue": "", "year": 2016, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1550413116300092/pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-02-09", "journal": {"volume": + "23", "name": "Cell Metabolism"}, "authors": [{"authorId": "48311527", "name": + "C. Taniguchi"}, {"authorId": "16114256", "name": "Tatsuya Kondo"}, {"authorId": + "3511388", "name": "M. Sajan"}, {"authorId": "145954100", "name": "Ji Luo"}, + {"authorId": "40803408", "name": "R. Bronson"}, {"authorId": "1928077", "name": + "T. Asano"}, {"authorId": "5937884", "name": "Robert V Farese"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": "C. Kahn"}]}, + {"paperId": "9a376d60eea4b39dae4c68e5997adb4a9158dc76", "externalIds": {"MAG": + "2915338336", "DOI": "10.1158/1538-7445.AM2016-4165", "CorpusId": 86701488}, + "corpusId": 86701488, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9a376d60eea4b39dae4c68e5997adb4a9158dc76", + "title": "Abstract 4165: Myc vs. Akt therapy in RapidCap, a GEM model for + metastatic prostate cancer", "abstract": "We describe our efforts to determine + the effect of MYC and PI3K inhibition in a genetically engineered mouse model + of naive and castration-resistant metastatic prostate cancer. Metastasis is + a major driver of mortality and morbidity in prostate cancer, the most common + cancer type in men and the second leading cause of cancer-related deaths in + the western world. To recapitulate the metastatic process in genetically engineered + mice, we have developed the RapidCaP system, which uses prostate-directed + viral infection to trigger focal loss of Pten and Trp53. Using luminescence + and fluorescence, the RapidCaP system allows us to track disease progression + in real-time and isolate metastases in distant tissues. This system provides + a powerful platform for the identification and validation of candidate driver + genes and for the efficient testing of novel therapeutics. Using this system, + we have recently identified Myc as a critical, spontaneously activated driver + in Pten-negative metastatic prostate cancer. Preliminary trials indicate that + the Myc-suppressing Brd4 inhibitor JQ1 is ineffective towards primary disease, + but induces metastatic regression. This specificity correlates with a switch + from AKT-driven primary disease to MYC-driven metastatic disease. Our current + efforts seek to determine how, when and why targeting of Myc using JQ1 and + the PI 3-Kinase pathway using NVP-BKM120 can be best used to treat naive and + castration-resistant metastatic prostate cancer. In addition, we are examining + changes to the transcriptome and epigenetic alterations that characterize + Pten-negative metastatic prostate cancer, with the goal of understanding the + mechanisms of progression toward a metastatic state and establishing new therapeutic + targets. Citation Format: Carlos E. Stahlhut, Alexandra J. Ambrico, Kaitlin + E. Watrud, Hyejin Cho, Lily Wang, Jun Qi, Lewis C. Cantley, James Bradner, + Lloyd Trotman. Myc vs. Akt therapy in RapidCap, a GEM model for metastatic + prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of + the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, + LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4165.", + "venue": "", "year": 2016, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2016-07-15", "journal": {"volume": "76", "pages": "4165-4165", "name": "Cancer + Research"}, "authors": [{"authorId": "47270173", "name": "C. Stahlhut"}, {"authorId": + "15976560", "name": "A. Ambrico"}, {"authorId": "10426666", "name": "Kaitlin + Watrud"}, {"authorId": "4485082", "name": "Hyejin Cho"}, {"authorId": "2117931332", + "name": "Lily C. Wang"}, {"authorId": "145752082", "name": "J. Qi"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3685746", "name": "J. Bradner"}, + {"authorId": "4603490", "name": "L. Trotman"}]}, {"paperId": "9be2e2f64408fd8d4c823d3bb145309598b43d16", + "externalIds": {"CorpusId": 163162060}, "corpusId": 163162060, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/9be2e2f64408fd8d4c823d3bb145309598b43d16", + "title": "The primary pathway from PI 3 K to mTORC 1 : switching on Rheb", + "abstract": "The class I phosphoinositide 3-kinase (PI3K) mechanistic target + of rapamycin complex 1 (mTORC1) signaling network directs cellular metabolism + and growth. Activation of mTORC1, which is composed of mTOR, Raptor, mLST8, + PRAS40, and DEPTOR, depends on the Rag and Rheb GTPases, and requires signals + from amino acids, glucose, oxygen, energy (ATP), and growth factors (including + cytokines and hormones such as insulin). Here we discuss the signal transduction + mechanisms through which growth factor-responsive PI3K signaling activates + mTORC1. We focus on how PI3K-dependent activation of Akt and spatial regulation + of the TSC complex (composed of TSC1, TSC2, and TBC1D7) switches on Rheb at + the lysosome, where mTORC1 is activated. Integration of PI3Kand amino acid-dependent + signals upstream of mTORC1 at the lysosome is detailed in a working model. + A coherent understanding of the PI3KmTORC1 network is imperative as its dysregulation + has been implicated in diverse pathologies including cancer, diabetes, autism, + and aging.", "venue": "", "year": 2016, "referenceCount": 154, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + null, "authors": [{"authorId": "7449887", "name": "Christian C. Dibble"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "a4a62f41776983c72d52b9f028c833e040cffed9", + "externalIds": {"MAG": "2497980300", "DOI": "10.1007/978-3-319-34211-5_1", + "CorpusId": 89590127}, "corpusId": 89590127, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/a4a62f41776983c72d52b9f028c833e040cffed9", + "title": "PI3K-Akt-mTOR Signaling in Cancer and Cancer Therapeutics", "abstract": + null, "venue": "", "year": 2016, "referenceCount": 124, "citationCount": 1, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": {"volume": "", "pages": "1-25", "name": + ""}, "authors": [{"authorId": "49926666", "name": "S. Chopra"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "a6e601eee09639ec90db79cceaf5922f7dc45f5f", + "externalIds": {"MAG": "2486295304", "DOI": "10.1158/1538-7445.AM2016-4979", + "CorpusId": 78956513}, "corpusId": 78956513, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/a6e601eee09639ec90db79cceaf5922f7dc45f5f", + "title": "Abstract 4979: Cabozantinib eradicates advanced murine prostate + cancer by activating neutrophil-mediated anti-tumor innate immunity", "abstract": + "Several kinase inhibitors targeting aberrant signaling pathways in tumor + cells have been deployed in cancer therapy. However, their impact on the tumor + immune microenvironment remains poorly understood. The tyrosine kinase inhibitor + cabozantinib showed striking responses in cancer clinical trial patients across + several malignancies. Here we show that cabozantinib rapidly eradicates invasive, + poorly-differentiated PTEN/p53 deficient murine prostate cancer. This was + associated with enhanced release of neutrophil chemotactic factors from tumor + cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils + into the tumor. Critically, cabozantinib-induced tumor clearance in mice was + abolished by antibody-mediated granulocyte depletion or HMGB1 neutralization + or blockade of neutrophil chemotaxis with the CXCR4 inhibitor, plerixafor. + Collectively, these data demonstrate that cabozantinib triggers a neutrophil-mediated + anti-tumor innate immune response, resulting in rapid tumor clearance. Citation + Format: Akash Patnaik, Kenneth D. Swanson, Eva Csizmadia, Marina P. Gehring, + Katja Helenius, Athalia R. Pyzer, Lily C. Wang, Jesse Novak, Olivier Elemento, + Thomas B. Thornley, John M. Asara, John G. Clohessy, Kathy Kelly, Pier Paolo + Pandolfi, Jacalyn M. Rosenblatt, David E. Avigan, Huihui Ye, Sabina Signoretti, + Steven P. Balk, Lewis C. Cantley. Cabozantinib eradicates advanced murine + prostate cancer by activating neutrophil-mediated anti-tumor innate immunity. + [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association + for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; + Cancer Res 2016;76(14 Suppl):Abstract nr 4979.", "venue": "", "year": 2016, + "referenceCount": 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2016-07-15", + "journal": {"volume": "76", "pages": "4979-4979", "name": "Cancer Research"}, + "authors": [{"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": "6784962", + "name": "K. Swanson"}, {"authorId": "4793517", "name": "E. Csizmadia"}, {"authorId": + "33820964", "name": "M. Gehring"}, {"authorId": "49804844", "name": "Katja + Helenius"}, {"authorId": "15061933", "name": "A. Pyzer"}, {"authorId": "2117931332", + "name": "Lily C. Wang"}, {"authorId": "50577147", "name": "Jesse S. Novak"}, + {"authorId": "150097652", "name": "O. Elemento"}, {"authorId": "4374091", + "name": "T. Thornley"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "4102988", "name": "J. Clohessy"}, {"authorId": "145953924", "name": "K. Kelly"}, + {"authorId": "4499580", "name": "P. Pandolfi"}, {"authorId": "31499217", "name": + "J. Rosenblatt"}, {"authorId": "145881219", "name": "D. Avigan"}, {"authorId": + "3073381", "name": "Huihui Ye"}, {"authorId": "7505152", "name": "S. Signoretti"}, + {"authorId": "6189162", "name": "S. Balk"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "a9db948b3a66f190fd042cbe86a1c227b791aff2", "externalIds": + {"DOI": "10.1038/nature19851", "CorpusId": 4447244, "PubMed": "27706144"}, + "corpusId": 4447244, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/a9db948b3a66f190fd042cbe86a1c227b791aff2", + "title": "Erratum: Pancreatic stellate cells support tumour metabolism through + autophagic alanine secretion", "abstract": null, "venue": "Nature", "year": + 2016, "referenceCount": 0, "citationCount": 16, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/nature19851.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "540", "pages": "150-150", + "name": "Nature"}, "authors": [{"authorId": "48247953", "name": "C. Sousa"}, + {"authorId": "4430860", "name": "Douglas E Biancur"}, {"authorId": "48631933", + "name": "Xiaoxu Wang"}, {"authorId": "7745600", "name": "C. Halbrook"}, {"authorId": + "5238907", "name": "M. Sherman"}, {"authorId": "2152827103", "name": "Li Zhang"}, + {"authorId": "40237579", "name": "D. Kremer"}, {"authorId": "4159648", "name": + "R. Hwang"}, {"authorId": "4862030", "name": "Agnes K. Witkiewicz"}, {"authorId": + "33312849", "name": "H. Ying"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "2115604337", "name": "Ronald M. Evans"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "4668673", "name": "A. Kimmelman"}]}, {"paperId": "b0fccaf2d7aafafc516312a14ac1d6e64a3b04f1", + "externalIds": {"CorpusId": 189807495}, "corpusId": 189807495, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b0fccaf2d7aafafc516312a14ac1d6e64a3b04f1", + "title": "NRF 2 regulates serine biosynthesis in non-small cell lung cancer", + "abstract": null, "venue": "", "year": 2016, "referenceCount": 30, "citationCount": + 42, "influentialCitationCount": 2, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "4772111", "name": "G. DeNicola"}, + {"authorId": "4047142", "name": "Pei-Hsuan Chen"}, {"authorId": "6424987", + "name": "Edouard Mullarky"}, {"authorId": "5467431", "name": "J. Sudderth"}, + {"authorId": "2102981938", "name": "Zeping"}, {"authorId": "2054591351", "name": + "Hu"}, {"authorId": "144790190", "name": "David Wu"}, {"authorId": "2112388600", + "name": "Hao Tang"}, {"authorId": "145668114", "name": "Yang Xie"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "5305256", "name": "K. Huffman"}, + {"authorId": "145606732", "name": "I. Ignacio"}, {"authorId": "89777075", + "name": "Wistuba"}, {"authorId": "2996220", "name": "J. Minna"}, {"authorId": + "5834413", "name": "R. Deberardinis"}, {"authorId": "1723755", "name": "L. + Cantley"}]}, {"paperId": "b7984aa5258f2ae0b7f36f8afd6114f99a2516d6", "externalIds": + {"MAG": "2254906934", "DOI": "10.1016/j.cell.2015.12.042", "CorpusId": 1991479, + "PubMed": "26824656"}, "corpusId": 1991479, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/b7984aa5258f2ae0b7f36f8afd6114f99a2516d6", + "title": "Phosphoinositide 3-Kinase Regulates Glycolysis through Mobilization + of Aldolase from the Actin Cytoskeleton", "abstract": null, "venue": "Cell", + "year": 2016, "referenceCount": 40, "citationCount": 252, "influentialCitationCount": + 8, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867415017067/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2016-01-28", "journal": {"volume": "164", "pages": "433-446", + "name": "Cell"}, "authors": [{"authorId": "113164867", "name": "Hai Hu"}, + {"authorId": "49149990", "name": "Ashish Juvekar"}, {"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "4729701", "name": "Evan C. Lien"}, + {"authorId": "2791479", "name": "J. Albeck"}, {"authorId": "49643144", "name": + "D. Oh"}, {"authorId": "144092031", "name": "G. Varma"}, {"authorId": "33910582", + "name": "Y. Hung"}, {"authorId": "50136879", "name": "Soumya Ullas"}, {"authorId": + "6974291", "name": "J. Lauring"}, {"authorId": "143667851", "name": "P. Seth"}, + {"authorId": "49142390", "name": "Mark R. Lundquist"}, {"authorId": "6482179", + "name": "D. Tolan"}, {"authorId": "33624537", "name": "A. Grant"}, {"authorId": + "3757436", "name": "D. Needleman"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "31554501", "name": + "G. Wulf"}]}, {"paperId": "c5e715daaab960c84c9f4e7aa642ee35c424a167", "externalIds": + {"MAG": "2401609195", "DOI": "10.1158/1557-3265.OVCA15-IA08", "CorpusId": + 88527865}, "corpusId": 88527865, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/c5e715daaab960c84c9f4e7aa642ee35c424a167", + "title": "Abstract IA08: PI3K- and PARP-inhibitors for the treatment of women + cancers.", "abstract": "Amplification of PIK3CA is highly prevalent in ovarian + cancer and isoform-specific and pan-PI3K inhibitors have entered clinical + trials. However, identifying tumor subtypes and biological mechanisms that + predict for response to PI3K inhibitors as single agents or in combination + has been a challenge. We previously reported that combining a phophoinositide + 3-kinase (PI3K) inhibitor with a poly ADP ribose polymerase (PARP)-inhibitor + enhanced DNA damage and cell death in breast cancers that have genetic aberrations + in BRCA1 and TP53. We now show that the enhanced DNA damage induced by PI3K + inhibitors in this mutational background is a consequence of impaired production + of deoxynucleotides needed for DNA synthesis and DNA repair. Inhibition of + PI3K causes a reduction in all four deoxynucleotide triphosphates (dATP, dTTP, + dGTP and dCTP), while inhibition of AKT is less effective than inhibition + of PI3K in suppressing nucleotide synthesis and inducing DNA damage. Carbon + flux studies reveal that PI3K-inhibition disproportionately affects the non-oxidative + pentose phosphate pathway (non-ox PPP) that delivers ribose-5-posphate required + for base ribosylation. In vivo in a mouse model of BRCA1-linked triple-negative + breast cancer combined PI3K- and PARP-inhibition was superior to either agent + alone to induce durable remissions of established tumors. Our data indicate + that PI3K inhibitors induce DNA damage in tumors that have defects in DNA + damage repair pathways and that they do so by impairing the production of + Ribose-5-phosphate and amino acids needed for deoxynucleotide synthesis. An + ongoing phase I/II study (NCT01623349, PI: Matulonis) examines the safety + and toxicity of a PI3K/Parp-inhibitor combination in ovarian and breast cancer. + Citation Format: Gerburg M. Wulf, Ashish Juvekar, Lewis C. Cantley, Ursula + A. Matulonis. PI3K- and PARP-inhibitors for the treatment of women cancers. + [abstract]. In: Proceedings of the AACR Special Conference on Advances in + Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, + FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr + IA08.", "venue": "", "year": 2016, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-01-15", "journal": {"volume": + "22", "name": "Clinical Cancer Research"}, "authors": [{"authorId": "31554501", + "name": "G. Wulf"}, {"authorId": "49149990", "name": "Ashish Juvekar"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6927295", "name": "U. Matulonis"}]}, + {"paperId": "c7e48adeb3fc5c49fc8318d1fb6edcd9a23fda14", "externalIds": {"MAG": + "2511108195", "DOI": "10.1093/med/9780199934522.003.0075", "CorpusId": 88923713}, + "corpusId": 88923713, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/c7e48adeb3fc5c49fc8318d1fb6edcd9a23fda14", + "title": "The PI3K-LKB1 Pathway", "abstract": null, "venue": "", "year": 2016, + "referenceCount": 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}], "publicationTypes": null, + "publicationDate": "2016-06-01", "journal": {"volume": "", "pages": "572-576", + "name": ""}, "authors": [{"authorId": "4426388", "name": "R. Shaw"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "d50448be8fbbbcf197db0bf875e4ed2084293d85", + "externalIds": {"MAG": "2596021293", "DOI": "10.1073/PNAS.1602228113", "CorpusId": + 139097192}, "corpusId": 139097192, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d50448be8fbbbcf197db0bf875e4ed2084293d85", + "title": "Erratum: Identification of a small molecule inhibitor of 3-phosphoglycerate + dehydrogenase to target serine biosynthesis in cancers (Proceedings of the + National Academy of Sciences of the United States of America (2016) 113 (1778-1783) + DOI:10.1073/pnas.1521548113)", "abstract": null, "venue": "", "year": 2016, + "referenceCount": 0, "citationCount": 6, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/113/11/E1585.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-03-15", "journal": {"volume": + "113", "name": "Proceedings of the National Academy of Sciences of the United + States of America"}, "authors": [{"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "6490745", "name": "N. Lucki"}, {"authorId": "3992718", + "name": "R. Zavareh"}, {"authorId": "35906509", "name": "J. Anglin"}, {"authorId": + "2087116099", "name": "Ana P Gomes"}, {"authorId": "4374034", "name": "Brandon + Nicolay"}, {"authorId": "40497062", "name": "Jenny C. Y. Wong"}, {"authorId": + "32173727", "name": "S. Christen"}, {"authorId": "2115843581", "name": "Hidenori + Takahashi"}, {"authorId": "2109204398", "name": "P. Singh"}, {"authorId": + "4037343", "name": "J. Blenis"}, {"authorId": "32988325", "name": "J. Warren"}, + {"authorId": "46775302", "name": "S. Fendt"}, {"authorId": "3028470", "name": + "J. Asara"}, {"authorId": "4772111", "name": "G. DeNicola"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "6627833", "name": "L. Lairson"}, + {"authorId": "1723755", "name": "L. Cantley"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '282200' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:39 GMT + Via: + - 1.1 3ba93a6ef49a771baec432f3334c38ca.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - 5HVYCkOS1FFTJnhyTNIIqOO5gXnvf9U5x1S_dmCXLNYYNYBUcArvQw== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOZ7GPxPHcF98Q= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '282200' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:39 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - d4e39366-59ee-4669-b8cd-67f0aec9f590 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=200&limit=100 + response: + body: + string: '{"offset": 200, "next": 300, "data": [{"paperId": "dc2f356dffee630c6dbf07ac2f5affc5f985a9e2", + "externalIds": {"MAG": "2552631557", "DOI": "10.1200/JCO.2016.67.9712", "CorpusId": + 45723038, "PubMed": "27903152"}, "corpusId": 45723038, "publicationVenue": + {"id": "a5913268-3957-484f-b41f-347b0ba23338", "name": "Journal of Clinical + Oncology", "type": "journal", "alternate_names": ["J Clin Oncol"], "issn": + "0732-183X", "url": "https://ascopubs.org/loi/jco", "alternate_urls": ["http://www.jco.org/", + "http://jco.ascopubs.org/"]}, "url": "https://www.semanticscholar.org/paper/dc2f356dffee630c6dbf07ac2f5affc5f985a9e2", + "title": "Obesity and Cancer Mechanisms: Cancer Metabolism.", "abstract": + "Obesity is a risk factor for cancer development and is associated with poor + prognosis in multiple tumor types. The positive energy balance linked with + obesity induces a variety of systemic changes including altered levels of + insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, + and cytokines. Each of these factors alters the nutritional milieu and has + the potential to create an environment that favors tumor initiation and progression. + Although the complete ramifications of obesity as it relates to cancer are + still unclear, there is convincing evidence that reducing the magnitude of + the systemic hormonal and inflammatory changes has significant clinical benefits. + This review will examine the changes that occur in the obese state and review + the biologic mechanisms that connect these changes to increased cancer risk. + Understanding the metabolic changes that occur in obese individuals may also + help to elucidate more effective treatment options for these patients when + they develop cancer. Moving forward, targeted clinical trials examining the + effects of behavioral modifications such as reduced carbohydrate intake, caloric + restriction, structured exercise, and/or pharmacologic interventions such + as the use of metformin, in obese populations may help to reduce their cancer + risk.", "venue": "Journal of Clinical Oncology", "year": 2016, "referenceCount": + 132, "citationCount": 169, "influentialCitationCount": 4, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc5562429?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2016-11-07", "journal": {"volume": + "34 35", "pages": "\n 4277-4283\n ", "name": "Journal of clinical + oncology : official journal of the American Society of Clinical Oncology"}, + "authors": [{"authorId": "48821307", "name": "B. Hopkins"}, {"authorId": "145524334", + "name": "M. Goncalves"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "e5066c55949b636d20c4f4abbb898d493f716d19", "externalIds": {"MAG": + "2479261316", "DOI": "10.1158/1538-7445.AM2016-159", "CorpusId": 78317911}, + "corpusId": 78317911, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e5066c55949b636d20c4f4abbb898d493f716d19", + "title": "Abstract 159: Analysis of resistance to the combination of a PI3K- + and Parp-inhibitor using a genomic sequencing approach", "abstract": "The + objective of this study is to investigate the genomic and transcriptonal changes + that are associated with resistance to treatment with the combination of a + PI3K-inhibitor (NVP-BKM120) and a PARP-inhibitor (Olaparib). Previous studies + have shown that the combination of a PI3K-inhibitor and a PARP-inhibitor synergistically + reduced the growth of BRCA-related xenograft tumors derived from patients + with TNBC. However, in clinical practice, primary and secondary resistance + to this combination is observed. We hypothesize that acquired resistance is + the result of a genomic evolution resulting from the selection pressure exerted + by the drug treatment. We used a genetically engineered mouse model, K14-Cre + BRCA1f/fp53f/f, where primary tumors had been propagated in Cre-negative littermates + and treated to point of resistance with NVP-BKM120 or NVP-BKM120 plus Olaparib. + For each of the three tumors, we analyzed exome sequencing and RNA-seq using + Illumina technology at the stage of sensitivity (C), resistance to PI3K-inhibition + (B) and resistance to the combination (BO); i.e. for each individual tumor + a parental clone and its drug-resistant subclones, obtained in vivo, were + analyzed. We used the Mutect software tool to call somatic mutations, VarScan2 + to call somatic copy number variations, Cuffdiff for differential expression + analysis, and TophatFusion. Data were integrated to identify genes for functional + analyses using MetaCore and MSigDB software tools. We found that tumors resistant + to the combination drug treatment in general had fewer gross genomic alterations + (CNVs) than parental tumors, indicative of evolution of a less variable subclone. + However, these tumors also displayed a higher number of non-synonymous mutations + than their parental clone. Pathway analysis showed that somatically mutated + genes in PI3K-inhibitor resistant tumors were highly enriched for antigen + processing and presentation, while those of tumors resistant to the combination + treatment were enriched for histone modification pathways. Notably, the tumors + resistant to PI3K-inhibitor alone were enriched for Insulin-processing pathways. + Genomic losses in PI3K-inhibitor treated tumors enriched for the estrogen + receptor pathway (ESR) in breast cancer and DNA damage pathways. In conclusion, + our experimental design of analyzing isogenic tumors resistant to PI3K- or + combined PI3K- and Parp-inhibitors enabled us to identify genomic alterations + and pathways that explain the evolution to drug resistance. Citation Format: + Sheida Nabavi, Ashish Juvekar, Nicholas Wang, Lewis C. Cantley, Gerburg M. + Wulf. Analysis of resistance to the combination of a PI3K- and Parp-inhibitor + using a genomic sequencing approach. [abstract]. In: Proceedings of the 107th + Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; + New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract + nr 159.", "venue": "", "year": 2016, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-07-15", "journal": {"volume": + "76", "pages": "159-159", "name": "Cancer Research"}, "authors": [{"authorId": + "145834073", "name": "S. Nabavi"}, {"authorId": "49149990", "name": "Ashish + Juvekar"}, {"authorId": "1722194", "name": "Nicholas J. Wang"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "31554501", "name": "G. Wulf"}]}, + {"paperId": "e8882437b636bac43abf4a413d3e46053351e732", "externalIds": {"MAG": + "2555512044", "DOI": "10.1158/1557-3125.CELLCYCLE16-IA08", "CorpusId": 88842212}, + "corpusId": 88842212, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e8882437b636bac43abf4a413d3e46053351e732", + "title": "Abstract IA08: Reprogramming human cancer cells in CDK4/6 inhibitor + therapy", "abstract": "CDK4 and CDK6 drive cell cycle progression through + early G1 and are frequently deregulated in human cancer. Selective inhibition + of CDK4/6 with palbociclib (PD 0332991) has demonstrated exciting clinical + efficacy in diverse human cancers. However, the mechanism that discriminates + sensitivity from resistance to targeting CDK4/6 remains obscure. Mantle cell + lymphoma (MCL) is an incurable non-Hodgkin9s lymphoma where deregulated CDK4 + activity and cyclin D1 expression underlies unrestrained proliferation and + disease progression. In a phase I clinical trial in recurrent MCL, we demonstrated + that palbociclib alone produced a durable clinical response with a favorable + toxicity profile. To investigate the mechanism for targeting CDK4/6, we have + now shown in primary cancer cells that 1) inhibition of CDK4/6 leads to early + G1 arrest that requires Rb, the CDK4/6 substrate; 2) prolonged early G1 arrest + (pG1) sensitizes Rb-proficient cancer cells to killing by diverse clinically-relevant + agents; and 3) pG1 sensitization stems from continuous expression of genes + scheduled for early G1 only. This leads to an imbalance in genes expression, + which is exacerbated in synchronous progression to S phase (pG1-S) after palbociclib + withdrawal, due to incomplete restoration of cell cycle-coupled gene expression. + In a hypothesis-driven phase Ib clinical trial, targeting CDK4 with palbociclib + in sequential combination with the proteasome inhibitor bortezoimb was well + tolerated (n=16). It exhibited a durable palbociclib dose-dependent clinical + activity, including one complete remission for over 3 years with only one + progression at the optimal dose combination (n=6). Longitudinal integrative + whole transcriptome and whole exome sequencing of tumor cells isolated from + serial lymph node biopsies demonstrated that palbociclib initially induced + pG1 in MCL cells of all patients, regardless of copy number variation or mutation + (ATM, p53). Cell cycle control by palbociclib is thus initially intact in + MCL, but is insufficient to predict the clinical response. As predicted, only + genes programmed for early G1 were expressed pG1, concurrent PI3K inactivation + in primary MCL cells. However, This study represents the first investigation + of genes that discriminate sensitivity from resistance in targeting CDK4/CDK6 + in human cancer, through integrative longitudinal analysis of whole exome + and whole transcriptome sequencing in concert with protein expression analysis + and functional studies. Selective inhibition of CDK4 induces pG1 in all MCL + patients, which apparently reprograms MCL for clinical response to bortezomib + through PI3K inactivation and suppression of genes for redox homeostasis. + Citation Format: Selina Chen-Kiang, Maurizio Di Liberto, Priyanka Vijay, David + Chiron, Xiangao Huang, Scott Ely, Olivier Elemento, Christopher Mason, Lewis + Cantley, John P. Leonard, Peter Martin. Reprogramming human cancer cells in + CDK4/6 inhibitor therapy. [abstract]. In: Proceedings of the AACR Precision + Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; + Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract + nr IA08.", "venue": "", "year": 2016, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-11-01", "journal": {"volume": + "14", "name": "Molecular Cancer Research"}, "authors": [{"authorId": "1398158850", + "name": "S. Chen\u2010Kiang"}, {"authorId": "52430482", "name": "M. Liberto"}, + {"authorId": "145792938", "name": "P. Vijay"}, {"authorId": "46863981", "name": + "D. Chiron"}, {"authorId": "22172195", "name": "Xiangao Huang"}, {"authorId": + "121580871", "name": "S. Ely"}, {"authorId": "150097652", "name": "O. Elemento"}, + {"authorId": "2959056", "name": "C. Mason"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "144240302", "name": "J. Leonard"}, {"authorId": + "144085617", "name": "P. Martin"}]}, {"paperId": "ece465807c23d42d275ffcce19ef06dd0b300f50", + "externalIds": {"MAG": "2395508446", "DOI": "10.1080/2162402X.2016.1145332", + "CorpusId": 34426042, "PubMed": "27471611"}, "corpusId": 34426042, "publicationVenue": + {"id": "1a084c30-2271-476c-b82a-439820433fe9", "name": "Oncoimmunology", "type": + "journal", "alternate_names": ["OncoImmunology"], "issn": "2162-4011", "url": + "http://www.landesbioscience.com/journals/oncoimmunology/", "alternate_urls": + ["https://www.tandfonline.com/KONI", "http://www.tandfonline.com/toc/koni20/current"]}, + "url": "https://www.semanticscholar.org/paper/ece465807c23d42d275ffcce19ef06dd0b300f50", + "title": "Prioritization schema for immunotherapy clinical trials in glioblastoma", + "abstract": "ABSTRACT Background: Emerging immunotherapeutic strategies for + the treatment of glioblastoma (GBM) such as dendritic cell (DC) vaccines, + heat shock proteins, peptide vaccines, and adoptive T-cell therapeutics, to + name a few, have transitioned from the bench to clinical trials. With upcoming + strategies and developing therapeutics, it is challenging to critically evaluate + the practical, clinical potential of individual approaches and to advise patients + on the most promising clinical trials. Methods: The authors propose a system + to prioritize such therapies in an organized and data-driven fashion. This + schema is based on four categories of factors: antigenic target robustness, + immune-activation and -effector responses, preclinical vetting, and early + evidence of clinical response. Each of these categories is subdivided to focus + on the most salient elements for developing a successful immunotherapeutic + approach for GBM, and a numerical score is generated. Results: The Score Card + reveals therapeutics that have the most robust data to support their use, + provides a reference prioritization score, and can be applied in a reiterative + fashion with emerging data. Conclusions: The authors hope that this schema + will give physicians an evidence-based and rational framework to make the + best referral decisions to better guide and serve this patient population.", + "venue": "Oncoimmunology", "year": 2016, "referenceCount": 231, "citationCount": + 30, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.tandfonline.com/doi/pdf/10.1080/2162402X.2016.1145332?needAccess=true", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "2016-02-18", + "journal": {"volume": "5", "name": "OncoImmunology"}, "authors": [{"authorId": + "6116001", "name": "T. Hodges"}, {"authorId": "5126443", "name": "S. Ferguson"}, + {"authorId": "7188898", "name": "H. Caruso"}, {"authorId": "4868530", "name": + "G. Kohanbash"}, {"authorId": "7523168", "name": "Shouhao Zhou"}, {"authorId": + "2718826", "name": "T. Cloughesy"}, {"authorId": "82318840", "name": "M. Berger"}, + {"authorId": "4715187", "name": "G. Poste"}, {"authorId": "113753345", "name": + "M. Khasraw"}, {"authorId": "36807854", "name": "Sujuan Ba"}, {"authorId": + "145909831", "name": "T. Jiang"}, {"authorId": "39284888", "name": "T. Mikkelson"}, + {"authorId": "143913370", "name": "W. Yung"}, {"authorId": "143802155", "name": + "J. D. de Groot"}, {"authorId": "3328992", "name": "H. Fine"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2569035", "name": "I. Mellinghoff"}, + {"authorId": "40173718", "name": "D. Mitchell"}, {"authorId": "2090005", "name": + "H. Okada"}, {"authorId": "6820582", "name": "A. Heimberger"}]}, {"paperId": + "ef05508cb2615e2807411ec18bb18fbcefda2455", "externalIds": {"MAG": "2478359261", + "DOI": "10.1158/1538-7445.AM2016-SY12-01", "CorpusId": 89071141}, "corpusId": + 89071141, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/ef05508cb2615e2807411ec18bb18fbcefda2455", + "title": "Abstract SY12-01: PI 3-kinase and cancer metabolism", "abstract": + "In general cancer cells produce higher levels of reactive oxygen species + (ROS) than normal cells due to increased rates of metabolism and defective + mitochondria. In order to survive under conditions of high ROS, cancer cells + typically turn on pathways for generating NADPH and glutathione to bring ROS + levels back to homeostasis. Activating mutations in PIK3CA or loss of PTEN + or activating mutations in KRAS can stimulate glucose uptake and metabolism + and pathways for generating NADPH and glutathione to suppress ROS. A detailed + understanding of the biochemical mechanisms by which cancer cells suppress + excess ROS may suggest new therapies for inducing synthetic lethality in tumors + that evolve in specific mutational backgrounds. Our research using human cancer + cell lines and genetically engineered mouse models suggests new approaches + for killing cancer cells by targeting metabolic pathways for ROS suppression + that allow cancer cells to survive. Citation Format: Lewis C. Cantley. PI + 3-kinase and cancer metabolism. [abstract]. In: Proceedings of the 107th Annual + Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New + Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract + nr SY12-01.", "venue": "", "year": 2016, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2016-07-15", "journal": {"volume": + "76", "name": "Cancer Research"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "f33f4df3c7f3c86bcd232dfeeec11c91364e1029", "externalIds": + {"PubMedCentral": "5047696", "MAG": "2735956876", "DOI": "10.1242/dmm.026856", + "CorpusId": 2906468, "PubMed": "27491070"}, "corpusId": 2906468, "publicationVenue": + {"id": "dbfaf49f-d95c-406a-96d9-3a357140a3a6", "name": "Disease Models & Mechanisms", + "type": "journal", "alternate_names": ["Dis Model Mech"], "issn": "1754-8403", + "url": "https://dmm.biologists.org/", "alternate_urls": ["http://dmm.biologists.org/"]}, + "url": "https://www.semanticscholar.org/paper/f33f4df3c7f3c86bcd232dfeeec11c91364e1029", + "title": "Seeking out the sweet spot in cancer therapeutics: an interview + with Lewis Cantley", "abstract": "Lewis C. Cantley, Director of the Sandra + and Edward Meyer Cancer Center at Weill Cornell Medicine, is a world leader + in cancer and metabolic disease research. His seminal discoveries have shed + light on the regulation of ion pumps and other transport proteins, insulin-mediated + regulation of glucose metabolism and the role of signal transduction networks + in cell transformation. At Tufts University in the 1980s, Lewis and his collaborators + unveiled and characterized the phosphoinositide 3-kinase (PI3K) signaling + pathway; a discovery that revolutionized the field of lipid signaling. In + this interview, he documents his journey from serendipitous discovery of the + pathway to determining its diverse physiological functions and role in cancer + \u2013 an incredible odyssey that has laid the groundwork for clinical trials + based on PI3K inhibitors. He also discusses the impact his early life had + in spurring a thirst to understand biological processes at the molecular level, + highlights how his multiple collaborations have helped in translating his + basic discoveries to the clinic and explains why eating a high-sugar diet + can be harmful. Ongoing studies in the Cantley lab are aimed at determining + the mechanistic underpinnings of pancreatic, colorectal, ovarian and breast + cancers, particularly the role of cellular metabolic pathways. The group has + recently shown, amongst other breakthroughs, that vitamin C could provide + a promising therapy for certain hard-to-treat cancers. Summary: We spoke to + Lewis Cantley about his career path and the story behind some of his key breakthroughs, + including discovery of the phosphoinositide 3-kinase signaling pathway and + insights into the role of dysregulated metabolism in cancer.", "venue": "Disease + Models & Mechanisms", "year": 2016, "referenceCount": 0, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2016-09-01", "journal": {"volume": "9", "pages": "911 + - 916", "name": "Disease Models & Mechanisms"}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "f39539f0f785bcfcbd8d51facfc870e941ec380a", + "externalIds": {"MAG": "2336310263", "PubMedCentral": "4848114", "DOI": "10.1038/ncb3341", + "CorpusId": 36807122, "PubMed": "27088857"}, "corpusId": 36807122, "publicationVenue": + {"id": "7d182b83-7d8d-43fb-9fd6-ae67fbafab20", "name": "Nature Cell Biology", + "type": "journal", "alternate_names": ["Nat Cell Biology"], "issn": "1465-7392", + "url": "http://www.nature.com/naturecellbiology", "alternate_urls": ["https://www.nature.com/ncb/"]}, + "url": "https://www.semanticscholar.org/paper/f39539f0f785bcfcbd8d51facfc870e941ec380a", + "title": "Glutathione biosynthesis is a metabolic vulnerability in PI3K/Akt-driven + breast cancer", "abstract": null, "venue": "Nature Cell Biology", "year": + 2016, "referenceCount": 44, "citationCount": 167, "influentialCitationCount": + 6, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4848114?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2016-03-16", "journal": {"volume": "18", "pages": "572 + - 578", "name": "Nature cell biology"}, "authors": [{"authorId": "4729701", + "name": "Evan C. Lien"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "49149990", "name": "Ashish Juvekar"}, {"authorId": "113164867", + "name": "Hai Hu"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "145751285", "name": "A. Toker"}]}, + {"paperId": "fa4c3f72ef670ee72a3beb5a8f2d1f4c96be3ba3", "externalIds": {"MAG": + "2508551534", "DOI": "10.1007/978-3-319-42118-6_3", "CorpusId": 26123083, + "PubMed": "27557534"}, "corpusId": 26123083, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/fa4c3f72ef670ee72a3beb5a8f2d1f4c96be3ba3", + "title": "Metabolic Reprogramming by the PI3K-Akt-mTOR Pathway in Cancer.", + "abstract": null, "venue": "Recent results in cancer research. Fortschritte + der Krebsforschung. Progres dans les recherches sur le cancer", "year": 2016, + "referenceCount": 200, "citationCount": 129, "influentialCitationCount": 1, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + null, "journal": {"volume": "207", "pages": "\n 39-72\n ", + "name": "Recent results in cancer research. Fortschritte der Krebsforschung. + Progres dans les recherches sur le cancer"}, "authors": [{"authorId": "4729701", + "name": "Evan C. Lien"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "049e6e417aa01258cc8a28cb244e3f7be7b023fd", + "externalIds": {"MAG": "2978051430", "DOI": "10.2210/pdb3x07/pdb", "CorpusId": + 210517195}, "corpusId": 210517195, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/049e6e417aa01258cc8a28cb244e3f7be7b023fd", + "title": "Crystal structure of PIP4KIIBETA N203A complex with AMP", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}], "publicationTypes": null, "publicationDate": + "2015-10-14", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "2775065", "name": "K. Takeuchi"}, {"authorId": "121709354", "name": "Y. Lo"}, + {"authorId": "49715313", "name": "K. Sumita"}, {"authorId": "5638813", "name": + "M. Senda"}, {"authorId": "49515406", "name": "Jumpei Terakawa"}, {"authorId": + "1485705386", "name": "A. Dimitoris"}, {"authorId": "2268976", "name": "J. + Locasale"}, {"authorId": "152671464", "name": "Mika Sasaki"}, {"authorId": + "6824343", "name": "H. Yoshino"}, {"authorId": "49891201", "name": "Y. Zhang"}, + {"authorId": "4049626", "name": "E. Kahoud"}, {"authorId": "91895026", "name": + "T. Takano"}, {"authorId": "10207871", "name": "T. Yokota"}, {"authorId": + "5542751", "name": "B. Emerling"}, {"authorId": "1394348007", "name": "J. + Asara"}, {"authorId": "47983250", "name": "T. Ishida"}, {"authorId": "144714771", + "name": "I. Shimada"}, {"authorId": "145457715", "name": "T. Daikoku"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "50162552", "name": "T. Senda"}, + {"authorId": "47742211", "name": "A. Sasaki"}]}, {"paperId": "0561d0105e31d38dc212b0f70664a702c4a47cc7", + "externalIds": {"MAG": "1960369368", "DOI": "10.1016/j.molonc.2015.04.014", + "CorpusId": 5236294, "PubMed": "26045339"}, "corpusId": 5236294, "publicationVenue": + {"id": "0f2158b1-4721-44a4-89ab-6cfc91eaca11", "name": "Molecular Oncology", + "type": "journal", "alternate_names": ["Mol Oncol"], "issn": "1574-7891", + "url": "http://febs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)1878-0261/", + "alternate_urls": ["http://www.moloncol.org/home"]}, "url": "https://www.semanticscholar.org/paper/0561d0105e31d38dc212b0f70664a702c4a47cc7", + "title": "PTEN loss is a context\u2010dependent outcome determinant in obese + and non\u2010obese endometrioid endometrial cancer patients", "abstract": + null, "venue": "Molecular Oncology", "year": 2015, "referenceCount": 55, "citationCount": + 46, "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": + {"url": "https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1016/j.molonc.2015.04.014", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2015-10-01", "journal": {"volume": "9", "name": "Molecular + Oncology"}, "authors": [{"authorId": "2974900", "name": "S. Westin"}, {"authorId": + "152983291", "name": "Z. Ju"}, {"authorId": "6416382", "name": "R. Broaddus"}, + {"authorId": "6534390", "name": "C. Krakstad"}, {"authorId": "2108996618", + "name": "Jane Li"}, {"authorId": "35508831", "name": "N. Pal"}, {"authorId": + "8500699", "name": "K. Lu"}, {"authorId": "3124983", "name": "R. Coleman"}, + {"authorId": "2030236", "name": "B. Hennessy"}, {"authorId": "4677205", "name": + "S. Klempner"}, {"authorId": "144323273", "name": "H. Werner"}, {"authorId": + "144568679", "name": "H. Salvesen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2241330", "name": "G. Mills"}, {"authorId": "6324437", "name": + "A. Myers"}]}, {"paperId": "06cdb74dc5e901b4aee2620b2ee8b98e05317b50", "externalIds": + {"MAG": "2588625478", "DOI": "10.1016/J.IJROBP.2015.07.120", "CorpusId": 79027350}, + "corpusId": 79027350, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/06cdb74dc5e901b4aee2620b2ee8b98e05317b50", + "title": "Inhibition of Phosphatidylinositol-5-Phosphate 4-Kinases (PI5P4K\u03b1 + and \u03b2) Inhibits Proliferation and Radiosensitizes Triple Negative Breast + Cancer Cells Harboring p53 Mutations", "abstract": null, "venue": "", "year": + 2015, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.redjournal.org/article/S0360301615008512/pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-11-01", "journal": {"volume": + "93", "name": "International Journal of Radiation Oncology Biology Physics"}, + "authors": [{"authorId": "2115865796", "name": "T. Yang"}, {"authorId": "152325571", + "name": "Diana G. Wang"}, {"authorId": "34187590", "name": "C. Pauli"}, {"authorId": + "31875049", "name": "Ryan Loughran"}, {"authorId": "2155396453", "name": "H. + Kim"}, {"authorId": "2262535", "name": "Tinghu Zhang"}, {"authorId": "48181912", + "name": "D. Annamalai"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1695518", "name": "S. Powell"}, {"authorId": "3977406", "name": "N. Gray"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "0a2b2a67b0b346a52c9f13535b03da8d9f50ee24", + "externalIds": {"MAG": "2174352319", "DOI": "10.1038/nsmb.3117", "CorpusId": + 987663, "PubMed": "26551075"}, "corpusId": 987663, "publicationVenue": null, + "url": "https://www.semanticscholar.org/paper/0a2b2a67b0b346a52c9f13535b03da8d9f50ee24", + "title": "EGF-receptor specificity for phosphotyrosine-primed substrates provides + signal integration with Src", "abstract": null, "venue": "Nature Structural + &Molecular Biology", "year": 2015, "referenceCount": 57, "citationCount": + 34, "influentialCitationCount": 4, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc4824005?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2015-12-01", "journal": {"volume": "22", "pages": "983-990", "name": "Nature + Structural &Molecular Biology"}, "authors": [{"authorId": "69874482", "name": + "M. Begley"}, {"authorId": "3555673", "name": "C. Yun"}, {"authorId": "7739224", + "name": "C. Gewinner"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "145916288", "name": "Jared L. Johnson"}, {"authorId": "2116662", "name": + "A. Coyle"}, {"authorId": "153402662", "name": "M. Eck"}, {"authorId": "6817362", + "name": "I. Apostolou"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "0b3a0ac2298c34306198ab8958851fde41bff1e8", "externalIds": {"MAG": + "2114861961", "DOI": "10.1158/0008-5472.CAN-14-2268", "CorpusId": 1680774, + "PubMed": "25511375"}, "corpusId": 1680774, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/0b3a0ac2298c34306198ab8958851fde41bff1e8", + "title": "Gain of glucose-independent growth upon metastasis of breast cancer + cells to the brain.", "abstract": "Breast cancer brain metastasis is resistant + to therapy and a particularly poor prognostic feature in patient survival. + Altered metabolism is a common feature of cancer cells, but little is known + as to what metabolic changes benefit breast cancer brain metastases. We found + that brain metastatic breast cancer cells evolved the ability to survive and + proliferate independent of glucose due to enhanced gluconeogenesis and oxidations + of glutamine and branched chain amino acids, which together sustain the nonoxidative + pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases + (FBP) in brain metastatic cells reduced their viability and improved the survival + of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain + metastases from human breast cancer patients expressed higher levels of FBP + and glycogen than the corresponding primary tumors. Together, our findings + identify a critical metabolic condition required to sustain brain metastasis + and suggest that targeting gluconeogenesis may help eradicate this deadly + feature in advanced breast cancer patients.", "venue": "Cancer Research", + "year": 2015, "referenceCount": 59, "citationCount": 115, "influentialCitationCount": + 6, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4315743?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2015-02-01", "journal": {"volume": "75 3", "pages": "\n 554-65\n ", + "name": "Cancer research"}, "authors": [{"authorId": "2136211075", "name": + "Jinyu Chen"}, {"authorId": "2110018995", "name": "Ho-Jeong Lee"}, {"authorId": + "74585917", "name": "Xuefeng Wu"}, {"authorId": "48605888", "name": "L. Huo"}, + {"authorId": "46876643", "name": "Sun-jin Kim"}, {"authorId": "2116558193", + "name": "Lei Xu"}, {"authorId": "47906499", "name": "Yan Wang"}, {"authorId": + "2326587", "name": "Junqin He"}, {"authorId": "4549367", "name": "L. Bollu"}, + {"authorId": "48807811", "name": "G. Gao"}, {"authorId": "2058372978", "name": + "Fei Su"}, {"authorId": "2061233933", "name": "James Briggs"}, {"authorId": + "2110961349", "name": "Xiaojing Liu"}, {"authorId": "1853856", "name": "T. + Melman"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "4191038", + "name": "I. Fidler"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2268976", "name": "J. Locasale"}, {"authorId": "46549654", "name": "Z. Weihua"}]}, + {"paperId": "176594e5304d63cccd19e57db36f70d54a118f1b", "externalIds": {"MAG": + "2978599975", "DOI": "10.2210/pdb3x01/pdb", "CorpusId": 210527426}, "corpusId": + 210527426, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/176594e5304d63cccd19e57db36f70d54a118f1b", + "title": "Crystal structure of PIP4KIIBETA complex with AMP", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-10-14", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2775065", "name": "K. Takeuchi"}, + {"authorId": "121709354", "name": "Y. Lo"}, {"authorId": "49715313", "name": + "K. Sumita"}, {"authorId": "5638813", "name": "M. Senda"}, {"authorId": "49515406", + "name": "Jumpei Terakawa"}, {"authorId": "1485705386", "name": "A. Dimitoris"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "152671464", + "name": "Mika Sasaki"}, {"authorId": "6824343", "name": "H. Yoshino"}, {"authorId": + "49891201", "name": "Y. Zhang"}, {"authorId": "4049626", "name": "E. Kahoud"}, + {"authorId": "91895026", "name": "T. Takano"}, {"authorId": "10207871", "name": + "T. Yokota"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1394348007", "name": "J. Asara"}, {"authorId": "47983250", "name": "T. Ishida"}, + {"authorId": "144714771", "name": "I. Shimada"}, {"authorId": "145457715", + "name": "T. Daikoku"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "50162552", "name": "T. Senda"}, {"authorId": "47742211", "name": "A. Sasaki"}]}, + {"paperId": "1de1e1380a6831478b0df4c641fe32e8c6bdb51e", "externalIds": {"MAG": + "2196075541", "DOI": "10.1158/2159-8290.CD-15-0068", "CorpusId": 1553760, + "PubMed": "26446169"}, "corpusId": 1553760, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/1de1e1380a6831478b0df4c641fe32e8c6bdb51e", + "title": "A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals + Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and + Metabolic Characteristics.", "abstract": "UNLABELLED\nSeeking to assess the + representative and instructive value of an engineered mouse model of pancreatic + neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and + compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors + could be classified into two distinctive subtypes, well-differentiated islet/insulinoma + tumors (IT) and poorly differentiated tumors associated with liver metastases, + dubbed metastasis-like primary (MLP). Human PanNETs were independently classified + into these same two subtypes, along with a third, specific gene mutation-enriched + subtype. The MLP subtypes in human and mouse were similar to liver metastases + in terms of miRNA and mRNA transcriptome profiles and signature genes. The + human/mouse MLP subtypes also similarly expressed genes known to regulate + early pancreas development, whereas the IT subtypes expressed genes characteristic + of mature islet cells, suggesting different tumorigenesis pathways. In addition, + these subtypes exhibit distinct metabolic profiles marked by differential + pyruvate metabolism, substantiating the significance of their separate identities.\n\n\nSIGNIFICANCE\nThis + study involves a comprehensive cross-species integrated analysis of multi-omics + profiles and histology to stratify PanNETs into subtypes with distinctive + characteristics. We provide support for the RIP1-TAG2 mouse model as representative + of its cognate human cancer with prospects to better understand PanNET heterogeneity + and consider future applications of personalized cancer therapy.", "venue": + "Cancer Discovery", "year": 2015, "referenceCount": 74, "citationCount": 123, + "influentialCitationCount": 9, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc4946251?pdf=render", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2015-10-07", "journal": {"volume": "5 12", "pages": "\n 1296-313\n ", + "name": "Cancer discovery"}, "authors": [{"authorId": "49973308", "name": + "A. Sadanandam"}, {"authorId": "38356613", "name": "S. Wullschleger"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "2555682", "name": "C. Gr\u00f6tzinger"}, + {"authorId": "6877885", "name": "S. Barbi"}, {"authorId": "29823932", "name": + "S. Bersani"}, {"authorId": "3892565", "name": "Jan L K\u00f6rner"}, {"authorId": + "116518204", "name": "Ismael Wafy"}, {"authorId": "4782975", "name": "A. Mafficini"}, + {"authorId": "3330807", "name": "R. Lawlor"}, {"authorId": "6643411", "name": + "M. Simbolo"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "3883634", + "name": "H. Bl\u00e4ker"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4406446", "name": "B. Wiedenmann"}, {"authorId": "143784645", + "name": "A. Scarpa"}, {"authorId": "6883889", "name": "D. Hanahan"}]}, {"paperId": + "23f6c5b2c9a747442b09880328e14ab800474b30", "externalIds": {"MAG": "2582692617", + "DOI": "10.1158/1078-0432.CCR-15-1846", "CorpusId": 207652755, "PubMed": "26429991"}, + "corpusId": 207652755, "publicationVenue": {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", + "name": "Clinical Cancer Research", "type": "journal", "alternate_names": + ["Clin Cancer Res"], "issn": "1078-0432", "url": "https://clincancerres.aacrjournals.org/", + "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/23f6c5b2c9a747442b09880328e14ab800474b30", + "title": "AACR Cancer Progress Report 2015", "abstract": "*These authors contributed + to the devlopment and review of this manuscript but are unable to endorse + the request for NIH funding.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nOn + Sept. 20, 2011, the American Association for Cancer Research (AACR) released + its inaugural AACR Cancer Progress Report to commemorate the", "venue": "Clinical + Cancer Research", "year": 2015, "referenceCount": 216, "citationCount": 28, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc5001568?pdf=render", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["Review"], "publicationDate": + "2015-10-01", "journal": {"volume": "21", "pages": "S1 - S128", "name": "Clinical + Cancer Research"}, "authors": [{"authorId": "144806171", "name": "J. Baselga"}, + {"authorId": "144952828", "name": "N. Bhardwaj"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "3572324", "name": "R. DeMatteo"}, {"authorId": + "4135978", "name": "R. DuBois"}, {"authorId": "48762531", "name": "M. Foti"}, + {"authorId": "4380527", "name": "S. Gapstur"}, {"authorId": "1890553", "name": + "W. Hahn"}, {"authorId": "4169821", "name": "L. Helman"}, {"authorId": "92266338", + "name": "R. Jensen"}, {"authorId": "143751246", "name": "E. Paskett"}, {"authorId": + "2984849", "name": "T. Lawrence"}, {"authorId": "3656125", "name": "S. Lutzker"}, + {"authorId": "143616557", "name": "E. Szabo"}]}, {"paperId": "2800b1f76a9c65e8df8c9f703869e9547c3c64a9", + "externalIds": {"PubMedCentral": "4721512", "MAG": "2173466127", "DOI": "10.1038/ng.3421", + "CorpusId": 13931286, "PubMed": "26482881"}, "corpusId": 13931286, "publicationVenue": + {"id": "bb27e645-e57c-42c3-bcbc-c7b443c58209", "name": "Nature Genetics", + "type": "journal", "alternate_names": ["Nat Genet"], "issn": "1061-4036", + "url": "http://www.nature.com/ng/", "alternate_urls": ["http://www.nature.com/ng/index.html"]}, + "url": "https://www.semanticscholar.org/paper/2800b1f76a9c65e8df8c9f703869e9547c3c64a9", + "title": "NRF2 regulates serine biosynthesis in non-small cell lung cancer", + "abstract": null, "venue": "Nature Genetics", "year": 2015, "referenceCount": + 32, "citationCount": 488, "influentialCitationCount": 26, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4721512?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2015-10-15", "journal": {"volume": + "47", "pages": "1475 - 1481", "name": "Nature genetics"}, "authors": [{"authorId": + "4772111", "name": "G. DeNicola"}, {"authorId": "4047142", "name": "Pei-Hsuan + Chen"}, {"authorId": "6424987", "name": "Edouard Mullarky"}, {"authorId": + "5467431", "name": "J. Sudderth"}, {"authorId": "3616375", "name": "Zeping + Hu"}, {"authorId": "144790190", "name": "David Wu"}, {"authorId": "2112388600", + "name": "Hao Tang"}, {"authorId": "145668114", "name": "Yang Xie"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "5305256", "name": "K. Huffman"}, + {"authorId": "46528860", "name": "I. Wistuba"}, {"authorId": "2996220", "name": + "J. Minna"}, {"authorId": "5834413", "name": "R. Deberardinis"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "2baef32a40ae7886157de933d7494df92f6f2a5b", + "externalIds": {"MAG": "2977458141", "DOI": "10.2210/pdb3wzz/pdb", "CorpusId": + 210514480}, "corpusId": 210514480, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/2baef32a40ae7886157de933d7494df92f6f2a5b", + "title": "Crystal structure of PIP4KIIBETA", "abstract": null, "venue": "", + "year": 2015, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Materials + Science"], "s2FieldsOfStudy": [{"category": "Materials Science", "source": + "external"}], "publicationTypes": null, "publicationDate": "2015-10-14", "journal": + {"volume": "", "name": ""}, "authors": [{"authorId": "2775065", "name": "K. + Takeuchi"}, {"authorId": "121709354", "name": "Y. Lo"}, {"authorId": "49715313", + "name": "K. Sumita"}, {"authorId": "5638813", "name": "M. Senda"}, {"authorId": + "49515406", "name": "Jumpei Terakawa"}, {"authorId": "1485705386", "name": + "A. Dimitoris"}, {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "152671464", "name": "Mika Sasaki"}, {"authorId": "6824343", "name": "H. Yoshino"}, + {"authorId": "49891201", "name": "Y. Zhang"}, {"authorId": "4049626", "name": + "E. Kahoud"}, {"authorId": "91895026", "name": "T. Takano"}, {"authorId": + "10207871", "name": "T. Yokota"}, {"authorId": "5542751", "name": "B. Emerling"}, + {"authorId": "1394348007", "name": "J. Asara"}, {"authorId": "47983250", "name": + "T. Ishida"}, {"authorId": "144714771", "name": "I. Shimada"}, {"authorId": + "145457715", "name": "T. Daikoku"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "50162552", "name": "T. Senda"}, {"authorId": "47742211", "name": + "A. Sasaki"}]}, {"paperId": "2f24eea2a2d8a409f3bc14c93aa5f0346681ec0c", "externalIds": + {"MAG": "2407334388", "DOI": "10.1158/1535-7163.TARG-15-C112", "CorpusId": + 88593949}, "corpusId": 88593949, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/2f24eea2a2d8a409f3bc14c93aa5f0346681ec0c", + "title": "Abstract C112: Cabozantinib eradicates advanced murine prostate + cancer by activating anti-tumor innate immunity", "abstract": "Several kinase + inhibitors targeting aberrant signaling pathways in tumor cells have been + deployed in cancer therapy. However, their impact on the tumor immune microenvironment + remains poorly understood. The tyrosine kinase inhibitor cabozantinib showed + striking responses in early phase clinical trials, particularly in cancer + patients with bone metastases. Here we show that cabozantinib rapidly eradicates + invasive, poorly-differentiated PTEN/p53 deficient murine prostate cancer. + This was associated with increased neutrophil chemotactic factor expression, + including CXCL12 and HMGB1 production by tumor cells, and robust infiltration + of neutrophils into the tumor. Critically, cabozantinib-induced tumor clearance + in mice was abolished by antibody-mediated granulocyte depletion or HMGB1 + neutralization or blockade of neutrophil chemotaxis with the CXCR4 inhibitor, + plerixafor. Collectively, these results demonstrate that cabozantinib triggers + neutrophil-mediated anti-tumor innate immune response that results in tumor + clearance. (Manuscript submitted to Science) Citation Format: Akash Patnaik, + Kenneth Swanson, Sabina Signoretti, Huihui Ye, Eva Csizmadia, Jesse Novak, + Marina Gehring, Katja Helenius, Athalia Pyzer, Laleh Montaser, Lily Wang, + Olivier Elemento, Elena Levantini, John Clohessy, John Asara, Kathleen Kelly, + Pier Paolo Pandolfi, Jacalyn Rosenblatt, David Avigan, Steven Balk, Lewis + Cantley. Cabozantinib eradicates advanced murine prostate cancer by activating + anti-tumor innate immunity. [abstract]. In: Proceedings of the AACR-NCI-EORTC + International Conference: Molecular Targets and Cancer Therapeutics; 2015 + Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl + 2):Abstract nr C112.", "venue": "", "year": 2015, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-12-01", "journal": {"volume": + "14", "name": "Molecular Cancer Therapeutics"}, "authors": [{"authorId": "40501341", + "name": "A. Patnaik"}, {"authorId": "6784962", "name": "K. Swanson"}, {"authorId": + "7505152", "name": "S. Signoretti"}, {"authorId": "3073381", "name": "Huihui + Ye"}, {"authorId": "4793517", "name": "E. Csizmadia"}, {"authorId": "50577147", + "name": "Jesse S. Novak"}, {"authorId": "33820964", "name": "M. Gehring"}, + {"authorId": "49804844", "name": "Katja Helenius"}, {"authorId": "15061933", + "name": "A. Pyzer"}, {"authorId": "49666064", "name": "L. Montaser"}, {"authorId": + "2117931332", "name": "Lily C. Wang"}, {"authorId": "150097652", "name": "O. + Elemento"}, {"authorId": "3768843", "name": "E. Levantini"}, {"authorId": + "4102988", "name": "J. Clohessy"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "145953924", "name": "K. Kelly"}, {"authorId": "4499580", "name": + "P. Pandolfi"}, {"authorId": "31499217", "name": "J. Rosenblatt"}, {"authorId": + "145881219", "name": "D. Avigan"}, {"authorId": "6189162", "name": "S. Balk"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "35c37182a716d5858bfcc80cbc29ee1d4e2c0181", + "externalIds": {"MAG": "2977581094", "DOI": "10.2210/pdb3x03/pdb", "CorpusId": + 210511560}, "corpusId": 210511560, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/35c37182a716d5858bfcc80cbc29ee1d4e2c0181", + "title": "Crystal structure of PIP4KIIBETA complex with AMPPNP", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-10-14", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2775065", "name": "K. Takeuchi"}, + {"authorId": "121709354", "name": "Y. Lo"}, {"authorId": "49715313", "name": + "K. Sumita"}, {"authorId": "5638813", "name": "M. Senda"}, {"authorId": "49515406", + "name": "Jumpei Terakawa"}, {"authorId": "1485705386", "name": "A. Dimitoris"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "152671464", + "name": "Mika Sasaki"}, {"authorId": "6824343", "name": "H. Yoshino"}, {"authorId": + "49891201", "name": "Y. Zhang"}, {"authorId": "4049626", "name": "E. Kahoud"}, + {"authorId": "91895026", "name": "T. Takano"}, {"authorId": "10207871", "name": + "T. Yokota"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1394348007", "name": "J. Asara"}, {"authorId": "47983250", "name": "T. Ishida"}, + {"authorId": "144714771", "name": "I. Shimada"}, {"authorId": "145457715", + "name": "T. Daikoku"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "50162552", "name": "T. Senda"}, {"authorId": "47742211", "name": "A. Sasaki"}]}, + {"paperId": "389bf670061ce9a4739177ef80c62e6ff12bccd9", "externalIds": {"MAG": + "1661254177", "DOI": "10.1158/1538-7445.AM2015-CT324", "CorpusId": 70619331}, + "corpusId": 70619331, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/389bf670061ce9a4739177ef80c62e6ff12bccd9", + "title": "Abstract CT324: Phase I of oral BKM120 or BYL719 and olaparib for + high-grade serous ovarian cancer or triple-negative breast cancer: Final results + of the BKM120 plus olaparib cohort", "abstract": "Background: Similarities + exist between high grade serous ovarian cancer (HGSC) and triple negative + breast cancer (TNBC); both often have gBRCA mutations, are sensitive to platinum + agents, and have high copy number alterations per the TCGA. Preclinical data + for both BKM120/olaparib and BYL719/olaparib combinations showed synergistic + efficacy. These data served as the rationale for this study in pts with either + recurrent HGSC or TNBC. The phase I study of BKM120 and olaparib has been + completed, and the phase I study of BYL719 and olaparib is currently in dose + escalation (NCT01623349). Methods: This study has a 3 + 3 design, escalating + dose levels (DL) if 0/3 or 1/6 pts have a dose limiting toxicity (DLT) during + the first cycle (1st 28 days). Objectives were to determine the MTD and RP2D + of daily oral olaparib (tablet formulation) and BKM120, assess toxicities, + activity of this combination, and PK profiles of both drugs. Planned translational + endpts include PI3kinase pathway effects, BRCA1 immunostaining/methylation, + IL-8/circulating DNA levels, and somatic mutations in BRCA1/2 using FFPE tissue. + Eligibility included: recurrent TNBC or HGSC or any histology of ovarian cancer + (OvCa) or breast cancer (BrCa) with presence of a gBRCAmut, PS 0-1, and measurable/evaluable + cancer. Prior PARP inhibitor use was allowed. Results: 46 pts to date have + received study drugs as part of the ph1 dose escalation of BKM120/olaparib + (12 pts w/BrCa and 34 pts w/OvCa). 35 have known gBRCAm. Dosing started at + DL1 (BKM120 60 mg and olaparib 100 mg BID); 2 DLTs were observed (1 gr 3 LFTs + and 1 gr 3 hyperglycemia). A lower dose (-1) was pursued followed by re-escalation; + MTD is BKM120 50 mg and olaparib 300 mg BID. Toxicities that defined DLTs + included CNS toxicities (gr 3 depression) and grade 3 LFTs, early in cycle + 2 (DL6). At the MTD of BKM120/olaparib, 11 pts with OvCa and 12 pts w BrCa + were enrolled into a dose expansion cohort (DEC). Evidence of clinical benefit + by RECIST 1.1 was observed on all DL9s and in the DEC\u2019s, in pts with + a gBRCApos as well as gBRCAwt. AEs seen were compatible with AE profile of + BKM120 and olaparib. Conclusions: Combined BKM120 and olaparib is feasible, + and evidence of clinical benefit was seen at all DL9s both in gBRCApos and + gBRCAwt pts. Toxicities that defined DLTs included CNS toxicities and LFT + abnormalities. Clinical trial information: NCT01623349. Citation Format: Ursula + A. Matulonis, Gerburg Wulf, William Barry, Michael Birrer, Shannon Westin, + Tatum Spagnoletti, Katherine Bell-McGuinn, Elizabeth Obermayer, Christin Whalen, + Carol Aghajanian, David Solit, Gordon Mills, Lewis Cantley, Eric Winer. Phase + I of oral BKM120 or BYL719 and olaparib for high-grade serous ovarian cancer + or triple-negative breast cancer: Final results of the BKM120 plus olaparib + cohort. [abstract]. In: Proceedings of the 106th Annual Meeting of the American + Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia + (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT324. doi:10.1158/1538-7445.AM2015-CT324", + "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 22, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2015-08-01", "journal": {"volume": "75", "name": "Cancer Research"}, "authors": + [{"authorId": "6927295", "name": "U. Matulonis"}, {"authorId": "31554501", + "name": "G. Wulf"}, {"authorId": "2774170", "name": "William H. Barry"}, {"authorId": + "2167106", "name": "M. Birrer"}, {"authorId": "2974900", "name": "S. Westin"}, + {"authorId": "15372310", "name": "T. Spagnoletti"}, {"authorId": "1397923721", + "name": "K. Bell-McGuinn"}, {"authorId": "12793341", "name": "E. Obermayer"}, + {"authorId": "122974814", "name": "C. Whalen"}, {"authorId": "6128162", "name": + "C. Aghajanian"}, {"authorId": "2344124", "name": "D. Solit"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2369378", "name": "E. Winer"}]}, {"paperId": "42c3e1bc8eddec3d0c1e7d8794521bbbb6faf89e", + "externalIds": {"MAG": "2144542772", "DOI": "10.1126/science.aaa5004", "CorpusId": + 206634814, "PubMed": "26541605"}, "corpusId": 206634814, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/42c3e1bc8eddec3d0c1e7d8794521bbbb6faf89e", + "title": "Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer + cells by targeting GAPDH", "abstract": "Getting all stressed out by vitamin + C Few experimental cancer therapies have incited as much debate as vitamin + C. Yet the mechanistic effect of vitamin C on cancer cells is still poorly + understood. Yun et al. studied human colorectal cancer cells with KRAS or + BRAF mutations and found that they \u201chandle\u201d vitamin C in a different + way than other cells, ultimately to their detriment (see the Perspective by + Reczek and Chandel). Because a certain receptor is up-regulated in the mutant + cells, they take up the oxidized form of vitamin C (dehydroascorbate). This + leads to oxidative stress, inactivation of a glycolytic enzyme required by + the mutant cells for growth, and finally cell death. Whether the selective + toxicity of vitamin C to these mutant cells can be exploited therapeutically + remains unclear. Science, this issue p. 1391; see also p. 1317 Cancer cells + with certain mutations take up the oxidized form of vitamin C, which fatally + disrupts their metabolism. [Also see Perspective by Reczek and Chandel] More + than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations + and are often refractory to approved targeted therapies. We found that cultured + human CRC cells harboring KRAS or BRAF mutations are selectively killed when + exposed to high levels of vitamin C. This effect is due to increased uptake + of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose + transporter. Increased DHA uptake causes oxidative stress as intracellular + DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen + species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase + (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells + leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type + cells. High-dose vitamin C impairs tumor growth in Apc/KrasG12D mutant mice. + These results provide a mechanistic rationale for exploring the therapeutic + use of vitamin C for CRCs with KRAS or BRAF mutations.", "venue": "Science", + "year": 2015, "referenceCount": 47, "citationCount": 627, "influentialCitationCount": + 41, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4778961?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2015-12-11", "journal": {"volume": + "350", "pages": "1391 - 1396", "name": "Science"}, "authors": [{"authorId": + "40164091", "name": "Jihye Yun"}, {"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "7434113", "name": "Changyuan Lu"}, {"authorId": + "7881810", "name": "Kaitlyn Bosch"}, {"authorId": "8391227", "name": "A. Kavalier"}, + {"authorId": "6991355", "name": "Keith D. Rivera"}, {"authorId": "145864068", + "name": "J. Roper"}, {"authorId": "4865028", "name": "I. I. C. Chio"}, {"authorId": + "1786519", "name": "Eugenia G. Giannopoulou"}, {"authorId": "1907762", "name": + "C. Rago"}, {"authorId": "145927271", "name": "A. Muley"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "5056578", "name": "J. Paik"}, {"authorId": + "150097652", "name": "O. Elemento"}, {"authorId": "49864822", "name": "Zhengming + Chen"}, {"authorId": "2249559", "name": "D. Pappin"}, {"authorId": "3918769", + "name": "L. Dow"}, {"authorId": "144798543", "name": "N. Papadopoulos"}, {"authorId": + "5769141", "name": "S. Gross"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "4456c9cd5f347c9a5e3a19518fb0ffe051bd8c8c", "externalIds": {"MAG": + "2566492858", "DOI": "10.1158/1538-7445.AM2015-5497", "CorpusId": 78941665}, + "corpusId": 78941665, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4456c9cd5f347c9a5e3a19518fb0ffe051bd8c8c", + "title": "Abstract 5497: Cabozantinib eradicatesde novocastrate-resistant + PTEN/p53 deficient murine prostate cancer via activation of neutrophil-mediated + anti-tumor innate immunity", "abstract": "The majority of kinase inhibitors + in cancer clinical trials have been evaluated in the context of cell autonomous + induction of apoptosis. However, apoptosis can result in protumorigenic immunosuppression, + which limits the durability of an anti-tumor response. Recent clinical trial + data shows striking clinical and radiographic responses with kinase inhibitor + cabozantinib (XL-184) in metastatic solid tumors, particularly in the context + of bone metastases. However, the mechanism responsible for this robust antitumor + response remain unknown. Here we show that cabozantinib eradicates poorly + differentiated invasive cancer that develop in the context of prostate-specific + PTEN and p53 loss, respectively, within 48 hours of cabozantinib treatment. + This rapid tumor clearance was temporally associated with infiltration of + mature polymorphonuclear leukocytes into the tumor bed. These anti-tumor effects + of cabozantinib appear to be MET-independent, since the MET inhibitor PF-04217903 + did not phenocopy the effects of cabozantinib in the prostate-specific PTEN/p53 + deficient mouse model in vivo. Unexpectedly, in vitro treatment of PTEN/p53 + deficient cell lines derived from murine tumors showed insignificant apoptosis, + but robust extracellular release of HMGB1, a neutrophil chemoattractant, and + marker of immunogenic cell death. To elucidate the relevance of an immunogenic + anti-tumor mechanism in vivo, we performed RNA-seq profiling and quantitative + RT-PCR analysis, which showed an acute increase in anti-tumor inflammatory + cytokine gene expression signature and neutrophil activation/chemotaxis markers + following acute cabozantinib treatment. Critically, blockade of neutrophil + chemotaxis/trafficking with dexamethasone or depletion with anti-Ly6G antibody, + reversed the effects of cabozantinib towards eradication of advanced PTEN/p53 + deficient tumors. Finally, cytokine array profiling of supernatant from bone + marrow metastases from castrate-resistant prostate cancer patients showed + increased neutrophil markers and decreased IL-6 levels within the bone microenvironment + following 6 weeks of cabozantinib treatment., thus polarizing the neutrophils + into\u201d N1\u201d effector cells. Collectively, these results shed light + on a novel anti-tumor immunogenic mechanism for cabozantinib within the tumor + microenvironment of PTEN/p53 deficient tumors, which unleashes a profound + innate anti-tumor immune response. These findings suggest the possibility + of combination therapies of cabozantinib with T-cell checkpoint blockade or + vaccine-based approaches, to augment immunologic responses in advanced cancers. + Citation Format: Akash Patnaik, Kenneth Swanson, Katja Helenius, Thornley + Thomas, Athalia Pyzer, Vilmosne Csizmadia, Sabina Signoretti, Todd Morgan, + Yugang Wang, Olivier Elemento, Lily Wang, Elena Levantini, John Clohessy, + John Asara, David Smith, Jacalyn Rosenblatt, David Avigan, Steven Balk, Lewis + Cantley. Cabozantinib eradicates de novo castrate-resistant PTEN/p53 deficient + murine prostate cancer via activation of neutrophil-mediated anti-tumor innate + immunity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American + Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia + (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5497. doi:10.1158/1538-7445.AM2015-5497", + "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 2, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2015-08-01", "journal": {"volume": "75", "pages": "5497-5497", "name": "Cancer + Research"}, "authors": [{"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "6784962", "name": "K. Swanson"}, {"authorId": "49804844", "name": "Katja + Helenius"}, {"authorId": "82258692", "name": "T. Thomas"}, {"authorId": "15061933", + "name": "A. Pyzer"}, {"authorId": "5460409", "name": "V. Csizmadia"}, {"authorId": + "7505152", "name": "S. Signoretti"}, {"authorId": "74997355", "name": "T. + Morgan"}, {"authorId": "49416325", "name": "Yugang Wang"}, {"authorId": "150097652", + "name": "O. Elemento"}, {"authorId": "2117931332", "name": "Lily C. Wang"}, + {"authorId": "3768843", "name": "E. Levantini"}, {"authorId": "4102988", "name": + "J. Clohessy"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "2153150772", "name": "David J. Smith"}, {"authorId": "31499217", "name": + "J. Rosenblatt"}, {"authorId": "145881219", "name": "D. Avigan"}, {"authorId": + "6189162", "name": "S. Balk"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "52dd7ea48b3427ae01ab83d0fa0ffad76c87c8ef", "externalIds": {"MAG": + "2978599022", "DOI": "10.2210/pdb3x0b/pdb", "CorpusId": 210524079}, "corpusId": + 210524079, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/52dd7ea48b3427ae01ab83d0fa0ffad76c87c8ef", + "title": "Crystal structure of PIP4KIIBETA I368A complex with AMP", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-10-14", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2775065", "name": "K. Takeuchi"}, + {"authorId": "121709354", "name": "Y. Lo"}, {"authorId": "49715313", "name": + "K. Sumita"}, {"authorId": "5638813", "name": "M. Senda"}, {"authorId": "49515406", + "name": "Jumpei Terakawa"}, {"authorId": "1485705386", "name": "A. Dimitoris"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "152671464", + "name": "Mika Sasaki"}, {"authorId": "6824343", "name": "H. Yoshino"}, {"authorId": + "49891201", "name": "Y. Zhang"}, {"authorId": "4049626", "name": "E. Kahoud"}, + {"authorId": "91895026", "name": "T. Takano"}, {"authorId": "10207871", "name": + "T. Yokota"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1394348007", "name": "J. Asara"}, {"authorId": "47983250", "name": "T. Ishida"}, + {"authorId": "144714771", "name": "I. Shimada"}, {"authorId": "145457715", + "name": "T. Daikoku"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "50162552", "name": "T. Senda"}, {"authorId": "47742211", "name": "A. Sasaki"}]}, + {"paperId": "57b3c45c5546a74e4591be8bc4df1079671b360f", "externalIds": {"MAG": + "1804602290", "DOI": "10.1016/j.tcb.2015.06.002", "CorpusId": 12240195, "PubMed": + "26159692"}, "corpusId": 12240195, "publicationVenue": {"id": "81cf38b2-9175-4415-aea1-d852b2702de3", + "name": "Trends in Cell Biology", "type": "journal", "alternate_names": ["Trends + Cell Biology"], "issn": "0962-8924", "url": "https://www.cell.com/trends/cell-biology/home", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/09628924"]}, + "url": "https://www.semanticscholar.org/paper/57b3c45c5546a74e4591be8bc4df1079671b360f", + "title": "Regulation of mTORC1 by PI3K signaling.", "abstract": null, "venue": + "Trends in Cell Biology", "year": 2015, "referenceCount": 154, "citationCount": + 532, "influentialCitationCount": 27, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc4734635?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2015-09-01", "journal": {"volume": + "25 9", "pages": "\n 545-55\n ", "name": "Trends in cell biology"}, + "authors": [{"authorId": "7449887", "name": "Christian C. Dibble"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "623115c5a64301e8723c66061aff2975dddf9638", + "externalIds": {"CorpusId": 16515423}, "corpusId": 16515423, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/623115c5a64301e8723c66061aff2975dddf9638", + "title": "Active Pin 1 is a key target of all-trans retinoic acid in acute + promyelocytic leukemia and breast cancer", "abstract": "A common key regulator + of oncogenic signaling pathways in multiple tumor types is the unique isomerase + Pin1. However, available Pin1 inhibitors lack the required specificity and + potency. Using mechanism-based screening, here we find that all-trans retinoic + acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered + the first example of targeted therapy in cancer, but its drug target remains + elusive--inhibits and degrades active Pin1 selectively in cancer cells by + directly binding to the substrate phosphateand proline-binding pockets in + the Pin1 active site. ATRA-induced Pin1 ablation degrades the fusion oncogene + PML-RAR\u03b1 and treats APL in cell and animal models and human patients. + ATRA-induced Pin1 ablation also inhibits triple negative breast cancer cell + growth in human cells and in animal models by acting on many Pin1 substrate + oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple + Pin1regulated cancer-driving pathways, an attractive property for treating + aggressive and drug-resistant tumors. Targeted therapy has changed cancer + treatment, but blocking a single pathway is often ineffective against solid + tumors, especially aggressive or drug-resistant ones due to activation of + redundant and/or alternative oncogenic pathways1. Thus a major challenge remains + how to block the multiple cancer-driving pathways simultaneously. A common + and central signaling mechanism in oncogenic pathways is proline-directed + phosphorylation (pSer/Thr-Pro)2. Numerous oncogenes and tumor suppressors + are either directly regulated by such phosphorylation (Supplementary Fig. + 1) and/or trigger signal pathways involving such phosphorylation2,3. Notably, + the same kinases often phosphorylate both oncogenes and tumor suppressors + to control their function. The prolyl isomerase (PPIase) Pin1 plays a critical + role in coordinating these multiple phosphorylation events to oncogenesis2,3. + Proline uniquely adopts cis and trans conformations, and their isomerization + is catalyzed by PPIases4 including the unique PPIase Pin12,5,6. Using its + WW domain, Pin1 binds to specific pSer/Thr-Pro motif(s), where its PPIase + domain catalyzes cis-trans isomerization of certain pSer/Thr-Pro motifs5, + which can be detected by cis and trans-specific antibodies6. Pin1 is commonly + overexpressed and/or activated in human cancers, which correlates with poor + outcomes3,7. In contrast, the Pin1 polymorphisms that lower Pin1 are associated + with reduced cancer risk8. Moreover, Pin1 deficiency in mice prevents tumorigenesis, + even that induced by activated oncogenes such as HER2 or Ras9, whereas Pin1 + overexpression disrupts cell cycle coordination leading to centrosome amplification, + chromosome instability and cancer development in cell and animal models of + breast cancer10. Pin1 activates at least 32 oncogenes and growth-promoting + proteins, and inactivates at least 19 tumor suppressors and growth-inhibiting + proteins2,3,11\u201320 (Supplementary Fig. 1). Thus, Pin1 can amplify oncogenic + pathways by simultaneously activating oncogenes and inactivating tumor suppressors. + Pin1 also plays a fundamental role in driving expansion and tumorigenesis + of cancer stem cells21\u201323, a major source of cancer resistance1. These + results suggest that Pin1 inhibitors could have the unique and desirable ability + to block multiple cancer-driving pathways as well as inhibit cancer stem cells + at the same time2,3,24, especially given that Pin1 KO mice develop normally + without obvious defects for an extended period of time25,26. Wei et al. Page + 2 Nat Med. Author manuscript; available in PMC 2015 November 01. A uhor M + anscript", "venue": "", "year": 2015, "referenceCount": 79, "citationCount": + 33, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "2017228", + "name": "Shuo Wei"}, {"authorId": "4436537", "name": "S. Kozono"}, {"authorId": + "48851123", "name": "L. Kats"}, {"authorId": "5885055", "name": "Morris Nechama"}, + {"authorId": "2108677453", "name": "Wenzong Li"}, {"authorId": "6708693", + "name": "J. Guarnerio"}, {"authorId": "49448597", "name": "Man-Li Luo"}, {"authorId": + "49529179", "name": "M. You"}, {"authorId": "33596659", "name": "Yandan Yao"}, + {"authorId": "5391279", "name": "A. Kondo"}, {"authorId": "113164867", "name": + "Hai Hu"}, {"authorId": "50415355", "name": "Gunes Bozkurt"}, {"authorId": + "6764358", "name": "N. Moerke"}, {"authorId": "87035236", "name": "S. Cao"}, + {"authorId": "49641019", "name": "M. Reschke"}, {"authorId": "120897015", + "name": "Chun-Hau Chen"}, {"authorId": "144046525", "name": "E. Rego"}, {"authorId": + "35594804", "name": "F. Lo\u2010Coco"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "145569223", "name": "T. Lee"}, {"authorId": "144663176", + "name": "Hao Wu"}, {"authorId": "2152820510", "name": "Yan Zhang"}, {"authorId": + "4499580", "name": "P. Pandolfi"}, {"authorId": "1409650665", "name": "Xiao + Zhen Zhou"}, {"authorId": "1715537", "name": "K. Lu"}]}, {"paperId": "6777312c8818dd4002437859cf38362a1b281a36", + "externalIds": {"MAG": "2258601828", "DOI": "10.1158/1538-8514.PI3K14-IA21", + "CorpusId": 87431236}, "corpusId": 87431236, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/6777312c8818dd4002437859cf38362a1b281a36", + "title": "Abstract IA21: Combination treatments that include PI3K-inhibitors + for the treatment of triple-negative breast cancer", "abstract": "Alterations + in the PI3K pathway are highly prevalent in triple-negative breast and high + grade ovarian cancer, including BRCA1- and BRCA2-related disease. On the cellular + level, loss of BRCA1 increases genomic instability and reliance on single + strand break repair, hence creating an opportunity to treat BRCA-related TNBC + or OC with PARP-inhibitors. In addition, loss of BRCA1 and/or p53 lead to + relaxation of negative feed-back loops in mitogenic signaling, resulting in + highly proliferative malignancies. For these reasons PARP-inhibitor Olaparib + and PI3K-inhibitor NVP-BKM120 were tested in combination and found to be synergistic + in mouse models of BRCA1-related BC. Surprisingly, PI3K-inhibition enhanced + a DNA damage phenotype, caused by a profound decrease in DNA synthesis that + could be observed after treatment with NVP-BKM120 in vivo and in vitro. The + decrease in DNA synthesis was due to reduced Nucleoside synthesis resulting + from a block in glycolysis that led to a drop in flux through the non-oxidative + pentose phosphate pathway. In a preclinical mouse model (K14-Cre BRCA1f/fp53f/f), + the combination of NVP-BKM120 and Olaparib could induce complete remissions, + while PI3K-inhibitor alone marginally slowed disease progression and PARP-inhibitor + alone stabilized the disease. This concept was translated into a clinical + trial: BKM120/Olaparib for Triple Negative Breast Cancer or High Grade Serous + Ovarian Cancer (NCT01623349; PI: Ursula Matulonis). Dose escalation for this + study and accrual to an extension cohort at the MTD (NVP-BKM120 50 mg once + a day in combination with Olaparib 300 mg twice a day) have been completed + and a second dose escalation arm with NVP-BYL719 and Olaparib is ongoing. + Citation Format: Gerburg M. Wulf, Ashish Juvekar, Costas M. Lyssiotis, Hai + Hu, Kim Baek, Sina Yadegarynia, Ralph Scully, Eric Winer, John Asara, Lewis + C. Cantley, Ursula Matulonis. Combination treatments that include PI3K-inhibitors + for the treatment of triple-negative breast cancer. [abstract]. In: Proceedings + of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; + Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther + 2015;14(7 Suppl):Abstract nr IA21.", "venue": "", "year": 2015, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-07-01", "journal": {"volume": + "14", "name": "Molecular Cancer Therapeutics"}, "authors": [{"authorId": "31554501", + "name": "G. Wulf"}, {"authorId": "49149990", "name": "Ashish Juvekar"}, {"authorId": + "88857753", "name": "Costas Lyssiotis"}, {"authorId": "113164867", "name": + "Hai Hu"}, {"authorId": "2061486079", "name": "K. Baek"}, {"authorId": "3893473", + "name": "S. Yadegarynia"}, {"authorId": "143905392", "name": "R. Scully"}, + {"authorId": "2369378", "name": "E. Winer"}, {"authorId": "3028470", "name": + "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6927295", + "name": "U. Matulonis"}]}, {"paperId": "6a6362bab18ab43adc01735f4e46288144accc7a", + "externalIds": {"MAG": "2978623456", "DOI": "10.2210/pdb3x09/pdb", "CorpusId": + 210527306}, "corpusId": 210527306, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/6a6362bab18ab43adc01735f4e46288144accc7a", + "title": "Crystal structure of PIP4KIIBETA F205L complex with AMP", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-10-14", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2775065", "name": "K. Takeuchi"}, + {"authorId": "121709354", "name": "Y. Lo"}, {"authorId": "49715313", "name": + "K. Sumita"}, {"authorId": "5638813", "name": "M. Senda"}, {"authorId": "49515406", + "name": "Jumpei Terakawa"}, {"authorId": "1485705386", "name": "A. Dimitoris"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "152671464", + "name": "Mika Sasaki"}, {"authorId": "6824343", "name": "H. Yoshino"}, {"authorId": + "49891201", "name": "Y. Zhang"}, {"authorId": "4049626", "name": "E. Kahoud"}, + {"authorId": "91895026", "name": "T. Takano"}, {"authorId": "10207871", "name": + "T. Yokota"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1394348007", "name": "J. Asara"}, {"authorId": "47983250", "name": "T. Ishida"}, + {"authorId": "144714771", "name": "I. Shimada"}, {"authorId": "145457715", + "name": "T. Daikoku"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "50162552", "name": "T. Senda"}, {"authorId": "47742211", "name": "A. Sasaki"}]}, + {"paperId": "6d6a8e5e03300e6af1fb4b2d66b87d93c66f95c8", "externalIds": {"MAG": + "2617270873", "DOI": "10.1016/J.CELL.2015.01.021", "CorpusId": 203871558}, + "corpusId": 203871558, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/6d6a8e5e03300e6af1fb4b2d66b87d93c66f95c8", + "title": "Erratum: Acetate fuels the cancer engine (Cell (2014) 159 (1492-1494))", + "abstract": null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.cell.com/article/S0092867415000641/pdf", "status": null}, "fieldsOfStudy": + ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Engineering", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2015-01-29", "journal": {"volume": "160", "name": + "Cell"}, "authors": [{"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "7007ac13c0b4ed5f7440f665580185b6acfc51bb", + "externalIds": {"MAG": "2291598966", "DOI": "10.1007/978-4-431-55651-0_1", + "CorpusId": 87929585}, "corpusId": 87929585, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/7007ac13c0b4ed5f7440f665580185b6acfc51bb", + "title": "Diverting Glycolysis to Combat Oxidative Stress", "abstract": null, + "venue": "", "year": 2015, "referenceCount": 133, "citationCount": 116, "influentialCitationCount": + 8, "isOpenAccess": true, "openAccessPdf": {"url": "https://link.springer.com/content/pdf/10.1007%2F978-4-431-55651-0_1.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "pages": "3-23", "name": ""}, "authors": [{"authorId": "6424987", "name": + "Edouard Mullarky"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "7c1c5b912b1a4f7ae26daa414416dc85476dab16", "externalIds": {"MAG": "2493079089", + "DOI": "10.1158/1538-7445.AM2015-2636", "CorpusId": 78503266}, "corpusId": + 78503266, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7c1c5b912b1a4f7ae26daa414416dc85476dab16", + "title": "Abstract 2636: Myc vs. Akt therapy in RapidCap, a GEM model for + metastatic prostate cancer", "abstract": "Metastasis is a major driver of + mortality and morbidity in prostate cancer, the most common cancer type in + men and the second leading cause of cancer-related deaths in the western world. + To recapitulate the process in genetically engineered mice, we have developed + the RapidCaP system, which uses prostate-directed viral infection to trigger + focal loss of Pten and Trp53. The system provides a powerful platform for + identification and validation of candidate driver genes and for efficient + testing of novel therapeutics. Using this approach, we have recently identified + Myc as a critical, spontaneously activated driver in Pten-negative metastatic + prostate cancer. In agreement, our previous trials indicated that the Myc-suppressing + Brd4 inhibitor JQ1 is ineffective towards primary disease, but causes metastatic + regression. Mechanistically, this specificity correlates with the switch from + Akt-driven primary to Myc-driven metastatic disease. \nIntriguingly, however, + advanced metastases in RapidCaP do not express the androgen receptor, in spite + of being of epithelial origin as shown by the Nkx3.1 prostate marker. As a + consequence, metastatic disease often shows little to no response to castration + therapy and invariably results in lethal disease. Therefore, we will discuss + how, when and why targeting of Myc using JQ1 and the PI 3-Kinase pathway using + NVP-BKM120 are best used to treat naive or castration-resistant metastatic + disease.", "venue": "", "year": 2015, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2015-08-01", "journal": {"volume": "75", "pages": "2636-2636", + "name": "Cancer Research"}, "authors": [{"authorId": "47270173", "name": "C. + Stahlhut"}, {"authorId": "10426666", "name": "Kaitlin Watrud"}, {"authorId": + "15976560", "name": "A. Ambrico"}, {"authorId": "4485082", "name": "Hyejin + Cho"}, {"authorId": "2117931332", "name": "Lily C. Wang"}, {"authorId": "145752082", + "name": "J. Qi"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3685746", "name": "J. Bradner"}, {"authorId": "4603490", "name": "L. Trotman"}]}, + {"paperId": "88eaaaffb83dc4c7fba09fc75af7fe9be27383fa", "externalIds": {"MAG": + "1469597457", "DOI": "10.1158/1538-7445.AM2015-CT232", "CorpusId": 70940740}, + "corpusId": 70940740, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/88eaaaffb83dc4c7fba09fc75af7fe9be27383fa", + "title": "Abstract CT232: SU2C Phase Ib study of the PI3K-alpha inhibitor + BYL719 (alpelisib) with letrozole in ER+/HER2-metastatic breast cancer", "abstract": + "Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, + PA\n\nBackground: Mutations in PIK3CA, the gene encoding the p110\u03b1 subunit + of PI3K, have been associated with antiestrogen resistance in ER+ BC. In general, + antiestrogen-resistant cancers retain ER and responsiveness to estradiol. + This suggests that treatment of ER+ BC with PI3K inhibitors should also include + antiestrogens.\n\nMethods: We conducted a phase Ib 3+3 dose escalation trial + of letrozole (2.5 mg/day) with the PI3K\u03b1 inhibitor BYL719 in post-menopausal + patients (pts) with ER+/HER2- metastatic breast cancer (MBC) refractory to + previous endocrine therapy. BYL719 doses ranged from 300-400 mg/daily. Treatment + continued until unacceptable toxicity or disease progression. Disease was + assessed every 2 months. PIK3CA mutation status was determined by SNaPshot + or targeted next generation sequencing (NGS) in all patients\u2019 tumors.\n\nResults: + Twenty-six pts were accrued; all patients were refractory to endocrine therapies + in the metastatic setting, 18 had prior aromatase inhibitor (AI) therapy in + their first or second-line MBC treatment. Median age was 53 years (31-72); + 76% of pts had bone and 61% had visceral metastases; 50% of pts had a somatic + PIK3CA hotspot mutation. Toxicities are summarized in Table 1. Rash was the + dose limiting toxicity* at 350 mg/day. Of the 5 pts with a partial response, + 3 (60%) had a PI3KCA mutation, 6/9 pts (67%) that were on treatment for \u22656 + months; 3/6 pts (50%) that were on treatment for \u226512 months and 4/6 pts + (67%) that are still on study (range 11 - 19 months) had a PI3KCA mutation.\n\nDiscussion: + The combination of letrozole/ BYL719 is safe and tolerable in pts with AI-refractory + ER+/HER2-negative MBC. The MTD and recommended dose for phase II trials of + BYL719 in combination with letrozole was 300 mg/day. Rash and hyperglycemia + were observed at this dose, suggesting drug-induced inhibition of PI3K. Pts + with PIK3CA-mutant tumors appeared to derive better clinical benefit, although + activity of the combination was also seen in patients with PIK3CA-wild type + cancers. Additional NGS of >300 cancer genes and their correlation with clinical + response will be updated at the meeting. Clinical trial information: [NCT01791478][1].\n\n| + Adverse Events (% by Grade) |\n|:---------------------------:| --------------- + |\n| Toxicity | 300 mg (N = 20) | 300 mg (N = 20) | | 350 mg (N = 6) | 350 + mg (N = 6) | |\n| | % by Grade | % by Grade | % Total | % by Grade | % by + Grade | % Total |\n| | 2 | 3 | | 2 | 3 | |\n| Hyperglycemia | 18 | 12 | 56 + | 20 | 20 | 70 |\n| Diarrhea | 12 | 12 | 81 | 10 | | 50 |\n| Fatigue | 25 + | | 43 | 30 | | 80 |\n| Rash | 18 | | 43 | 10 | 20* | 40 |\n| Nausea | | | + 62 | 10 | 10 | 60 |\n| Vomiting | | | 25 | | | 30 |\n| Anorexia | 6 | | 25 + | 10 | | 40 |\n| Dysgeusia | | | 18 | | | 50 |\n\n\n\n\n\nCitation Format: + Ingrid A. Mayer, Vandana Abramson, Justin Balko, Melinda Sanders, Dejan Juric, + David Solit, Yisheng Li, Lewis Cantley, Eric Winer, Carlos Arteaga. SU2C Phase + Ib study of the PI3K-alpha inhibitor BYL719 (alpelisib) with letrozole in + ER+/HER2-metastatic breast cancer. [abstract]. In: Proceedings of the 106th + Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; + Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract + nr CT232. doi:10.1158/1538-7445.AM2015-CT232\n\n [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01791478&atom=%2Fcanres%2F75%2F15_Supplement%2FCT232.atom", + "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2015-08-01", "journal": {"volume": "75", "name": "Cancer Research"}, "authors": + [{"authorId": "2346140", "name": "I. Mayer"}, {"authorId": "2186029", "name": + "V. Abramson"}, {"authorId": "66935619", "name": "J. Balko"}, {"authorId": + "46945931", "name": "M. Sanders"}, {"authorId": "3342243", "name": "D. Juric"}, + {"authorId": "2344124", "name": "D. Solit"}, {"authorId": "2111151410", "name": + "Yisheng Li"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2369378", "name": "E. Winer"}, {"authorId": "2057460", "name": "C. Arteaga"}]}, + {"paperId": "8ab27172e2befd2e4e919ae437f12a6fee332917", "externalIds": {"MAG": + "2172829973", "DOI": "10.1016/j.molcel.2015.10.018", "CorpusId": 35297754, + "PubMed": "26590711"}, "corpusId": 35297754, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/8ab27172e2befd2e4e919ae437f12a6fee332917", + "title": "Cancer''s Fuel Choice: New Flavors for a Picky Eater.", "abstract": + null, "venue": "Molecules and Cells", "year": 2015, "referenceCount": 78, + "citationCount": 107, "influentialCitationCount": 4, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1097276515008096/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2015-11-19", "journal": + {"volume": "60 4", "pages": "\n 514-23\n ", "name": "Molecular + cell"}, "authors": [{"authorId": "4772111", "name": "G. DeNicola"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "8c7b0dc80b44289baf4ffcc7804ea26c5766b03c", + "externalIds": {"MAG": "891517527", "DOI": "10.1158/1538-7445.PANCA2014-B45", + "CorpusId": 11408042}, "corpusId": 11408042, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/8c7b0dc80b44289baf4ffcc7804ea26c5766b03c", + "title": "Abstract B45: Pancreatic cancers depend on a non-canonical glutamine + metabolism pathway", "abstract": "Cancer cells exhibit metabolic dependencies + that distinguish them from their normal counterparts. Among these addictions + is an increased utilization of the amino acid glutamine (Gln) to fuel anabolic + processes. Recently, we reported the identification of a non-canonical pathway + of Gln utilization in human pancreatic cancer cells that is required for tumor + growth. While most cells utilize glutamate dehydrogenase (GLUD1) to convert + Gln-derived glutamate (Glu) into alpha-ketoglutarate (alpha-KG) in the mitochondria + to fuel the tricarboxylic acid cycle, pancreatic cancer cells rely on a distinct + pathway that integrates the mitochondrial and cytosolic aspartate aminotransferases + GOT2 and GOT1. By generating alpha-KG from Glu (in conjunction with the conversion + of oxaloacetate into aspartate), GOT2 fuels anaplerosis in place of GLUD1. + The Asp created is released into the cytosol and acted on by GOT1. This is + subsequently used through a series of reactions to yield cytosolic NADPH from + malic enzyme. Importantly, we have demonstrated that pancreatic cancers are + strongly dependent on this series of reactions to maintain redox homeostasis + which enables proliferation. Herein, we detail the subcellular compartmentalization + and consequences of the aforementioned reactions on pancreatic cancer metabolism. + We have also investigated the essentiality of this pathway in other contexts + and find that pancreatic cancers have a uniform and unique reliance on this + pathway, which may provide novel therapeutic approaches to treat these refractory + tumors. Citation Format: Costas A. Lyssiotis, Jaekyoung Son, Joesph D. Mancias, + Haoqiang Ying, Lewis C. Cantley, Alec C. Kimmelman. Pancreatic cancers depend + on a non-canonical glutamine metabolism pathway. [abstract]. In: Proceedings + of the AACR Special Conference on Pancreatic Cancer: Innovations in Research + and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; + Cancer Res 2015;75(13 Suppl):Abstract nr B45.", "venue": "", "year": 2015, + "referenceCount": 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2015-07-01", + "journal": {"volume": "75", "name": "Cancer Research"}, "authors": [{"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "38313825", "name": "J. Son"}, + {"authorId": "5810602", "name": "J. Mancias"}, {"authorId": "33312849", "name": + "H. Ying"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4668673", + "name": "A. Kimmelman"}]}, {"paperId": "8ca98de4025ffd44d835e52b0be3f097627d8d16", + "externalIds": {"CorpusId": 244114332}, "corpusId": 244114332, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/8ca98de4025ffd44d835e52b0be3f097627d8d16", + "title": "-Dependent Activation of the mTORC2 Kinase Complex", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 54, "citationCount": 3, + "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + null, "authors": [{"authorId": "3420906", "name": "Pengda Liu"}, {"authorId": + "40383426", "name": "Wenjian Gan"}, {"authorId": "50611901", "name": "Y. R. + Chin"}, {"authorId": "9924372", "name": "K. Ogura"}, {"authorId": "51049890", + "name": "Jian-ping Guo"}, {"authorId": "2016457046", "name": "Jinfang Zhang"}, + {"authorId": "2152593405", "name": "Bin Wang"}, {"authorId": "4037343", "name": + "J. Blenis"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "145751285", "name": "A. Toker"}, {"authorId": "2072391827", "name": "Bing + Su"}, {"authorId": "144084152", "name": "Wenyi Wei"}]}, {"paperId": "9ded8e1b19e7cb6c4a3a643e3bb8cb75d24f9cf0", + "externalIds": {"MAG": "1570826410", "DOI": "10.1158/1538-7445.PANCA2014-PR13", + "CorpusId": 217974924}, "corpusId": 217974924, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/9ded8e1b19e7cb6c4a3a643e3bb8cb75d24f9cf0", + "title": "Abstract PR13: Pancreatic tumor stem cells resistant to inhibition + of oncogenic signaling are dependent on mitochondrial function", "abstract": + "Pancreatic ductal adenocarcinoma (PDAC) continues to have a poor prognosis + despite extensive characterization of underlying genetic lesions. Although + KRAS mutation is a signature driver event required for tumor development and + maintenance, all the attempts made to target oncogene-driven signaling pathways + have been met with minimal impact on survival and tumors eventually relapse, + suggesting that ablation of oncogenic pathways fails to eradicate tumor cells. + We used a genetically engineered mouse model of PDAC in which we could control + the expression of mutant KRAS in a time- and tissue-specific manner to study + the effects of ablating oncogenic signaling on PDAC cells. As previously described + (Ying et al. 2012), this model showed rapid tumor growth when KRAS was expressed, + followed by robust tumor regression upon oncogene ablation. However a small + population of tumor cells survive genetic and pharmacological inactivation + of KRAS. These surviving cells are tumor stem cells able to remain in a quiescent + state for months before repopulating the original tumor upon reactivation + of KRAS signaling. In depth transcriptomic and metabolomic analyses revealed + surviving cells have different metabolic features with respect to the bulk + of tumor cells, showing a prominent expression of genes governing mitochondrial + function, \u03b2-oxidation and autophagy, as well as strong reliance on mitochondrial + respiration, yet these cells also displayed impaired glycolytic capacity. + In accord with their decreased dependence on glycolysis for cellular energetics + and their complete absence of glycolytic reserve, these PDAC surviving tumor + stem cells show high sensitivity to oxidative phosphorylation inhibitors, + which prevented tumor recurrence. Our integrated analysis paves the way for + new therapeutic strategies combining KRAS signaling and oxidative phosphorylation + inhibition to completely eradicate pancreatic ductal adenocarcinoma. This + abstract is also presented as Poster A87. Citation Format: Andrea Viale, Piergiorgio + Pettazzoni, Costas Lyssiotis, Haoqiang Ying, Nora Sanchez, Matteo Marchesini, + Alessandro Carugo, Tessa Green, Sahil Seth, Virginia Giuliani, Timothy Heffernan, + Alec Kimmelman, Huamin Wang, Jason Fleming, Lewis Cantley, Ronald DePinho, + Giulio Draetta. Pancreatic tumor stem cells resistant to inhibition of oncogenic + signaling are dependent on mitochondrial function. [abstract]. In: Proceedings + of the AACR Special Conference on Pancreatic Cancer: Innovations in Research + and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; + Cancer Res 2015;75(13 Suppl):Abstract nr PR13.", "venue": "", "year": 2015, + "referenceCount": 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2015-07-01", + "journal": {"volume": "75", "name": "Cancer Research"}, "authors": [{"authorId": + "49837367", "name": "A. Viale"}, {"authorId": "47110079", "name": "P. Pettazzoni"}, + {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "33312849", + "name": "H. Ying"}, {"authorId": "3461293", "name": "Nora S. Sanchez"}, {"authorId": + "48455352", "name": "M. Marchesini"}, {"authorId": "8457336", "name": "A. + Carugo"}, {"authorId": "39319755", "name": "T. Green"}, {"authorId": "4288735", + "name": "S. Seth"}, {"authorId": "8048176", "name": "V. Giuliani"}, {"authorId": + "3095168", "name": "T. Heffernan"}, {"authorId": "4668673", "name": "A. Kimmelman"}, + {"authorId": "2109007858", "name": "Huamin Wang"}, {"authorId": "144926646", + "name": "J. Fleming"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5593407", "name": "R. DePinho"}, {"authorId": "5336286", "name": "G. Draetta"}]}, + {"paperId": "9f73e4f72ac1fe913ba591cba8ded2b5285d9ab0", "externalIds": {"MAG": + "2565332264", "DOI": "10.1158/1538-7445.AM2015-4714", "CorpusId": 79133222}, + "corpusId": 79133222, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9f73e4f72ac1fe913ba591cba8ded2b5285d9ab0", + "title": "Abstract 4714: Targeting p53 mutant cancers through inhibition of + the phosphatidylinositol-5-phosphate 4-kinases", "abstract": "The bulk of + cellular phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) is generated by + the canonical pathway in which a 5-kinase converts phosphatidylinositol-4-phosphate + (PI-4-P) to PI-4,5-P2. However, several years ago we discovered that PI-4, + 5-P2 can also be generated at intracellular sites by a family of kinases that + phosphorylate the 4 position of phosphatidylinositol-5-phosphate (PI-5-P), + a lipid that was not previously known to exist in nature. These enzymes are + called the type 2 phosphatidylinositol-5-phosphate 4-kinases (PI5P4Ks). To + date, we have shown that a subset of breast cancers express high levels of + PI5P4K\u03b1 and/or \u03b2, and have provided evidence that these kinases + are essential for growth in the absence of p53 (Emerling et al., 2013). Furthermore, + we showed that PI5P4K\u03b1 and \u03b2 play critical roles in mediating changes + in metabolism in response to cellular stress, in particular, stress that occurs + in the absence of p53. Here, we disclose the discovery of potent and selective + inhibitors of PI5P4K (Kis in the range of 10 to 200 nM). These novel PI5P4K + inhibitors have provided us with powerful tools to further investigate the + role of the PI5P4K enzymes in cancer metabolism. Through pharmacological inhibition + of PI5P4K, we now have support that PI5P4K provides an alternative pathway + to p53 in regard to mediating responses to metabolic and oxidative stress, + thereby suggesting that the PI5P4K enzymes are essential for survival mechanisms + when p53 function is lost. Above all, these inhibitors may be effective therapies + not only for breast cancers with genetic aberrations in TP53, but in all cancer + types with loss of p53 function. Supported by DOD Breast Research Program + Breakthrough Award to B.M.E. References Emerling BM, Hurov JB, Poulogiannis + G, Tsukazawa KS, Wulf G, Bell EL, Shim H, Choo-Wing R, Bellinger G, Lamia + KA, Rameh LE, Sasaki A, Asara JM, Yuan X, Bullock A, Brown V, Signoretti S, + and Cantley LC. (2013) Depletion of a Putatively Druggable Class of Phosphatidylinositol + Kinases Inhibits Growth of p53 Null Tumors. Cell. Nov 7; 155 (4): 844-57. + Citation Format: Brooke M. Emerling, Zhiwei Yang, Ryan Loughran, T.Jonathan + Yang, Jared Johnson, Rajan Pragani, Mindy Davis, Min Shen, Matthew Boxer, + Anton Simeonov, Lewis C. Cantley. Targeting p53 mutant cancers through inhibition + of the phosphatidylinositol-5-phosphate 4-kinases. [abstract]. In: Proceedings + of the 106th Annual Meeting of the American Association for Cancer Research; + 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 + Suppl):Abstract nr 4714. doi:10.1158/1538-7445.AM2015-4714", "venue": "", + "year": 2015, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2015-08-01", "journal": {"volume": "75", "pages": "4714-4714", "name": "Cancer + Research"}, "authors": [{"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "50109290", "name": "Zhiwei Yang"}, {"authorId": "31875049", "name": "Ryan + Loughran"}, {"authorId": "2115865796", "name": "T. Yang"}, {"authorId": "145916288", + "name": "Jared L. Johnson"}, {"authorId": "5123505", "name": "R. Pragani"}, + {"authorId": "29195749", "name": "Mindy I. Davis"}, {"authorId": "145829790", + "name": "M. Shen"}, {"authorId": "3275486", "name": "M. Boxer"}, {"authorId": + "145183304", "name": "A. Simeonov"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "a0aab62dfd82bd8add29bd9f42341c4dcdd0f92e", "externalIds": {"MAG": + "1930038475", "DOI": "10.1158/2159-8290.CD-15-0460", "CorpusId": 9682393, + "PubMed": "26293922"}, "corpusId": 9682393, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/a0aab62dfd82bd8add29bd9f42341c4dcdd0f92e", + "title": "PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex.", + "abstract": "UNLABELLED\nmTOR serves as a central regulator of cell growth + and metabolism by forming two distinct complexes, mTORC1 and mTORC2. Although + mechanisms of mTORC1 activation by growth factors and amino acids have been + extensively studied, the upstream regulatory mechanisms leading to mTORC2 + activation remain largely elusive. Here, we report that the pleckstrin homology + (PH) domain of SIN1, an essential and unique component of mTORC2, interacts + with the mTOR kinase domain to suppress mTOR activity. More importantly, PtdIns(3,4,5)P3, + but not other PtdInsPn species, interacts with SIN1-PH to release its inhibition + on the mTOR kinase domain, thereby triggering mTORC2 activation. Mutating + critical SIN1 residues that mediate PtdIns(3,4,5)P3 interaction inactivates + mTORC2, whereas mTORC2 activity is pathologically increased by patient-derived + mutations in the SIN1-PH domain, promoting cell growth and tumor formation. + Together, our study unravels a PI3K-dependent mechanism for mTORC2 activation, + allowing mTORC2 to activate AKT in a manner that is regulated temporally and + spatially by PtdIns(3,4,5)P3.\n\n\nSIGNIFICANCE\nThe SIN1-PH domain interacts + with the mTOR kinase domain to suppress mTOR activity, and PtdIns(3,4,5)P3 + binds the SIN1-PH domain to release its inhibition on the mTOR kinase domain, + leading to mTORC2 activation. Cancer patient-derived SIN1-PH domain mutations + gain oncogenicity by loss of suppressing mTOR activity as a means to facilitate + tumorigenesis.", "venue": "Cancer Discovery", "year": 2015, "referenceCount": + 55, "citationCount": 265, "influentialCitationCount": 17, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4631654?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2015-11-01", "journal": {"volume": + "5 11", "pages": "\n 1194-209\n ", "name": "Cancer discovery"}, + "authors": [{"authorId": "3420906", "name": "Pengda Liu"}, {"authorId": "40383426", + "name": "Wenjian Gan"}, {"authorId": "50611901", "name": "Y. R. Chin"}, {"authorId": + "9924372", "name": "K. Ogura"}, {"authorId": "51049890", "name": "Jian-ping + Guo"}, {"authorId": "2016457046", "name": "Jinfang Zhang"}, {"authorId": "2152593405", + "name": "Bin Wang"}, {"authorId": "4037343", "name": "J. Blenis"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "145751285", "name": "A. Toker"}, + {"authorId": "2054512630", "name": "Bing Su"}, {"authorId": "144084152", "name": + "Wenyi Wei"}]}, {"paperId": "a4c080fce099ef7b79d45f81d3f94c6937a5acd1", "externalIds": + {"MAG": "1524553021", "DOI": "10.1158/1538-7445.MEL2014-B09", "CorpusId": + 71090082}, "corpusId": 71090082, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/a4c080fce099ef7b79d45f81d3f94c6937a5acd1", + "title": "Abstract B09: Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 + association and cell proliferation", "abstract": "BRAF is an oncogenic protein + kinase that drives cell growth and proliferation through the MEK-ERK signaling + pathway. BRAF inhibitors have demonstrated antitumor efficacy in melanoma + therapy but have also been found to be associated with the development of + cutaneous squamous cell carcinomas (cSCCs) in certain patients. Here, we report + that BRAF is phosphorylated at Ser729 by AMP-activated protein kinase (AMPK), + a critical energy sensor. This phosphorylation promotes the association of + BRAF with 14-3-3 proteins and disrupts its interaction with the KSR1 scaffolding + protein, leading to attenuation of the MEK-ERK signaling. We also show that + phosphorylation of BRAF by AMPK impairs keratinocyte cell proliferation and + cell-cycle progression. Furthermore, AMPK activation attenuates BRAF inhibitor-induced + ERK hyperactivation in keratinocytes and epidermal hyperplasia in mouse skin. + Our findings reveal a mechanism for regulating BRAF signaling in response + to energy stress and suggest a strategy for preventing the development of + cSCCs associated with BRAF-targeted therapy. Citation Format: Che-Hung Shen, + Ping Yuan, Rolando Perez-Lorenzo, Yaqing Zhang, Sze Xian Lee, Yang Ou, Li + Cai, John M. Asara, Lewis C. Cantley, Bin Zheng. Phosphorylation of BRAF by + AMPK impairs BRAF-KSR1 association and cell proliferation. [abstract]. In: + Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology + to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer + Res 2015;75(14 Suppl):Abstract nr B09.", "venue": "", "year": 2015, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-07-15", "journal": {"volume": + "75", "name": "Cancer Research"}, "authors": [{"authorId": "83946576", "name": + "Che-Hung Shen"}, {"authorId": "22261570", "name": "P. Yuan"}, {"authorId": + "1398525526", "name": "R. P\u00e9rez-Lorenzo"}, {"authorId": "1591129979", + "name": "Yaqing Zhang"}, {"authorId": "2108098779", "name": "S. Lee"}, {"authorId": + "2057924812", "name": "Yang Ou"}, {"authorId": "2112831690", "name": "Li Cai"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "143918840", "name": "B. Zheng"}]}, {"paperId": + "a68bbd0f336c26d04681e948bf2cf98850e15060", "externalIds": {"DOI": "10.1016/j.cell.2015.01.021", + "CorpusId": 14340176}, "corpusId": 14340176, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/a68bbd0f336c26d04681e948bf2cf98850e15060", + "title": "Acetate Fuels the Cancer Engine", "abstract": null, "venue": "Cell", + "year": 2015, "referenceCount": 6, "citationCount": 35, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867415000641/pdf", + "status": null}, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": {"volume": "160", "name": "Cell"}, "authors": [{"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "a88118e09f8d4a25ef2fce5ec88bce255a9a6cff", "externalIds": {"MAG": + "2305691503", "DOI": "10.1158/1538-8514.PI3K14-IA01", "CorpusId": 86884832}, + "corpusId": 86884832, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/a88118e09f8d4a25ef2fce5ec88bce255a9a6cff", + "title": "Abstract IA01: Targeting phosphoinositide 3-kinase for cancer therapy", + "abstract": "Phosphoinositide 3-kinase (PI3K) is a central enzyme in a signaling + pathway that mediates cellular responses to insulin and other growth factors. + The signaling pathway involving insulin, PI3K and the downstream components + of AKT and mTOR is highly conserved from worms and flies to humans and genetic + analysis of the pathway has revealed a conserved role in regulating glucose + metabolism and cell growth. Germline mutational events that lead to hyperactivation + of the PI3K pathway result in hamartoma syndromes and cancers. Sporadic activating + mutations in PIK3CA, encoding the p110alpha catalytic subunit of PI3K or inactivating + mutations in PTEN, a phosphoinositide 3-phosphatases that reverses the effects + of PI3K, are among the most common events in solid tumors. More than thirty + drugs that target PI3K and other components of this pathway are in clinical + trials for a variety of cancers. It is likely that PI3K pathway inhibitors + will need to be combined with other drugs to be broadly effective. We have + employed genetically engineered mouse models that develop cancers due to mutations + in genes in the PI3K pathway and are using these models to explore the efficacy + of PI3K pathway inhibitors as single agents or in combination with other drugs. + The role of PI3K inhibitors for treating cancers in these mouse models and + in human trials will be discussed. Citation Format: Lewis C. Cantley. Targeting + phosphoinositide 3-kinase for cancer therapy. [abstract]. In: Proceedings + of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; + Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther + 2015;14(7 Suppl):Abstract nr IA01.", "venue": "", "year": 2015, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-07-01", "journal": {"volume": + "14", "name": "Molecular Cancer Therapeutics"}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "a89ec81ac3297925fbb420c55d2a86c6c9a0dc00", + "externalIds": {"MAG": "2563659124", "DOI": "10.1158/1538-7445.AM2015-1081", + "CorpusId": 78196675}, "corpusId": 78196675, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/a89ec81ac3297925fbb420c55d2a86c6c9a0dc00", + "title": "Abstract 1081: Non-random genomic alterations in BRCA1-related breast + cancer", "abstract": "BRCA1-related breast cancer is characterized by a high + degree of genomic instability. However, to which extent this instability is + a random result of the homologous recombination defect or the selection of + the tumor phenotype, is unknown. The objective of this study is to investigate + the genomic aberrations (copy number variation and somatic mutations) of BRCA1-related + breast cancer, using a mouse model, to identify likely nonrandom aberrations + and their biological functions. We examined genomic aberrations of three independent + BRCA1-related tumors from a genetically engineered mouse model, K14-Cre BRCA1f/fp53f/f. + Tumors had been propagated in Cre-negative littermates and liver tissue of + the recipient mice from the controls were used as a germline control. Fresh + frozen tumors and normal samples were used for exome sequencing and RNA-seq + using Illumina technology. A commonly used workflow, GATK, was used for the + sequence alignment, preprocessing and calling somatic mutations. VarScan2 + was used for calling somatic copy number variations. We investigate the prevalence + of common aberrations among these mouse in human BRCA1-related breast and + ovarian cancer from The Cancer Genome Atlas (TCGA). We used the BioMart software + tool to map mouse genes to human genes for the cross species analysis. After + identifying common aberrant regions and genes across human and mouse we applied + enrichment analysis using GOSeq, MetaCore and MSigDB software tools to identify + the biological functions of the genetic alterations observed in BRCA1-related + breast cancer across species. The analysis of exome sequencing data from BRCA1-related + mouse tumors revealed surprisingly similar patterns of CNVs and rates of non-synonymous + mutations. Correspondingly, distinct pattern were identified with regard to + CNVs in human BRCA1-related breast and ovarian cancer. The cross species analysis + of BRCA1-related TCGA ovarian and breast cancer tumors and BRCA1-related mouse + tumors identified commonly aberrant regions that mapped to the long arms of + human chromosomes 1, 8, 17 and 20 in both breast and ovarian cancer. Functionally, + the blocks of genes that were commonly amplified in BRCA1-related breast or + ovarian cancer included genes that transduce mitogenic signaling and ligand + independent activation of estrogen receptors ESR1 and ESR2 as well as genes + of the renin-angiotensin system. To conclude, copy number aberrations in BRCA1-related + breast or ovarian cancers are not random and enrich for genes that enforce + mitogenic signaling. The data support the notion that in addition to loss + of cell cycle checkpoint control, tumor development requires activation of + a mitogenic signaling program that could potentially be targeted for treatment. + Citation Format: Sheida Nabavi, Kristina M. Holton, Ashish Juvekar, Nicholas + Wang, Olivier Elemento, Lewis C. Cantley, Gerburg M. Wulf. Non-random genomic + alterations in BRCA1-related breast cancer. [abstract]. In: Proceedings of + the 106th Annual Meeting of the American Association for Cancer Research; + 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 + Suppl):Abstract nr 1081. doi:10.1158/1538-7445.AM2015-1081", "venue": "", + "year": 2015, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2015-08-01", "journal": {"volume": "75", "pages": "1081-1081", "name": "Cancer + Research"}, "authors": [{"authorId": "145834073", "name": "S. Nabavi"}, {"authorId": + "6803235", "name": "K. Holton"}, {"authorId": "49149990", "name": "Ashish + Juvekar"}, {"authorId": "1722194", "name": "Nicholas J. Wang"}, {"authorId": + "150097652", "name": "O. Elemento"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "31554501", "name": "G. Wulf"}]}, {"paperId": "c5962ef8f08c5b974306298f6f1ca0be2e095ff3", + "externalIds": {"MAG": "2492086421", "DOI": "10.1002/9781118468678.CH32", + "CorpusId": 89396393}, "corpusId": 89396393, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/c5962ef8f08c5b974306298f6f1ca0be2e095ff3", + "title": "The Phosphatidylinositol 3\u2010Kinase Pathway in Human Malignancies", + "abstract": null, "venue": "", "year": 2015, "referenceCount": 75, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-10-30", "journal": {"volume": + "", "pages": "315-324", "name": ""}, "authors": [{"authorId": "4677205", "name": + "S. Klempner"}, {"authorId": "122695603", "name": "Thanh-Trang T. Vo"}, {"authorId": + "6324437", "name": "A. Myers"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "ceeee343b160fbdb557978c6ee3e460ebc1421fe", "externalIds": {"PubMedCentral": + "4601138", "MAG": "2114439592", "DOI": "10.1186/s40170-015-0137-1", "CorpusId": + 1204277, "PubMed": "26462257"}, "corpusId": 1204277, "publicationVenue": {"id": + "787ea3c5-4d66-450c-b13d-9f7934429b7f", "name": "Cancer & Metabolism", "type": + "journal", "alternate_names": ["Cancer Metab", "Cancer and Metabolism", "Cancer Metab"], + "issn": "2049-3002", "url": "http://www.cancerandmetabolism.com/"}, "url": + "https://www.semanticscholar.org/paper/ceeee343b160fbdb557978c6ee3e460ebc1421fe", + "title": "Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven + metabolic catastrophe induced by \u00df-lapachone", "abstract": null, "venue": + "Cancer & Metabolism", "year": 2015, "referenceCount": 46, "citationCount": + 97, "influentialCitationCount": 4, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2015-10-12", "journal": {"volume": "3", "name": "Cancer + & Metabolism"}, "authors": [{"authorId": "35784792", "name": "G. Chakrabarti"}, + {"authorId": "145442892", "name": "Z. Moore"}, {"authorId": "5617652", "name": + "Xiuquan Luo"}, {"authorId": "4735589", "name": "Mariya Ilcheva"}, {"authorId": + "13336581", "name": "Aktar Ali"}, {"authorId": "47393233", "name": "Mahesh + S. Padanad"}, {"authorId": "2118116344", "name": "Yunyun Zhou"}, {"authorId": + "145668114", "name": "Yang Xie"}, {"authorId": "4579757", "name": "S. Burma"}, + {"authorId": "3619786", "name": "P. Scaglioni"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "5834413", "name": "R. Deberardinis"}, {"authorId": + "4668673", "name": "A. Kimmelman"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "6434802", "name": "D. Boothman"}]}, {"paperId": "db252b726957e883502f52fb5b2ada5b743e09d8", + "externalIds": {"MAG": "2262820072", "DOI": "10.1158/1538-8514.PI3K14-A33", + "CorpusId": 87639270}, "corpusId": 87639270, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/db252b726957e883502f52fb5b2ada5b743e09d8", + "title": "Abstract A33: Utilizing insulin the treatment of prostate cancer + with BKM120 abrogates the therapeutic effect of PI3K pathway inhibition", + "abstract": "Genetic aberrations in PTEN, the negative regulator of phosphoinositide + 3-kinase (PI3K) signaling, are common in prostate cancers (PCA) with high + Gleason Scores and correlate with adverse outcome. Currently, PI3K inhibitors, + as single agents and in combination, have entered Phase I and II clinical + trials for metastatic castrate resistant PCA. Alpha-specific and pan-PI3K + inhibitors cause hyperglycemia as an on-target side effect by blocking insulin-dependent + PI3K signaling in the liver and muscle and patients develop hyperinsulinemia + in response to hyperglycemia, and insulin treatment is often needed to manage + drug-induced hyperglycemia. Using human and murine prostate cancer cell lines, + we examined the effect of adding insulin to BKM120 treatment on PI3K pathway + activation. Using human prostate cancer cell lines LNCaP and PC3 which both + express insulin receptor (IR) and IGF-1 receptor (IGF-1R), we found downregulation + of the PI3K pathway by BKM120 treatment and upregulation of the PI3K pathway + by insulin treatment, as assessed by AKT phosphorylation. In both cell lines, + the PI3K pathway is reactivated when insulin is added to BKM120 treatment. + Using cells derived from PTEN-/-P53-/- murine PCA which express low levels + of IR and IGF-1R, we found minimal activation of the PI3K pathway with insulin, + either alone or in combination with BKM120. Conversely, using cells derived + from Myc-overexpressing mice which express high levels of IR and IGF-1R, we + found robust activation of the PI3K pathway with insulin treatment. More importantly, + while BKM120 abolished PI3K activity in the Myc-overexpressing cells, the + addition of insulin to BKM120 resulted in the reactivation of the PI3K pathway + to the level of PI3K pathway activity without BKM120 treatment. Together these + findings suggest that the use of insulin in combination with BKM120 abrogates + the therapeutic effect of PI3K inhibition. In addition, they indicate that + PCAs that have high levels of IR and/or IGF-1 expression are particularly + sensitive to PI3K inhibitors as well as insulin reactivation of the PI3K pathway. + Citation Format: Lily C. Wang, Sunnie S. Kim, David M. Nanus, Lewis C. Cantley. + Utilizing insulin the treatment of prostate cancer with BKM120 abrogates the + therapeutic effect of PI3K pathway inhibition. [abstract]. In: Proceedings + of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; + Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther + 2015;14(7 Suppl):Abstract nr A33.", "venue": "", "year": 2015, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2015-07-01", "journal": {"volume": "14", "name": "Molecular + Cancer Therapeutics"}, "authors": [{"authorId": "2117931332", "name": "Lily + C. Wang"}, {"authorId": "2109648661", "name": "Sunnie S. Kim"}, {"authorId": + "5430838", "name": "D. Nanus"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "dc88d4dde91802c193fb9f9b39ce757150348bfc", "externalIds": {"MAG": + "1634157550", "DOI": "10.1016/j.cellsig.2015.09.004", "CorpusId": 31757640, + "PubMed": "26363466"}, "corpusId": 31757640, "publicationVenue": {"id": "9b987329-d573-412b-a782-84a181c184b9", + "name": "Cellular Signalling", "type": "journal", "alternate_names": ["Cell + Signal"], "issn": "0898-6568", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/525462/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/08986568"]}, + "url": "https://www.semanticscholar.org/paper/dc88d4dde91802c193fb9f9b39ce757150348bfc", + "title": "Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling + regulates cartilage development by modulating chondrocyte hypertrophy.", "abstract": + null, "venue": "Cellular Signalling", "year": 2015, "referenceCount": 71, + "citationCount": 8, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc4847727?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2015-12-01", "journal": {"volume": "27 12", "pages": "\n 2389-400\n ", + "name": "Cellular signalling"}, "authors": [{"authorId": "2144149588", "name": + "Jeong-Ah Kim"}, {"authorId": "12348977", "name": "Suhjean Im"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2115948992", "name": "Dae-Won + Kim"}]}, {"paperId": "e4482bc435864ecc7c5aff92a1b5561a369157cb", "externalIds": + {"MAG": "2978089074", "DOI": "10.2210/pdb3x05/pdb", "CorpusId": 210513033}, + "corpusId": 210513033, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e4482bc435864ecc7c5aff92a1b5561a369157cb", + "title": "Crystal structure of PIP4KIIBETA T201M complex with AMP", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2015-10-14", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2775065", "name": "K. Takeuchi"}, + {"authorId": "121709354", "name": "Y. Lo"}, {"authorId": "49715313", "name": + "K. Sumita"}, {"authorId": "5638813", "name": "M. Senda"}, {"authorId": "49515406", + "name": "Jumpei Terakawa"}, {"authorId": "1485705386", "name": "A. Dimitoris"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "152671464", + "name": "Mika Sasaki"}, {"authorId": "6824343", "name": "H. Yoshino"}, {"authorId": + "49891201", "name": "Y. Zhang"}, {"authorId": "4049626", "name": "E. Kahoud"}, + {"authorId": "91895026", "name": "T. Takano"}, {"authorId": "10207871", "name": + "T. Yokota"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1394348007", "name": "J. Asara"}, {"authorId": "47983250", "name": "T. Ishida"}, + {"authorId": "144714771", "name": "I. Shimada"}, {"authorId": "145457715", + "name": "T. Daikoku"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "50162552", "name": "T. Senda"}, {"authorId": "47742211", "name": "A. Sasaki"}]}, + {"paperId": "eae582038c8e26db2e68560dcfcdaf4a23ae71fd", "externalIds": {"MAG": + "2567383469", "DOI": "10.1158/1538-7445.AM2015-2650", "CorpusId": 78399704}, + "corpusId": 78399704, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/eae582038c8e26db2e68560dcfcdaf4a23ae71fd", + "title": "Abstract 2650: PI 3-Kinase inhibitors enhance the synthetic lethality + of Parp inhibitors", "abstract": "Introduction: Clinical trials have shown + promising responses of BRCA-linked breast and ovarian cancers to PARP inhibitor + therapy, but remissions are often short-lived and incomplete. Frequent loss + of INPP4B and PTEN leads to activation in the PI3K pathway in TNBC, making + the PI3K pathway an attractive treatment target. Here we present mechanistic + data that explain how PI3K- and PARP-inhibition enhance each other. Methods: + We examined the effects of PI3K-inhibitors BKM120 or BYL719 and PARP-inhibitor + Olaparib on the metabolism of HCC1937 cells (BRCA1 5382C mutation and homozygous + deletion of PTEN and p53) measuring lactic acid production, via seahorse analysis, + carbon metabolism using targeted Mass Spectrometry (LC-MS/MS) and DNA synthesis. + PI3K- but not Akt- or SGK-inhibition induced a DNA damage response in this + BRCA1 mutant cell line as well as in a mouse model of BRCA1-related breast + cancer (K14-Cre BRCA1f/f p53f/f) mouse model. Summary: Metabolic profiling + showed that PI3K-inhibition decreased flux through glycolysis and specifically + through the non-oxidative pentose-phosphate pathway, the main source of ribose-5-phosphate + required for the de novo synthesis of nucleotides in BRCA1-mutant breast cancer + cells. Nucleotide shortage led to replication stress with the appearance of + \u03b3H2AX, increased poly-ADP-ribosylation and an acute drop in DNA synthesis + in cell cultures as well as in vivo. PI3K inhibition led to a reduced and + error-prone S-phase due to a decrease in nucleotide biosynthesis which could + be rescued upon exogenous supply of nucleosides. In a mouse model (K14-Cre + BRCA1f/fp53f/f induced breast cancers) we could confirm that both BKM120 and + BYL719 enhanced the efficacy of Parp-inhibitor Olaparib (median PFS for Olaparib + 50 days, for BKM120 4 days, for BYL719 6 days and for both combinations, BKM120+Olaparib + and BYL719+Olaparib > 120 days). Conclusion: Preceding cell cycle arrest, + PI3K-inhibition leads to a decrease in DNA synthesis due to decreased Ribose-5-phosphate + production required for nucleotide synthesis. PI3K-inhibitors lower nucleotide + pools, lead to impaired DNA damage repair and S-phase progression and further + augment the synthetic lethality of Parp-inhibitors in BRCA1-related breast + cancer. Citation Format: Ashish P. Juvekar, Sina Yadegarynia, Hai Hu, Costas + A. Lyssiotis, Hui Liu, John M. Asara, Ralph Scully, Lewis C. Cantley, Gerburg + M. Wulf. PI 3-Kinase inhibitors enhance the synthetic lethality of Parp inhibitors. + [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association + for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): + AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2650. doi:10.1158/1538-7445.AM2015-2650", + "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2015-08-01", "journal": {"volume": "75", "pages": "2650-2650", "name": "Cancer + Research"}, "authors": [{"authorId": "49149990", "name": "Ashish Juvekar"}, + {"authorId": "3893473", "name": "S. Yadegarynia"}, {"authorId": "113164867", + "name": "Hai Hu"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "2146671919", "name": "Hui Liu"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "143905392", "name": "R. Scully"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "31554501", "name": "G. Wulf"}]}, {"paperId": + "f3f92601ad4094848415f83af0970902347c6aef", "externalIds": {"MAG": "2079742730", + "DOI": "10.1016/J.JURO.2015.02.1573", "CorpusId": 72428359}, "corpusId": 72428359, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/f3f92601ad4094848415f83af0970902347c6aef", + "title": "MP46-10 UTILIZING INSULIN IN THE TREATMENT OF PROSTATE CANCER WITH + BKM120 ABROGATES THE THERAPEUTIC EFFECT OF PI3K PATHWAY INHIBITION", "abstract": + null, "venue": "", "year": 2015, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2015-04-01", "journal": {"volume": "193", "name": + "The Journal of Urology"}, "authors": [{"authorId": "2117931332", "name": + "Lily C. Wang"}, {"authorId": "5430838", "name": "D. Nanus"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "f748f716d661e711f508ad20f7408c6a6b69fcc1", + "externalIds": {"MAG": "918031449", "DOI": "10.1016/j.bbadis.2015.07.009", + "CorpusId": 23529456, "PubMed": "26170063"}, "corpusId": 23529456, "publicationVenue": + {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", "name": "Biochimica et Biophysica + Acta", "type": "journal", "alternate_names": ["Biochim Biophys Acta"], "issn": + "0006-3002", "alternate_issns": ["1878-2434"], "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/f748f716d661e711f508ad20f7408c6a6b69fcc1", + "title": "Adaptive changes in amino acid metabolism permit normal longevity + in mice consuming a low-carbohydrate ketogenic diet.", "abstract": null, "venue": + "Biochimica et Biophysica Acta", "year": 2015, "referenceCount": 50, "citationCount": + 69, "influentialCitationCount": 4, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2015-10-01", "journal": {"volume": "1852 10 Pt A", "pages": "\n 2056-65\n ", + "name": "Biochimica et biophysica acta"}, "authors": [{"authorId": "4157845", + "name": "N. Douris"}, {"authorId": "1853856", "name": "T. Melman"}, {"authorId": + "14412308", "name": "Jordan M Pecherer"}, {"authorId": "6720534", "name": + "P. Pissios"}, {"authorId": "3896998", "name": "J. Flier"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "1398311201", "name": "E. Maratos-Flier"}]}, {"paperId": "fcdb08e1917bbdf40cdb4f290f03bfa5a8ad4f68", + "externalIds": {"MAG": "20514746", "DOI": "10.1007/978-1-4939-2425-7_4", "CorpusId": + 37697371, "PubMed": "25859943"}, "corpusId": 37697371, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/fcdb08e1917bbdf40cdb4f290f03bfa5a8ad4f68", + "title": "Computational prediction of protein-protein interactions.", "abstract": + null, "venue": "Methods in molecular biology", "year": 2015, "referenceCount": + 49, "citationCount": 23, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4435844?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Computer Science"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Computer Science", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle", "Review"], "publicationDate": null, + "journal": {"volume": "1278", "pages": "\n 57-75\n ", "name": + "Methods in molecular biology"}, "authors": [{"authorId": "2402804", "name": + "T. Ehrenberger"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "88402408", "name": "M. Yaffe"}]}, {"paperId": "015888ad63bbcc3e642726f98737ff68f027b0fb", + "externalIds": {"MAG": "2147683295", "DOI": "10.1101/cshperspect.a022913", + "CorpusId": 27016870, "PubMed": "25359498"}, "corpusId": 27016870, "publicationVenue": + {"id": "9022e356-13cd-4b20-b9c8-b71402126832", "name": "Cold Spring Harbor + Perspectives in Biology", "type": "journal", "alternate_names": ["Cold Spring + Harb Perspect Biology"], "issn": "1943-0264", "url": "https://cshperspectives.cshlp.org/", + "alternate_urls": ["http://cshperspectives.org/"]}, "url": "https://www.semanticscholar.org/paper/015888ad63bbcc3e642726f98737ff68f027b0fb", + "title": "Signal transduction: From the atomic age to the post-genomic era.", + "abstract": "We have come a long way in the 55 years since Edmond Fischer + and the late Edwin Krebs discovered that the activity of glycogen phosphorylase + is regulated by reversible protein phosphorylation. Many of the fundamental + molecular mechanisms that operate in biological signaling have since been + characterized and the vast web of interconnected pathways that make up the + cellular signaling network has been mapped in considerable detail. Nonetheless, + it is important to consider how fast this field is still moving and the issues + at the current boundaries of our understanding. One must also appreciate what + experimental strategies have allowed us to attain our present level of knowledge. + We summarize here some key issues (both conceptual and methodological), raise + unresolved questions, discuss potential pitfalls, and highlight areas in which + our understanding is still rudimentary. We hope these wide-ranging ruminations + will be useful to investigators who carry studies of signal transduction forward + during the rest of the 21st century.", "venue": "Cold Spring Harbor Perspectives + in Biology", "year": 2014, "referenceCount": 295, "citationCount": 22, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://cshperspectives.cshlp.org/content/6/12/a022913.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2014-12-01", "journal": + {"volume": "6 12", "pages": "\n a022913\n ", "name": "Cold + Spring Harbor perspectives in biology"}, "authors": [{"authorId": "145842074", + "name": "J. Thorner"}, {"authorId": "143683912", "name": "T. Hunter"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3816999", "name": "Richard + Sever"}]}, {"paperId": "022e4c787744c47a0172d4ebf198196b88bbddcb", "externalIds": + {"MAG": "2148931486", "DOI": "10.1038/nature13079", "CorpusId": 4446551, "PubMed": + "24670654"}, "corpusId": 4446551, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/022e4c787744c47a0172d4ebf198196b88bbddcb", + "title": "Cell-cycle-regulated activation of Akt kinase by phosphorylation + at its carboxyl terminus", "abstract": null, "venue": "Nature", "year": 2014, + "referenceCount": 48, "citationCount": 299, "influentialCitationCount": 15, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4076493?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2014-04-24", "journal": {"volume": "508", "pages": "541-545", + "name": "Nature"}, "authors": [{"authorId": "3420906", "name": "Pengda Liu"}, + {"authorId": "69874482", "name": "M. Begley"}, {"authorId": "5528225", "name": + "W. Michowski"}, {"authorId": "4403700", "name": "H. Inuzuka"}, {"authorId": + "38246030", "name": "M. Ginzberg"}, {"authorId": "7642679", "name": "Daming + Gao"}, {"authorId": "143971134", "name": "P. Tsou"}, {"authorId": "40383426", + "name": "Wenjian Gan"}, {"authorId": "5380009", "name": "A. Papa"}, {"authorId": + "145266603", "name": "B. Kim"}, {"authorId": "49048640", "name": "L. Wan"}, + {"authorId": "2116287366", "name": "Amrik J Singh"}, {"authorId": "1859720", + "name": "B. Zhai"}, {"authorId": "49059923", "name": "M. Yuan"}, {"authorId": + "2108288335", "name": "Zhiwei Wang"}, {"authorId": "2665934", "name": "S. + Gygi"}, {"authorId": "145569223", "name": "T. Lee"}, {"authorId": "1715537", + "name": "K. Lu"}, {"authorId": "145751285", "name": "A. Toker"}, {"authorId": + "4499580", "name": "P. Pandolfi"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "40294231", "name": "M. Kirschner"}, {"authorId": "4616798", + "name": "P. Sicinski"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144084152", "name": "Wenyi Wei"}]}, {"paperId": "0647d51fc33aeab20313d9101612c311dacb278c", + "externalIds": {"MAG": "2142747850", "DOI": "10.1158/0008-5472.CAN-13-0544", + "CorpusId": 12575363, "PubMed": "24322983"}, "corpusId": 12575363, "publicationVenue": + {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", "name": "Cancer Research", + "type": "journal", "alternate_names": ["Cancer Res"], "issn": "0008-5472", + "url": "https://cancerres.aacrjournals.org/", "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/0647d51fc33aeab20313d9101612c311dacb278c", + "title": "A genetic mouse model of invasive endometrial cancer driven by concurrent + loss of Pten and Lkb1 Is highly responsive to mTOR inhibition.", "abstract": + "Signals from the tumor suppressors PTEN and LKB1 converge on mTOR to negatively + regulate its function in cancer cells. Notably, both of these suppressors + are attenuated in a significant fraction of human endometrial tumors. In this + study, we generated a genetic mouse model of endometrial cancer driven by + concomitant loss of these suppressors to gain pathophysiological insight into + this disease. Dual loss of Pten and Lkb1 in the endometrial epithelium led + to rapid development of advanced endometrioid endometrial tumors with 100% + penetrance and short host survival. The tumors displayed dysregulated phosphatidylinositol + 3-kinase (PI3K)/Akt and Lkb1/Ampk signaling with hyperactivation of mTOR signaling. + Treatment with a dual PI3K/mTOR inhibitor, BEZ235, extended the time before + tumor onset and prolonged overall survival. The PI3K inhibitor GDC-0941 used + as a single agent reduced the growth rate of primary tumor implants in Pten/Lkb1-deficient + mice, and the mTOR inhibitor RAD001 was unexpectedly as effective as BEZ235 + in triggering tumor regression. In parallel, we also found that ectopic expression + of LKB1 in PTEN/LKB1-deficient human endometrial cancer cells increased their + sensitivity to PI3K inhibition. Together, our results demonstrated that Pten/Lkb1-deficient + endometrial tumors rely strongly on deregulated mTOR signaling, and they provided + evidence that LKB1 status may modulate the response of PTEN-deficient tumors + to PI3K or mTOR inhibitors.", "venue": "Cancer Research", "year": 2014, "referenceCount": + 43, "citationCount": 50, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3982380?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "74 1", "pages": "\n 15-23\n ", + "name": "Cancer research"}, "authors": [{"authorId": "7915457", "name": "Hailing + Cheng"}, {"authorId": "7476152", "name": "Pixu Liu"}, {"authorId": "2153304992", + "name": "Fan Zhang"}, {"authorId": "3802555", "name": "Erbo Xu"}, {"authorId": + "5740177", "name": "Lynn Symonds"}, {"authorId": "38628965", "name": "Carolynn + E Ohlson"}, {"authorId": "40803408", "name": "R. Bronson"}, {"authorId": "144301795", + "name": "S. Maira"}, {"authorId": "47366765", "name": "E. di Tomaso"}, {"authorId": + "2108996618", "name": "Jane Li"}, {"authorId": "6324437", "name": "A. Myers"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2241330", "name": + "G. Mills"}, {"authorId": "50985038", "name": "Jean J. Zhao"}]}, {"paperId": + "1247bbe2fbf3a552eae01b15d2190a31246133bb", "externalIds": {"MAG": "2781816664", + "DOI": "10.1016/J.CMET.2014.11.009", "CorpusId": 90157920}, "corpusId": 90157920, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/1247bbe2fbf3a552eae01b15d2190a31246133bb", + "title": "Erratum: BRD7 regulates XBP1s'' activity and glucose homeostasis + through its interaction with the regulatory subunits of pi3k (Cell Metabolism + (2014:20:73-84))", "abstract": null, "venue": "", "year": 2014, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1550413114005063/pdf", + "status": null}, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "20", + "name": "Cell Metabolism"}, "authors": [{"authorId": "48079845", "name": "S. + Park"}, {"authorId": "5718734", "name": "H. Herrema"}, {"authorId": "2070687289", + "name": "Mario Salazar"}, {"authorId": "4196414", "name": "I. \u00c7ak\u0131r"}, + {"authorId": "12159303", "name": "Serkan Cabi"}, {"authorId": "89884476", + "name": "F. Sahin"}, {"authorId": "47591147", "name": "Y. Chiu"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3088608", "name": "U. Ozcan"}]}, + {"paperId": "35c85036360e82c8e5b159b341ed41e2d9e8b5f8", "externalIds": {"MAG": + "1983001241", "DOI": "10.1016/j.molcel.2014.02.016", "CorpusId": 5588516, + "PubMed": "24657164"}, "corpusId": 5588516, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/35c85036360e82c8e5b159b341ed41e2d9e8b5f8", + "title": "BRD7, a tumor suppressor, interacts with p85\u03b1 and regulates + PI3K activity.", "abstract": null, "venue": "Molecules and Cells", "year": + 2014, "referenceCount": 39, "citationCount": 66, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276514001610/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2014-04-10", "journal": {"volume": + "54 1", "pages": "\n 193-202\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "47591147", "name": "Y. Chiu"}, {"authorId": "46663676", + "name": "Jennifer Y. Lee"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "377964faa0f929470f7ede2faa3b4789be4e36fe", "externalIds": {"MAG": + "2072528662", "DOI": "10.1056/NEJMe1400055", "CorpusId": 205078499, "PubMed": + "24620870"}, "corpusId": 205078499, "publicationVenue": {"id": "dc31f077-7737-4e33-baa3-bceeff44ec27", + "name": "New England Journal of Medicine", "type": "journal", "alternate_names": + ["n engl J Med", "The New England Journal of Medicine", "N Engl J Med"], "issn": + "0028-4793", "url": "https://www.nejm.org/", "alternate_urls": ["http://www.nejm.org/content/index.asp", + "http://www.nejm.org/"]}, "url": "https://www.semanticscholar.org/paper/377964faa0f929470f7ede2faa3b4789be4e36fe", + "title": "Idelalisib--a PI3K\u03b4 inhibitor for B-cell cancers.", "abstract": + "The phosphoinositide 3-kinase (PI3K) signal transduction pathway is highly + active in tumors and drives many of the hallmarks of cancer. Efforts to develop + PI3K inhibitors for oncology have been complicated by the existence of four + distinct PI3K catalytic isoforms with partially overlapping functions. In + addition, diverse resistance mechanisms and on-target toxic effects have been + observed with many PI3K inhibitors.1,2 In this issue of the Journal, two clinical + teams report that idelalisib, a selective inhibitor of the delta isoform of + PI3K, provides impressive efficacy and has an acceptable side-effect profile + when used to treat patients with certain B-cell cancers.3, .\u00a0.\u00a0.", + "venue": "New England Journal of Medicine", "year": 2014, "referenceCount": + 10, "citationCount": 73, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "https://escholarship.org/content/qt6f3592b4/qt6f3592b4.pdf?t=p5xypb", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["LettersAndComments", + "Editorial"], "publicationDate": "2014-03-12", "journal": {"volume": "370 + 11", "pages": "\n 1061-2\n ", "name": "The New England journal + of medicine"}, "authors": [{"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "472c57895e0b6d38e507cc6a4b649c1e5f857060", + "externalIds": {"MAG": "2181833926", "CorpusId": 97972389}, "corpusId": 97972389, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/472c57895e0b6d38e507cc6a4b649c1e5f857060", + "title": "Homeostasis Enzyme Bifunctionality in Glucose Switching and Its + Circumvention by A Fundamental Trade-off in Covalent Computational Biology:", + "abstract": null, "venue": "", "year": 2014, "referenceCount": 58, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "name": ""}, "authors": [{"authorId": "2163633", "name": "J. Gunawardena"}, + {"authorId": "93256439", "name": "W. Locasale"}, {"authorId": "8319448", "name": + "U. Alon"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2055333220", + "name": "A. Owen"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "47425181", "name": "D. Croll"}]}, {"paperId": "56ad1278219c9b7d2d716e17a9b4ffafd3e4f903", + "externalIds": {"MAG": "2039815737", "DOI": "10.1016/j.cmet.2014.04.006", + "CorpusId": 206842632, "PubMed": "24836559"}, "corpusId": 206842632, "publicationVenue": + {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", "name": "Cell Metabolism", + "type": "journal", "alternate_names": ["Cell Metab"], "issn": "1550-4131", + "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": ["http://www.sciencedirect.com/science/journal/15504131", + "http://www.cellmetabolism.org/"]}, "url": "https://www.semanticscholar.org/paper/56ad1278219c9b7d2d716e17a9b4ffafd3e4f903", + "title": "BRD7 regulates XBP1s'' activity and glucose homeostasis through + its interaction with the regulatory subunits of PI3K.", "abstract": null, + "venue": "Cell Metabolism", "year": 2014, "referenceCount": 57, "citationCount": + 53, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1550413114001703/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2014-07-01", "journal": {"volume": "20 1", "pages": "\n 73-84\n ", + "name": "Cell metabolism"}, "authors": [{"authorId": "48079845", "name": "S. + Park"}, {"authorId": "5718734", "name": "H. Herrema"}, {"authorId": "2070687289", + "name": "Mario Salazar"}, {"authorId": "4196414", "name": "I. \u00c7ak\u0131r"}, + {"authorId": "12159303", "name": "Serkan Cabi"}, {"authorId": "1399526925", + "name": "Fatma Basibuyuk Sahin"}, {"authorId": "47591147", "name": "Y. Chiu"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3088608", "name": + "U. Ozcan"}]}, {"paperId": "7b31cd007923278d21894116e2ab886e14420463", "externalIds": + {"MAG": "2033347288", "DOI": "10.1158/1538-7445.AM2014-2951", "CorpusId": + 84252448}, "corpusId": 84252448, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7b31cd007923278d21894116e2ab886e14420463", + "title": "Abstract 2951: Vitamin C is selectively toxic to cancer cells harboring + KRAS or BRAF mutations by targeting GAPDH", "abstract": "Although more than + half of colorectal cancer patients have either KRAS or BRAF mutations, targeted + therapies for these subgroups of cancer patients are still lacking. Here, + we report that KRAS or BRAF mutant cells exhibit a significant increase in + the uptake of oxidized vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose + transporter. Increased uptake of DHA in the mutant cell lines causes oxidative + stress as intracellular DHA is immediately reduced back to vitamin C by reduced + glutathione. Elevated reactive oxygen species inactivate GAPDH and thus divert + glycolytic flux into the pentose phosphate pathway. Because KRAS or BRAF mutant + cells are highly dependent on glycolysis, this altered glucose metabolism + induced by vitamin C ultimately leads to an energy deficit in KRAS or BRAF + mutant cells and thereby cell death. There are currently a growing number + of clinical trials in phases I/II examining the effect of high dose vitamin + C as a treatment for cancers, including colorectal cancers. Our results provide + a rationale for the pharmacological use of vitamin C as a therapeutic agent + to treat colorectal cancer patients with oncogenic KRAS or BRAF mutations. + Citation Format: Jihye Yun, Adam Kavalier, Edouard Mullarky, Kaitlyn Bosch, + Jatin Roper, Carlo Rago, Jihye Paik, John Asara, Steven Gross, Bert Vogelstein, + Nickolas Papadopoulos, Lewis Cantley. Vitamin C is selectively toxic to cancer + cells harboring KRAS or BRAF mutations by targeting GAPDH. [abstract]. In: + Proceedings of the 105th Annual Meeting of the American Association for Cancer + Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res + 2014;74(19 Suppl):Abstract nr 2951. doi:10.1158/1538-7445.AM2014-2951", "venue": + "", "year": 2014, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2014-10-01", "journal": {"volume": "74", "pages": "2951-2951", "name": "Cancer + Research"}, "authors": [{"authorId": "40164091", "name": "Jihye Yun"}, {"authorId": + "8391227", "name": "A. Kavalier"}, {"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "7881810", "name": "Kaitlyn Bosch"}, {"authorId": + "145864068", "name": "J. Roper"}, {"authorId": "1907762", "name": "C. Rago"}, + {"authorId": "5056578", "name": "J. Paik"}, {"authorId": "3028470", "name": + "J. Asara"}, {"authorId": "5769141", "name": "S. Gross"}, {"authorId": "1965563", + "name": "B. Vogelstein"}, {"authorId": "144798543", "name": "N. Papadopoulos"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "7bb66463c955606250fc60b2c1e0b3ffc33657f8", + "externalIds": {"MAG": "2043603122", "DOI": "10.1016/j.cell.2014.12.009", + "CorpusId": 54566844, "PubMed": "25525870"}, "corpusId": 54566844, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/7bb66463c955606250fc60b2c1e0b3ffc33657f8", + "title": "Acetate Fuels the Cancer Engine", "abstract": null, "venue": "Cell", + "year": 2014, "referenceCount": 8, "citationCount": 39, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867414015797/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2014-12-18", "journal": {"volume": + "159", "pages": "1492-1494", "name": "Cell"}, "authors": [{"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "7be5527d516c79561eef8378c3db84ddaeedcfd0", "externalIds": {"MAG": + "2090449329", "DOI": "10.1074/jbc.M113.546515", "CorpusId": 12600062, "PubMed": + "24634222"}, "corpusId": 12600062, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/7be5527d516c79561eef8378c3db84ddaeedcfd0", + "title": "A Fundamental Trade-off in Covalent Switching and Its Circumvention + by Enzyme Bifunctionality in Glucose Homeostasis*", "abstract": "Background: + Covalent modification cycles are widely used as regulatory switches. Results: + Mathematical analysis reveals, under very general assumptions, an unavoidable + trade-off between switching efficiency and cell-to-cell coherence. Conclusion: + Enzyme bifunctionality offers a way to circumvent this trade-off. Significance: + This may explain the bifunctionality of PFK-2/FBPase-2 in controlling the + switch between glycolysis and gluconeogenesis in the mammalian liver. Covalent + modification provides a mechanism for modulating molecular state and regulating + physiology. A cycle of competing enzymes that add and remove a single modification + can act as a molecular switch between \u201con\u201d and \u201coff\u201d and + has been widely studied as a core motif in systems biology. Here, we exploit + the recently developed \u201clinear framework\u201d for time scale separation + to determine the general principles of such switches. These methods are not + limited to Michaelis-Menten assumptions, and our conclusions hold for enzymes + whose mechanisms may be arbitrarily complicated. We show that switching efficiency + improves with increasing irreversibility of the enzymes and that the on/off + transition occurs when the ratio of enzyme levels reaches a value that depends + only on the rate constants. Fluctuations in enzyme levels, which habitually + occur due to cellular heterogeneity, can cause flipping back and forth between + on and off, leading to incoherent mosaic behavior in tissues, that worsens + as switching becomes sharper. This trade-off can be circumvented if enzyme + levels are correlated. In particular, if the competing catalytic domains are + on the same protein but do not influence each other, the resulting bifunctional + enzyme can switch sharply while remaining coherent. In the mammalian liver, + the switch between glycolysis and gluconeogenesis is regulated by the bifunctional + 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2). We + suggest that bifunctionality of PFK-2/FBPase-2 complements the metabolic zonation + of the liver by ensuring coherent switching in response to insulin and glucagon.", + "venue": "Journal of Biological Chemistry", "year": 2014, "referenceCount": + 69, "citationCount": 35, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/289/19/13010.full.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2014-03-14", "journal": + {"volume": "289", "pages": "13010 - 13025", "name": "The Journal of Biological + Chemistry"}, "authors": [{"authorId": "32933502", "name": "T. Dasgupta"}, + {"authorId": "47425181", "name": "D. Croll"}, {"authorId": "38261902", "name": + "J. Owen"}, {"authorId": "3804233", "name": "M. V. Vander Heiden"}, {"authorId": + "2268976", "name": "J. Locasale"}, {"authorId": "8319448", "name": "U. Alon"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2163633", "name": + "J. Gunawardena"}]}, {"paperId": "7e218d5e3469b90fc1f0e4328fdc3bc50d1352c2", + "externalIds": {"DOI": "10.1186/1741-7007-12-8", "CorpusId": 255830136}, "corpusId": + 255830136, "publicationVenue": {"id": "1617f5c3-5410-462d-91c9-7aa8ced2d91d", + "name": "BMC Biology", "type": "journal", "issn": "1741-7007", "url": "http://www.biomedcentral.com/1741-7007/", + "alternate_urls": ["http://www.biomedcentral.com/bmcbiol/", "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=215"]}, + "url": "https://www.semanticscholar.org/paper/7e218d5e3469b90fc1f0e4328fdc3bc50d1352c2", + "title": "Cancer, metabolism, fructose, artificial sweeteners, and going cold + turkey on sugar", "abstract": null, "venue": "BMC Biology", "year": 2014, + "referenceCount": 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://bmcbiol.biomedcentral.com/track/pdf/10.1186/1741-7007-12-8", + "status": null}, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Agricultural + And Food Sciences", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2014-01-31", "journal": {"volume": "12", "name": "BMC + Biology"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "819eeeb41f6e84dd5c00221a269e91238736c4ad", "externalIds": {"MAG": "2023300506", + "DOI": "10.1038/nature13611", "CorpusId": 4411762, "PubMed": "25119024"}, + "corpusId": 4411762, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/819eeeb41f6e84dd5c00221a269e91238736c4ad", + "title": "Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial + function", "abstract": null, "venue": "Nature", "year": 2014, "referenceCount": + 127, "citationCount": 889, "influentialCitationCount": 36, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc4376130?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2014-10-30", "journal": {"volume": + "514", "pages": "628-632", "name": "Nature"}, "authors": [{"authorId": "49837367", + "name": "A. Viale"}, {"authorId": "47110079", "name": "P. Pettazzoni"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "33312849", "name": "H. Ying"}, + {"authorId": "3461293", "name": "Nora S. Sanchez"}, {"authorId": "48455352", + "name": "M. Marchesini"}, {"authorId": "8457336", "name": "A. Carugo"}, {"authorId": + "39319755", "name": "T. Green"}, {"authorId": "4288735", "name": "S. Seth"}, + {"authorId": "8048176", "name": "V. Giuliani"}, {"authorId": "1397847396", + "name": "M. Kost\u2010Alimova"}, {"authorId": "35482259", "name": "F. Muller"}, + {"authorId": "3923755", "name": "S. Colla"}, {"authorId": "6715637", "name": + "L. Nezi"}, {"authorId": "50992424", "name": "G. Genovese"}, {"authorId": + "8506554", "name": "Angela Deem"}, {"authorId": "4243353", "name": "A. Kapoor"}, + {"authorId": "8195225", "name": "W. Yao"}, {"authorId": "5884636", "name": + "Emanuela Brunetto"}, {"authorId": "78102197", "name": "Ya''an Kang"}, {"authorId": + "49059923", "name": "M. Yuan"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "49416094", "name": "Y. A. Wang"}, {"authorId": "3095168", "name": + "T. Heffernan"}, {"authorId": "4668673", "name": "A. Kimmelman"}, {"authorId": + "2109007858", "name": "Huamin Wang"}, {"authorId": "144926646", "name": "J. + Fleming"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5593407", + "name": "R. DePinho"}, {"authorId": "5336286", "name": "G. Draetta"}]}, {"paperId": + "9efbb965cc8fbca5663d9ecab0b5e42a8b2d8ba6", "externalIds": {"PubMedCentral": + "4073055", "MAG": "1986963380", "DOI": "10.1186/2049-3002-2-S1-P86", "CorpusId": + 71710356}, "corpusId": 71710356, "publicationVenue": {"id": "787ea3c5-4d66-450c-b13d-9f7934429b7f", + "name": "Cancer & Metabolism", "type": "journal", "alternate_names": ["Cancer + Metab", "Cancer and Metabolism", "Cancer Metab"], "issn": "2049-3002", "url": + "http://www.cancerandmetabolism.com/"}, "url": "https://www.semanticscholar.org/paper/9efbb965cc8fbca5663d9ecab0b5e42a8b2d8ba6", + "title": "Phosphoinositide 3-Kinase regulates glycolysis through mobilization + of Aldolase A from the actin cytoskeleton", "abstract": null, "venue": "Cancer + & Metabolism", "year": 2014, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://cancerandmetabolism.biomedcentral.com/track/pdf/10.1186/2049-3002-2-S1-P86", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2014-05-28", "journal": {"volume": + "2", "pages": "P86 - P86", "name": "Cancer & Metabolism"}, "authors": [{"authorId": + "113164867", "name": "Hai Hu"}, {"authorId": "49149990", "name": "Ashish Juvekar"}, + {"authorId": "88857753", "name": "Costas Lyssiotis"}, {"authorId": "2791479", + "name": "J. Albeck"}, {"authorId": "6482179", "name": "D. Tolan"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "31554501", "name": "G. Wulf"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "a489eaaf35ec9925cb192db96a3669c7ff73df8d", + "externalIds": {"MAG": "2074492690", "DOI": "10.1158/1538-7445.AM2014-CT338", + "CorpusId": 72756487}, "corpusId": 72756487, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/a489eaaf35ec9925cb192db96a3669c7ff73df8d", + "title": "Abstract CT338: Combination of a PI3K- and a PARP-inhibitor to treat + high-grade serous ovarian or triple-negative breast cancer", "abstract": "Proceedings: + AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA\n\nClinical trials + have shown promising responses of BRCA-linked breast and ovarian cancers to + PARP inhibitor therapy, but remissions are often short-lived and incomplete. + The PI3K pathway is frequently activated in these malignancies. Recently, + we reported in vivo synergy of a PI3K- and a PARP-inhibitor in a mouse model + of BRCA1-related breast cancer. While the PARP-inhibitor olaparib alone attenuated + tumor growth modestly, a dramatic reduction in tumor growth was observed when + olaparib was combined with the PI3K-inhibitor BKM120. In BRCA1-mutant HCC1937 + BC cells, PI3K- (but not akt-) inhibition increased indicators of DNA damage, + such as poly-ADP-ribosylation and \u03b3H2AX, suggesting a critical role of + PI3K activity for the maintenance of genomic stability. Here, we report on + the molecular mechanism underlying this synergy, on treatment outcomes in + an improved mouse model system and the development of an early-phase clinical + study. Pre-clinical modeling was done in BRCA1-mutant HCC1937 cells and in + a mouse model based on the syngenic transplantation of tumors derived on the + K14-Cre BRCA1f/fp53f/f background. Metabolic profiling in vitro and in vivo + showed that PI3K-inhibition decreased flux through glycolysis and specifically + through the non-oxidative pentose-phosphate pathway, the main source of ribose-5-phosphate + required for the de novo synthesis of nucleotides in HCC1937 cells. Within + 3 hours and preceding cell cycle changes, BKM120 caused a decrease in nucleotide + pools that was further exacerbated by the addition of olaparib. Nucleotide + shortage led to to replication stress with the appearance of \u03b3H2AX and + increased poly-ADP-ribosylation. Tumors with complete loss of BRCA1 and p53 + proved particularly vulnerable to this treatment strategy. We were able to + induce complete and durable remissions of murine tumors arising on the K14-Cre + BRCA1f/fp53f/f background with a 28-day course of BKM120 and Olaparib. These + preclinical data have served as the rationale for a phase I, multi-center + study ([NCT01623349][1]) combining the oral PARP inhibitor olaparib with the + oral PI3-kinase inhibitor BKM120 in patients with recurrent HGSC or recurrent + TNBC. The study is being conducted through the Stand Up to Cancer (SU2C)''s + Targeting PI3-kinase in Women''s Cancers Dream Team. It has a 3 + 3 design, + escalating if 0/3 or 1/6 participants have a DLT during the first cycle of + therapy. The study objectives are to determine the recommended phase II dose + (RP2D) of daily continuous oral olaparib (using the tablet formulation) and + BKM120, assess toxicities, safety, and preliminary activity of this combination, + and determine pharmacokinetic profiles of both agents as well as translational + endpoints. The study serves as an example for the development of a clinical + trials concept for TNBC and HGSC based on a close collaboration of basic and + clinical scientists through the SU2C mechanism.\n\nCitation Format: Gerburg + M. Wulf, Ashish Juvekar, Costas A. Lyssiotis, Hai Hu, Sina Yadegarynia, Hui + Liu, Baek Kim, Eric Winter, Ralph Scully, John Asara, Lewis C. Cantley, Ursula + Matulonis. Combination of a PI3K- and a PARP-inhibitor to treat high-grade + serous ovarian or triple-negative breast cancer. [abstract]. In: Proceedings + of the 105th Annual Meeting of the American Association for Cancer Research; + 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 + Suppl):Abstract nr CT338. doi:10.1158/1538-7445.AM2014-CT338\n\n [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01623349&atom=%2Fcanres%2F74%2F19_Supplement%2FCT338.atom", + "venue": "", "year": 2014, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2014-10-01", "journal": {"volume": "74", "name": "Cancer Research"}, "authors": + [{"authorId": "31554501", "name": "G. Wulf"}, {"authorId": "49149990", "name": + "Ashish Juvekar"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "113164867", "name": "Hai Hu"}, {"authorId": "3893473", "name": "S. Yadegarynia"}, + {"authorId": "2146671919", "name": "Hui Liu"}, {"authorId": "2144570709", + "name": "Baek Kim"}, {"authorId": "2052370549", "name": "Eric P Winter"}, + {"authorId": "143905392", "name": "R. Scully"}, {"authorId": "3028470", "name": + "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6927295", + "name": "U. Matulonis"}]}, {"paperId": "b132df46f298d8e45cb2bc30121b7f6b64c86710", + "externalIds": {"CorpusId": 207786498}, "corpusId": 207786498, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b132df46f298d8e45cb2bc30121b7f6b64c86710", + "title": "compound PARP / PI 3 K inhibition Vulnerabilities of PTEN-p 53-deficient + prostate cancers to", "abstract": null, "venue": "", "year": 2014, "referenceCount": + 22, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "1398122926", + "name": "E. Gonzalez-Billalabeitia"}, {"authorId": "3793357", "name": "N. + Seitzer"}, {"authorId": "9673009", "name": "S. Song"}, {"authorId": "2967391", + "name": "M. Song"}, {"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "8015447", "name": "Xue-Song Liu"}, {"authorId": "4276612", "name": "M. Epping"}, + {"authorId": "5380009", "name": "A. Papa"}, {"authorId": "4584039", "name": + "R. Hobbs"}, {"authorId": "48622732", "name": "Ming Chen"}, {"authorId": "5729169", + "name": "A. Lunardi"}, {"authorId": "6294709", "name": "Christopher Ng"}, + {"authorId": "4817196", "name": "Kaitlyn A. Webster"}, {"authorId": "7505152", + "name": "S. Signoretti"}, {"authorId": "6213932", "name": "M. Loda"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "3547827", "name": "C. Nardella"}, + {"authorId": "4102988", "name": "J. Clohessy"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4499580", "name": "P. Pandolfi"}]}, {"paperId": + "b42ae6209615380e956f59664c07ef312278a511", "externalIds": {"MAG": "2318414253", + "DOI": "10.1016/S0959-8049(14)50626-0", "CorpusId": 75309643}, "corpusId": + 75309643, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/b42ae6209615380e956f59664c07ef312278a511", + "title": "708: A Phase Ib study of BKM120 combined with abiraterone acetate + for castrate-resistant, metastatic prostate cancer", "abstract": null, "venue": + "", "year": 2014, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2014-07-01", "journal": {"volume": "50", "name": "European Journal of Cancer"}, + "authors": [{"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": "35208382", + "name": "J. Kung"}, {"authorId": "2110420120", "name": "Jim S. Wu"}, {"authorId": + "6213932", "name": "M. Loda"}, {"authorId": "9933602", "name": "P. Kantoff"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6189162", "name": + "S. Balk"}, {"authorId": "5854981", "name": "G. Bubley"}]}, {"paperId": "b962f20d916814950d2b094c1a5827f43552ce7c", + "externalIds": {"MAG": "2549508308", "DOI": "10.1182/BLOOD.V124.21.SCI-43.SCI-43", + "CorpusId": 89398284}, "corpusId": 89398284, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/b962f20d916814950d2b094c1a5827f43552ce7c", + "title": "Maintenance of Pluripotent Stem Cells is Influenced by Ser/Thr Metabolism", + "abstract": "Recent studies have suggested not only that stem cells have different + metabolic requirements than terminally differentiated cells, but also that + metabolic intermediates may play a role in the maintenance of stem cells. + It has long been clear that changes in acetylation and methylation of histones, + as well as methylation of DNA play critical roles in deciding cell fate. The + availability of critical intermediates in metabolism, especially S-adenosylmethionine + (SAM), acetyl-CoA, nicotinamide adenine dinucleotide (NAD) and a-ketoglutarate + play critical roles in modulating acetylation and methylation of histones + and methylation of DNA. In the course of evaluating an unusual requirement + of threonine (Thr) for the growth of murine embryonic stem cells, we found + that metabolism of Thr to glycine (Gly) and the subsequent use of the methyl + group of Gly for converting homocysteine to methionine is critical for maintaining + high levels of SAM and low levels of S-adenosyl-homocysteine. Importantly, + depletion of Thr from the media resulted in decreased tri-methylation of histone + H3 lysine-4 (H3K4me3), leading to slowed growth and increased differentiation. + Thus, abundance of SAM appears to influence H3K4me3, providing a possible + mechanism by which modulation of a metabolic pathway might influence stem + cell fate. Demethylation of histones and DNA can also be controlled by metabolic + intermediates. Mutated forms of isocitrate dehydrogenase 1 (IDH1) and IDH2 + that drive acute myeloid leukemia (AML) and other cancers, produce an oncometabolite + (2-hydrogyglutarate) that can compete with the a-ketoglutarate requirement + for enzymes involved in hydroxy-methylation and subsequent demethylation of + DNA and histones. Recent studies indicate that 2-hydroxyglutarate plays a + role in blocking differentiation of cancer cells. These and other observations + linking intermediates in metabolism to stem cell maintenance will be discussed. + Disclosures Cantley: Agios Pharmaceuticals: Consultancy, Equity Ownership, + Membership on an entity9s Board of Directors or advisory committees, Patents + & Royalties.", "venue": "", "year": 2014, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2014-12-06", "journal": {"volume": + "124", "name": "Blood"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "bc73862e981532143100310831ed8bc48af1d72e", "externalIds": {"MAG": + "569508431", "DOI": "10.5860/choice.186287", "CorpusId": 82078242}, "corpusId": + 82078242, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/bc73862e981532143100310831ed8bc48af1d72e", + "title": "Signal transduction : principles, pathways, and processes", "abstract": + "This is a free sample of content from Signal Transduction. Click here for + more information on how to buy the book. Summary: \" This textbook provides + a comprehensive view of signal transduction, covering both the fundamental + mechanisms involved and their roles in key biological processes. It first + lays out the basic principles of signal transduction, explaining how different + receptors receive information and transmit it via signaling proteins, ions, + and second messengers. It then surveys the major signaling pathways that operate + in cells, before examining in detail how these function in processes such + as cell growth and division, cell movement, metabolism, development, reproduction, + the nervous system, and immune function \" \u2013 Provided by publisher. Includes + bibliographical references and index. All World Wide Web addresses are accurate + to the best of our knowledge at the time of printing. Authorization to photocopy + items for internal or personal use, or the internal or personal use of specific + clients, is granted by Cold Spring Harbor Laboratory Press, provided that + the appropriate fee is paid directly to the Copyright Clearance Center (CCC). + Write or call CCC at 222 Rosewood Drive, Danvers, MA 01923 (978-750-8400) + for information about fees and regulations. Prior to photocopying items for + educational classroom use, contact CCC at the above address. Additional information + on CCC can be obtained at CCC Online at www.copyright.com. This book is dedicated + to the memory of Tony Pawson (1952 \u20132013). Tony was a giant in the field + of signal transduction, who established principles of protein \u2013protein + interactions that have profoundly influenced our understanding of signal transduction. + His enduring legacy will be the discovery that the Src homology 2 (SH2) domain + of one protein can selectively interact with a tyrosine residue in a second + protein, once it is phosphorylated in response to an upstream signal. This + type of inducible protein \u2013 protein interaction can link intracellu-lar + signals generated in response to various upstream stimuli to downstream signaling + events. This insight was the basis for his enormously influential idea that + eukaryotic signal-ing systems involve modular and combinatorial interaction + domains that propagate signals throughout the cell.", "venue": "", "year": + 2014, "referenceCount": 0, "citationCount": 23, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review"], "publicationDate": + null, "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "bc8011fa978b52b8c651ca7d2921fe814b00b59d", + "externalIds": {"MAG": "2050593017", "DOI": "10.1158/1538-7445.AM2014-CT418", + "CorpusId": 71733885}, "corpusId": 71733885, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/bc8011fa978b52b8c651ca7d2921fe814b00b59d", + "title": "Abstract CT418: A Phase Ib study of BKM120 combined with abiraterone + acetate for castrate-resistant, metastatic prostate cancer", "abstract": "Introduction: + There is significant cross-talk between PI3-kinase (PI3K) and androgen receptor + (AR) signaling pathways, respectively, which are both critical for cell survival + in castrate-resistant prostate cancer (CRPC). The primary study objective + (NCT01741753) is to determine the safety profile and maximum tolerated dose + (MTD) of BKM120 (pan-PI3K inhibitor) in combination with abiraterone/prednisone + (A/P) in CRPC patients. The secondary study objectives are to assess the impact + of PTEN status on duration of response/time to progression in the expansion + cohort, and to evaluate the impact of BKM120 on a PI3-kinase activation fingerprint + in metastatic bone or lymph node tissue samples. An exploratory objective + of the study is to assess the effect of BKM120 on transcription of a set of + AR-regulated genes in metastatic bone biopsy samples. Methods: The trial design + involves a 14 day lead-in phase with BKM120 alone, to assess single-agent + toxicity and perform correlative studies. A/P is combined with BKM120 at the + end of 14 days using the standard 3+3 dose-escalation design with 3 dose levels + of BKM120 (80 mg, 100 mg, 120 mg, respectively), and participants are assessed + for safety and MTD on the combination therapy. To determine pharmacodynamic + impact of single agent BKM120 on the PI3K activation signature at a metastatic + site, a mandatory CT-guided bone or lymph node biopsy is performed prior to + BKM120 initiation and at the end of 2 weeks on BKM120 single-agent therapy. + Immunohistochemical (IHC) stains for three markers (p-AKT, p-S6 and PTEN) + are used to obtain a semi-quantitative PI3K activation score, based on the + quartile levels of continuous staining scores of each marker. Results: The + clinical, PSA biochemical responses, immunohistochemical and molecular RT-PCR + data for three enrolled patients are summarized here. The first patient had + symptomatic bone pain with limited functional mobility at baseline, and was + treated with the first BKM120 dose level of 80 mg daily. He had a decline + in PSA from 156.5 to 129.6 during the lead-in phase with single-agent BKM120 + treatment with partial symptomatic pain relief. Interestingly, comparison + of pre- and post-treatment metastatic bone tumor IHC staining on single-agent + BKM120 showed inhibition of phospho-S6 staining. Upon adding A/P to BKM120 + treatment, he had a striking decline in his PSA to 23.3 within 1 week, which + reached a nadir of 9.2 within 4 weeks of combination therapy treatment. This + striking biochemical improvement corresponded to a marked decline in narcotic + pain requirements, increased mobility and quality-of-life. However, he developed + clinical, biochemical and radiographic disease progression after 4 cycles + of combination therapy treatment, so had to withdraw from study. The second + and third patient had a >90% biochemical improvement within 4 weeks of combination + therapy treatment and remain on study to date. To evaluate cross-talk between + AR and PI3K signaling in the bone microenvironment, RT-PCR analyses on pre- + and BKM120-treated bone biopsy samples were performed. The results showed + that the feedback relationship between PI3K and AR signaling are heterogeneous, + and dependent on the PTEN status of the tumor. Conclusion: The pan-PI3K inhibitor/abiraterone + combination is well-tolerated, and demonstrates promising anti-tumor activity + in CRPC patients. Citation Format: Akash Patnaik, Massimo Loda, Justin Kung, + Jim Wu, MaryEllen Taplin, Philip Kantoff, Lewis Cantley, Steven Balk, Glenn + Bubley. A Phase Ib study of BKM120 combined with abiraterone acetate for castrate-resistant, + metastatic prostate cancer. [abstract]. In: Proceedings of the 105th Annual + Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San + Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract + nr CT418. doi:10.1158/1538-7445.AM2014-CT418", "venue": "", "year": 2014, + "referenceCount": 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2014-10-01", + "journal": {"volume": "74", "name": "Cancer Research"}, "authors": [{"authorId": + "40501341", "name": "A. Patnaik"}, {"authorId": "6213932", "name": "M. Loda"}, + {"authorId": "35208382", "name": "J. Kung"}, {"authorId": "2110420120", "name": + "Jim S. Wu"}, {"authorId": "80786834", "name": "M. Taplin"}, {"authorId": + "9933602", "name": "P. Kantoff"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "6189162", "name": "S. Balk"}, {"authorId": "5854981", "name": + "G. Bubley"}]}, {"paperId": "c1cf8e9b4442b7d4ecabe79cf8ad8f872817485d", "externalIds": + {"MAG": "2772115384", "DOI": "10.1200/JCO.2014.32.15_SUPPL.2510", "CorpusId": + 80085275}, "corpusId": 80085275, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/c1cf8e9b4442b7d4ecabe79cf8ad8f872817485d", + "title": "Phase I study of oral BKM120 and oral olaparib for high-grade serous + ovarian cancer (HGSC) or triple-negative breast cancer (TNBC).", "abstract": + "2510 Background: In vivo synergy of the PI3-kinase inhibitor BKM120 and the + PARP inhibitor olaparib is seen using a mouse model of BRCA1-related breast + cancer (BrCa) and sporadic TNBC (Juvekar et al and Ibrahim et al, Cancer Discovery + 2012). The PI3kinase pathway is activated in both TNBC and HGSC (www.cancergenome.nih.gov). + Olaparib is active in HGSC and germlineBRCA mutation (gBRCAm) ovarian cancer + (OvCa) and gBRCAm BrCa. These data were the rationale for this phase I, multi-center + study (NCT01623349) combining BKM120 and olaparib in patients (pts) with recurrent + HGSC or TNBC. Methods: This study has a 3 + 3 design, escalating dose levels + (DL) if 0/3 or 1/6 pts have a dose limiting toxicity (DLT) during the first + cycle (1st 28 days). Objectives are to determine the MTD and RP2D of daily + oral olaparib (tablet formulation) and BKM120, assess toxicities, preliminary + activity of this combination, and PK profiles of both drugs. Planned translational + endpts include PI3kinase pathway effects, BRCA1 immunostain...", "venue": + "", "year": 2014, "referenceCount": 0, "citationCount": 37, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2014-05-20", "journal": {"volume": + "32", "pages": "2510-2510", "name": "Journal of Clinical Oncology"}, "authors": + [{"authorId": "6927295", "name": "U. Matulonis"}, {"authorId": "31554501", + "name": "G. Wulf"}, {"authorId": "2167106", "name": "M. Birrer"}, {"authorId": + "2974900", "name": "S. Westin"}, {"authorId": "15775381", "name": "P. Quy"}, + {"authorId": "1397923721", "name": "K. Bell-McGuinn"}, {"authorId": "12796173", + "name": "B. Lasonde"}, {"authorId": "122974814", "name": "C. Whalen"}, {"authorId": + "6128162", "name": "C. Aghajanian"}, {"authorId": "2344124", "name": "D. Solit"}, + {"authorId": "2241330", "name": "G. Mills"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2369378", "name": "E. Winer"}]}, {"paperId": + "c2c818d35ad6db3edb6899306e625a0e8a108d7d", "externalIds": {"MAG": "2580579348", + "DOI": "10.1016/j.cell.2014.07.048", "CorpusId": 8724666, "PubMed": "25215489"}, + "corpusId": 8724666, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/c2c818d35ad6db3edb6899306e625a0e8a108d7d", + "title": "Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis", + "abstract": null, "venue": "Cell", "year": 2014, "referenceCount": 65, "citationCount": + 254, "influentialCitationCount": 8, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867414010381/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2014-09-01", "journal": {"volume": "158", "pages": "1309-1323", + "name": "Cell"}, "authors": [{"authorId": "47906491", "name": "Ying-hua Wang"}, + {"authorId": "5553029", "name": "W. J. Israelsen"}, {"authorId": "47381858", + "name": "Dongjun Lee"}, {"authorId": "34345448", "name": "V. Yu"}, {"authorId": + "5100030", "name": "N. T. Jeanson"}, {"authorId": "3633091", "name": "C. Clish"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "5002337", "name": "D. Scadden"}]}, {"paperId": + "ca84197b3fbc7593676217cfd93cc6617e4aa6d0", "externalIds": {"MAG": "2060607801", + "DOI": "10.1016/j.cell.2013.11.049", "CorpusId": 18517653, "PubMed": "24529379"}, + "corpusId": 18517653, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/ca84197b3fbc7593676217cfd93cc6617e4aa6d0", + "title": "Spatial Control of the TSC Complex Integrates Insulin and Nutrient + Regulation of mTORC1 at the Lysosome", "abstract": null, "venue": "Cell", + "year": 2014, "referenceCount": 54, "citationCount": 631, "influentialCitationCount": + 59, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867414000129/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2014-02-13", "journal": {"volume": "156", "pages": "771-785", + "name": "Cell"}, "authors": [{"authorId": "49029161", "name": "S. Menon"}, + {"authorId": "7449887", "name": "Christian C. Dibble"}, {"authorId": "46679535", + "name": "G. Talbott"}, {"authorId": "2367206", "name": "G. Hoxhaj"}, {"authorId": + "6044723", "name": "Alexander J Valvezan"}, {"authorId": "2115843581", "name": + "Hidenori Takahashi"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2339651", "name": "B. Manning"}]}, {"paperId": "cd0d6917325bf9d09e15dd5cda895d675703870a", + "externalIds": {"MAG": "2170908060", "DOI": "10.1200/JCO.2013.54.0518", "CorpusId": + 24709027, "PubMed": "24663045"}, "corpusId": 24709027, "publicationVenue": + {"id": "a5913268-3957-484f-b41f-347b0ba23338", "name": "Journal of Clinical + Oncology", "type": "journal", "alternate_names": ["J Clin Oncol"], "issn": + "0732-183X", "url": "https://ascopubs.org/loi/jco", "alternate_urls": ["http://www.jco.org/", + "http://jco.ascopubs.org/"]}, "url": "https://www.semanticscholar.org/paper/cd0d6917325bf9d09e15dd5cda895d675703870a", + "title": "Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase + inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal + growth factor receptor 2-negative metastatic breast cancer.", "abstract": + "PURPOSE\nBuparlisib, an oral reversible inhibitor of all class I phosphoinositide-3-kinases, + has shown antitumoral activity against estrogen receptor (ER)-positive breast + cancer cell lines and xenografts, alone and with endocrine therapy. This phase + Ib study evaluated buparlisib plus letrozole''s safety, tolerability, and + preliminary activity in patients with metastatic ER-positive breast cancer + refractory to endocrine therapy.\n\n\nPATIENTS AND METHODS\nPatients received + letrozole and buparlisib in two different administration schedules. Outcomes + were assessed by standard solid-tumor phase I methods. [(18)F]fluorodeoxyglucose-positron + emission tomography/computed tomography ([(18)F]FDG-PET/CT) scans were done + at baseline and 2 weeks after treatment initiation. Tumor blocks were collected + for phosphoinositide-3-kinase pathway mutation analysis.\n\n\nRESULTS\nFifty-one + patients were allocated sequentially to continuous or intermittent (five on/two + off days) buparlisib administration on an every-4-week schedule. Buparlisib''s + maximum-tolerated dose (MTD) was 100 mg/d. Common drug-related adverse events + included \u2264 grade 2 hyperglycemia, nausea, fatigue, transaminitis, and + mood disorders. The clinical benefit rate (lack of progression \u2265 6 months) + among all patients treated at the MTD was 31%, including two objective responses + in the continuous dose arm. Of seven patients remaining on treatment \u2265 + 12 months, three had tumors with PIK3CA hot-spot mutation. Patients exhibiting + metabolic disease progression by [(18)F]FDG-PET/CT scan at 2 weeks progressed + rapidly on therapy.\n\n\nCONCLUSION\nThe letrozole and buparlisib combination + was safe, with reversible toxicities regardless of schedule administration. + Clinical activity was observed independent of PIK3CA mutation status. No metabolic + response by [(18)F]FDG-PET/CT scan at 2 weeks was associated with rapid disease + progression. Phase III trials of buparlisib and endocrine therapy in patients + with ER-positive breast cancer are ongoing.", "venue": "Journal of Clinical + Oncology", "year": 2014, "referenceCount": 33, "citationCount": 153, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3986383?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Study", + "JournalArticle", "ClinicalTrial"], "publicationDate": "2014-04-20", "journal": + {"volume": "32 12", "pages": "\n 1202-9\n ", "name": "Journal + of clinical oncology : official journal of the American Society of Clinical + Oncology"}, "authors": [{"authorId": "2346140", "name": "I. Mayer"}, {"authorId": + "2186029", "name": "V. Abramson"}, {"authorId": "4327978", "name": "S. Isakoff"}, + {"authorId": "144854481", "name": "A. Forero"}, {"authorId": "66935619", "name": + "J. Balko"}, {"authorId": "40266307", "name": "M. Kuba"}, {"authorId": "46945931", + "name": "M. Sanders"}, {"authorId": "34773169", "name": "J. Yap"}, {"authorId": + "6566244", "name": "A. D. Van den Abbeele"}, {"authorId": "2111151410", "name": + "Yisheng Li"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2369378", "name": "E. Winer"}, {"authorId": "2057460", "name": "C. Arteaga"}]}, + {"paperId": "ce33c563f50f42ab8154bf76fe6e53a2b954549a", "externalIds": {"MAG": + "2033319963", "PubMedCentral": "4073077", "DOI": "10.1186/2049-3002-2-S1-P44", + "CorpusId": 84257486}, "corpusId": 84257486, "publicationVenue": {"id": "787ea3c5-4d66-450c-b13d-9f7934429b7f", + "name": "Cancer & Metabolism", "type": "journal", "alternate_names": ["Cancer + Metab", "Cancer and Metabolism", "Cancer Metab"], "issn": "2049-3002", "url": + "http://www.cancerandmetabolism.com/"}, "url": "https://www.semanticscholar.org/paper/ce33c563f50f42ab8154bf76fe6e53a2b954549a", + "title": "Pancreatic cancers depend on a non-canonical glutamine metabolism + pathway", "abstract": null, "venue": "Cancer & Metabolism", "year": 2014, + "referenceCount": 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://cancerandmetabolism.biomedcentral.com/track/pdf/10.1186/2049-3002-2-S1-P44", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2014-05-28", "journal": {"volume": + "2", "pages": "P44 - P44", "name": "Cancer & Metabolism"}, "authors": [{"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "38313825", "name": "J. Son"}, + {"authorId": "5810602", "name": "J. Mancias"}, {"authorId": "33312849", "name": + "H. Ying"}, {"authorId": "4668673", "name": "A. Kimmelman"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "d59ac67aacc4f9eeb8d12ae9f08ad30076a94355", + "externalIds": {"MAG": "2169228223", "DOI": "10.1158/2159-8290.CD-13-0230", + "CorpusId": 9173254, "PubMed": "24866151"}, "corpusId": 9173254, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/d59ac67aacc4f9eeb8d12ae9f08ad30076a94355", + "title": "Vulnerabilities of PTEN-TP53-deficient prostate cancers to compound + PARP-PI3K inhibition.", "abstract": "UNLABELLED\nProstate cancer is the most + prevalent cancer in males, and treatment options are limited for advanced + forms of the disease. Loss of the PTEN and TP53 tumor suppressor genes is + commonly observed in prostate cancer, whereas their compound loss is often + observed in advanced prostate cancer. Here, we show that PARP inhibition triggers + a p53-dependent cellular senescence in a PTEN-deficient setting in the prostate. + Surprisingly, we also find that PARP-induced cellular senescence is morphed + into an apoptotic response upon compound loss of PTEN and p53. We further + show that superactivation of the prosurvival PI3K-AKT signaling pathway limits + the efficacy of a PARP single-agent treatment, and that PARP and PI3K inhibitors + effectively synergize to suppress tumorigenesis in human prostate cancer cell + lines and in a Pten/Trp53-deficient mouse model of advanced prostate cancer. + Our findings, therefore, identify a combinatorial treatment with PARP and + PI3K inhibitors as an effective option for PTEN-deficient prostate cancer.\n\n\nSIGNIFICANCE\nThe + paucity of therapeutic options in advanced prostate cancer displays an urgent + need for the preclinical assessment of novel therapeutic strategies. We identified + differential therapeutic vulnerabilities that emerge upon the loss of both + PTEN and p53, and observed that combined inhibition of PARP and PI3K provides + increased efficacy in hormone-insensitive advanced prostate cancer.", "venue": + "Cancer Discovery", "year": 2014, "referenceCount": 27, "citationCount": 74, + "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc4125493?pdf=render", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2014-05-27", "journal": + {"volume": "4 8", "pages": "\n 896-904\n ", "name": "Cancer + discovery"}, "authors": [{"authorId": "1398122926", "name": "E. Gonzalez-Billalabeitia"}, + {"authorId": "3793357", "name": "N. Seitzer"}, {"authorId": "9673009", "name": + "S. Song"}, {"authorId": "2967391", "name": "M. Song"}, {"authorId": "40501341", + "name": "A. Patnaik"}, {"authorId": "8015447", "name": "Xue-Song Liu"}, {"authorId": + "4276612", "name": "M. Epping"}, {"authorId": "5380009", "name": "A. Papa"}, + {"authorId": "4584039", "name": "R. Hobbs"}, {"authorId": "48622732", "name": + "Ming Chen"}, {"authorId": "5729169", "name": "A. Lunardi"}, {"authorId": + "6294709", "name": "Christopher Ng"}, {"authorId": "4817196", "name": "Kaitlyn + A. Webster"}, {"authorId": "7505152", "name": "S. Signoretti"}, {"authorId": + "6213932", "name": "M. Loda"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "3547827", "name": "C. Nardella"}, {"authorId": "4102988", "name": + "J. Clohessy"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4499580", "name": "P. Pandolfi"}]}, {"paperId": "d70fa8dfca0f230336c5fe00857ca539f3b0fd12", + "externalIds": {"MAG": "2072276834", "DOI": "10.1093/NEUONC/NOU242.33", "CorpusId": + 85200684}, "corpusId": 85200684, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d70fa8dfca0f230336c5fe00857ca539f3b0fd12", + "title": "CS-33 * DISCOVERY OF A p53-INDEPENDENT SUPPRESSOR OF SENESCENCE + OF GLIOBLASTOMA MULTIFORME", "abstract": "Glioblastoma multiforme (GBM) is + the most malignant brain tumor and resistant to cell senescence. Through proteomic + screening we have identified a novel type of kinase, tentatively named, SSK1 + (Super Signaling Kinase-1) that could connect cellular metabolism to cell + growth. Depletion of SSK1 induced cellular senescence and diminished GBM cell + growth in vitro and in a xenograft tumor model. The senescence caused by SSK1 + depletion was accompanied by the induction of p21WAF1/CIP1, a critical inducer + of cell senescence. Importantly, p21WAF1/CIP1 induction was independent of + p53, reactive oxygen species (ROS) status, and DNA damage response pathways. + Critically, the kinase activity of SSK1 is indispensable for GBM to suppress + the induction of p21WAF1/CIP1 and escape senescence. Through chemical library + screening, we identified a small molecule, which inhibited SSK1 activity in + vitro and in vivo. Treatment of SSK1 inhibitor increased p21WAF1/CIP1 and + triggered GBM senescence. Our data reveal a novel p21WAF1/CIP1 regulatory + pathway mediated by SSK1, which is essential for GBM to suppress senescence, + and suggest a novel therapy for their treatment, pharmacologically targeting + SSK1.", "venue": "", "year": 2014, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://academic.oup.com/neuro-oncology/article-pdf/16/suppl_5/v58/3597421/nou242.33.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2014-11-01", + "journal": {"volume": "16", "name": "Neuro-oncology"}, "authors": [{"authorId": + "49715313", "name": "K. Sumita"}, {"authorId": "29195749", "name": "Mindy + I. Davis"}, {"authorId": "5123505", "name": "R. Pragani"}, {"authorId": "49515406", + "name": "Jumpei Terakawa"}, {"authorId": "145457715", "name": "T. Daikoku"}, + {"authorId": "48742800", "name": "N. Majd"}, {"authorId": "145829790", "name": + "M. Shen"}, {"authorId": "4837727", "name": "Zhuyin Li"}, {"authorId": "51374815", + "name": "Xin Hu"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3275486", "name": "M. Boxer"}, {"authorId": "145183304", "name": "A. Simeonov"}, + {"authorId": "47742211", "name": "A. Sasaki"}]}, {"paperId": "ec897b66db68cd288dc4f249a2daa08fc8f03257", + "externalIds": {"MAG": "1999143583", "DOI": "10.1158/1538-7445.AM2014-NG05", + "CorpusId": 84732150}, "corpusId": 84732150, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/ec897b66db68cd288dc4f249a2daa08fc8f03257", + "title": "Abstract NG05: Depletion of a putatively druggable class of phosphatidylinositol + kinases inhibits growth of p53 null tumors", "abstract": null, "venue": "", + "year": 2014, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2014-10-01", "journal": {"volume": "74", "name": "Cancer Research"}, "authors": + [{"authorId": "5542751", "name": "B. Emerling"}, {"authorId": "50139635", + "name": "J. Hurov"}, {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": + "1401641678", "name": "R. Choo-Wing"}, {"authorId": "31554501", "name": "G. + Wulf"}, {"authorId": "13574443", "name": "Hyeseok Shim"}, {"authorId": "5493258", + "name": "K. Lamia"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "48732236", "name": "Xin Yuan"}, {"authorId": "4440909", "name": "A. Bullock"}, + {"authorId": "4772111", "name": "G. DeNicola"}, {"authorId": "5112147", "name": + "Jiaxi Song"}, {"authorId": "7505152", "name": "S. Signoretti"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "08557ebb6996dd01db41a758a2f0f8344b90ef16", + "externalIds": {"MAG": "2435209661", "CorpusId": 194485798}, "corpusId": 194485798, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/08557ebb6996dd01db41a758a2f0f8344b90ef16", + "title": "Figure 3, [A) SDS-PAGE run under non-reducing...].", "abstract": + null, "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Mathematics"], "s2FieldsOfStudy": [{"category": "Mathematics", + "source": "external"}], "publicationTypes": null, "publicationDate": "2013-05-08", + "journal": null, "authors": [{"authorId": "2435894", "name": "K. Brimacombe"}, + {"authorId": "46996935", "name": "D. Anastasiou"}, {"authorId": "6351971", + "name": "B. Hong"}, {"authorId": "5566934", "name": "W. Tempel"}, {"authorId": + "33892021", "name": "S. Dimov"}, {"authorId": "1799343", "name": "H. Veith"}, + {"authorId": "2607088", "name": "D. Auld"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig J. Thomas"}, {"authorId": + "2790262", "name": "Hee-won Park"}, {"authorId": "145829790", "name": "M. + Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3275486", + "name": "M. Boxer"}]}, {"paperId": "0cea8b880c97b38529f4f24a0745d023ff1176df", + "externalIds": {"MAG": "1980478078", "DOI": "10.1038/502181a", "CorpusId": + 4388649, "PubMed": "24108049"}, "corpusId": 4388649, "publicationVenue": {"id": + "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/0cea8b880c97b38529f4f24a0745d023ff1176df", + "title": "Metabolic syndrome: F stands for fructose and fat", "abstract": + null, "venue": "Nature", "year": 2013, "referenceCount": 10, "citationCount": + 53, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Medicine", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": ["LettersAndComments", "News"], + "publicationDate": "2013-10-10", "journal": {"volume": "502", "pages": "181-182", + "name": "Nature"}, "authors": [{"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "0ea33159c583666298a6e6c8f0081844714cc2ed", + "externalIds": {"MAG": "2030057907", "DOI": "10.1016/j.cell.2013.09.057", + "CorpusId": 17031371, "PubMed": "24209622"}, "corpusId": 17031371, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/0ea33159c583666298a6e6c8f0081844714cc2ed", + "title": "Depletion of a Putatively Druggable Class of Phosphatidylinositol + Kinases Inhibits Growth of p53-Null Tumors", "abstract": null, "venue": "Cell", + "year": 2013, "referenceCount": 42, "citationCount": 144, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867413012336/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-11-07", "journal": {"volume": + "155", "pages": "844-857", "name": "Cell"}, "authors": [{"authorId": "5542751", + "name": "B. Emerling"}, {"authorId": "50139635", "name": "J. Hurov"}, {"authorId": + "4612853", "name": "G. Poulogiannis"}, {"authorId": "8254104", "name": "Kazumi + S. Tsukazawa"}, {"authorId": "1401641678", "name": "R. Choo-Wing"}, {"authorId": + "31554501", "name": "G. Wulf"}, {"authorId": "49200178", "name": "E. Bell"}, + {"authorId": "13574443", "name": "Hyeseok Shim"}, {"authorId": "5493258", + "name": "K. Lamia"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "5679020", "name": "G. Bellinger"}, {"authorId": "47742211", "name": "A. Sasaki"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "48732236", "name": + "Xin Yuan"}, {"authorId": "4440909", "name": "A. Bullock"}, {"authorId": "4772111", + "name": "G. DeNicola"}, {"authorId": "5112147", "name": "Jiaxi Song"}, {"authorId": + "49917633", "name": "Victoria Brown"}, {"authorId": "7505152", "name": "S. + Signoretti"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "121d939e8f5f894cd9e2550e175b5afbec6978ed", "externalIds": {"MAG": "2116716449", + "DOI": "10.1158/2159-8290.CD-13-0015", "CorpusId": 7660190, "PubMed": "23715154"}, + "corpusId": 7660190, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/121d939e8f5f894cd9e2550e175b5afbec6978ed", + "title": "Metabolic and functional genomic studies identify deoxythymidylate + kinase as a target in LKB1-mutant lung cancer.", "abstract": "The LKB1/STK11 + tumor suppressor encodes a serine/threonine kinase, which coordinates cell + growth, polarity, motility, and metabolism. In non-small cell lung carcinoma, + LKB1 is somatically inactivated in 25% to 30% of cases, often concurrently + with activating KRAS mutations. Here, we used an integrative approach to define + novel therapeutic targets in KRAS-driven LKB1-mutant lung cancers. High-throughput + RNA interference screens in lung cancer cell lines from genetically engineered + mouse models driven by activated KRAS with or without coincident Lkb1 deletion + led to the identification of Dtymk, encoding deoxythymidylate kinase (DTYMK), + which catalyzes dTTP biosynthesis, as synthetically lethal with Lkb1 deficiency + in mouse and human lung cancer lines. Global metabolite profiling showed that + Lkb1-null cells had a striking decrease in multiple nucleotide metabolites + as compared with the Lkb1-wild-type cells. Thus, LKB1-mutant lung cancers + have deficits in nucleotide metabolism that confer hypersensitivity to DTYMK + inhibition, suggesting that DTYMK is a potential therapeutic target in this + aggressive subset of tumors.", "venue": "Cancer Discovery", "year": 2013, + "referenceCount": 43, "citationCount": 111, "influentialCitationCount": 2, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3753578?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-08-01", "journal": {"volume": + "3 8", "pages": "\n 870-9\n ", "name": "Cancer discovery"}, + "authors": [{"authorId": "1700568", "name": "Yan Liu"}, {"authorId": "145638995", + "name": "K. Marks"}, {"authorId": "40516027", "name": "G. Cowley"}, {"authorId": + "39474995", "name": "J. Carretero"}, {"authorId": "1933095", "name": "Qingsong + Liu"}, {"authorId": "3790196", "name": "T. J. Nieland"}, {"authorId": "46747874", + "name": "Chunxiao Xu"}, {"authorId": "9926063", "name": "Travis J Cohoon"}, + {"authorId": "144579867", "name": "P. Gao"}, {"authorId": "2144288313", "name": + "Yong Zhang"}, {"authorId": "1491946371", "name": "Zhao Chen"}, {"authorId": + "6594506", "name": "Abigail Altabef"}, {"authorId": "4557419", "name": "J. + Tchaicha"}, {"authorId": "48631933", "name": "Xiaoxu Wang"}, {"authorId": + "48918385", "name": "Sung E. Choe"}, {"authorId": "4691854", "name": "E. Driggers"}, + {"authorId": "47294251", "name": "Jianming Zhang"}, {"authorId": "12828558", + "name": "Sean T. Bailey"}, {"authorId": "3525978", "name": "N. Sharpless"}, + {"authorId": "143731085", "name": "D. Hayes"}, {"authorId": "3083071", "name": + "N. Patel"}, {"authorId": "4147848", "name": "P. Janne"}, {"authorId": "5974412", + "name": "N. Bardeesy"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": + "2339651", "name": "B. Manning"}, {"authorId": "4426388", "name": "R. Shaw"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "143905392", "name": + "R. Scully"}, {"authorId": "4668673", "name": "A. Kimmelman"}, {"authorId": + "1939017", "name": "L. Byers"}, {"authorId": "2196489", "name": "D. Gibbons"}, + {"authorId": "46528860", "name": "I. Wistuba"}, {"authorId": "2192944576", + "name": "J. Heymach"}, {"authorId": "2942901", "name": "D. Kwiatkowski"}, + {"authorId": "46392220", "name": "William Y. Kim"}, {"authorId": "145326814", + "name": "A. Kung"}, {"authorId": "3977406", "name": "N. Gray"}, {"authorId": + "3198018", "name": "D. Root"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "32596484", "name": "Kwok-Kin Wong"}]}, {"paperId": "18d974355f419c8bd42534fcdd9a1e383110f6ce", + "externalIds": {"MAG": "2033228549", "DOI": "10.1016/j.cell.2013.04.023", + "CorpusId": 7029480, "PubMed": "23663782"}, "corpusId": 7029480, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/18d974355f419c8bd42534fcdd9a1e383110f6ce", + "title": "The mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation + by Repressing SIRT4", "abstract": null, "venue": "Cell", "year": 2013, "referenceCount": + 64, "citationCount": 468, "influentialCitationCount": 37, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867413004650/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-05-09", "journal": {"volume": "153", "pages": "840-854", + "name": "Cell"}, "authors": [{"authorId": "6688912", "name": "A. Csibi"}, + {"authorId": "46775302", "name": "S. Fendt"}, {"authorId": "49672566", "name": + "Chenggang Li"}, {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": + "32210637", "name": "A. Y. Choo"}, {"authorId": "7362234", "name": "Douglas + J. Chapski"}, {"authorId": "2112433", "name": "S. Jeong"}, {"authorId": "3765048", + "name": "J. Dempsey"}, {"authorId": "3744617", "name": "A. Parkhitko"}, {"authorId": + "4644464", "name": "T. Morrison"}, {"authorId": "4397360", "name": "E. Henske"}, + {"authorId": "6212141", "name": "M. Haigis"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}, {"authorId": + "79481462", "name": "Jane J. Yu"}, {"authorId": "4037343", "name": "J. Blenis"}]}, + {"paperId": "23a08b9311d1a88ffb1b4651772f255b0e043a6d", "externalIds": {"CorpusId": + 13060080}, "corpusId": 13060080, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/23a08b9311d1a88ffb1b4651772f255b0e043a6d", + "title": "FoxO 3 coordinates metabolic pathways to maintain redox balance + in neural stem cells", "abstract": "-Ref#1 finds interesting data in the study, + is however concerned that it is entirely based on foldchanges. With the current + description of methods, s/he finds it difficult to judge the overall significance + of the data. (As an aside, cropping of blots would need to be verified by + provision of original source data). Lastly, the NAC-feeding experiments indicate + functional relevance, though they seem not to offer direct proof for the actual + molecular-mechanistic underpinnings with regard to glucose/glutamine metabolism.", + "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 18, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "4250474", + "name": "H. Yeo"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "2108446203", "name": "Yuqing Zhang"}, {"authorId": "33312849", "name": "H. + Ying"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "5056578", "name": "J. Paik"}]}, {"paperId": + "25f6ccedaeb88e88dc7f17c5f47c939b160bf533", "externalIds": {"MAG": "2104167441", + "DOI": "10.1158/2159-8290.CD-13-0063", "CorpusId": 15737239, "PubMed": "24265156"}, + "corpusId": 15737239, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/25f6ccedaeb88e88dc7f17c5f47c939b160bf533", + "title": "What a tangled web we weave: emerging resistance mechanisms to inhibition + of the phosphoinositide 3-kinase pathway.", "abstract": "UNLABELLED\nThe phosphoinositide + 3-kinase (PI3K) pathway is one of the most frequently mutated pathways in + cancer, and is actively being pursued as a therapeutic target. Despite the + importance of the PI3K pathway in cancer, durable responses to PI3K pathway-targeted + therapies are uncommon with monotherapy. Several in vitro and xenograft models + have elucidated compensatory signaling and genomic changes which may limit + the therapeutic effectiveness of PI3K inhibitors in the clinic. Future clinical + trials with prospective evaluation of tumor signaling and genomic changes + are likely to identify novel resistance mechanisms as well as subsets of patients + who may derive maximal benefit from PI3K pathway inhibitors.\n\n\nSIGNIFICANCE\nThere + are multiple ongoing clinical trials targeting the PI3K pathway members in + several malignancies. This review summarizes the known mechanisms of resistance + to targeting the PI3K pathway. Understanding of resistance mechanisms will + help to inform more rational clinical trial design to optimize the clinical + impact of targeting the PI3K pathway in cancer.", "venue": "Cancer Discovery", + "year": 2013, "referenceCount": 122, "citationCount": 132, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3864542?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "2013-12-01", "journal": {"volume": "3 12", "pages": "\n 1345-54\n ", + "name": "Cancer discovery"}, "authors": [{"authorId": "4677205", "name": "S. + Klempner"}, {"authorId": "6324437", "name": "A. Myers"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "2f1b3fa0b9ec8ba031a7269af5c488640bffe474", + "externalIds": {"MAG": "2101967659", "DOI": "10.1242/dev.091777", "CorpusId": + 8271162, "PubMed": "23715547"}, "corpusId": 8271162, "publicationVenue": {"id": + "179847ef-8e79-48e2-99ee-769211d3e729", "name": "Development", "type": "journal", + "issn": "0950-1991", "alternate_issns": ["0212-2448"], "url": "https://dev.biologists.org/", + "alternate_urls": ["http://dev.biologists.org/", "http://journals.ecs.soton.ac.uk/journals/dev.html"]}, + "url": "https://www.semanticscholar.org/paper/2f1b3fa0b9ec8ba031a7269af5c488640bffe474", + "title": "Stem cell metabolism in tissue development and aging", "abstract": + "Recent advances in metabolomics and computational analysis have deepened + our appreciation for the role of specific metabolic pathways in dictating + cell fate. Once thought to be a mere consequence of the state of a cell, metabolism + is now known to play a pivotal role in dictating whether a cell proliferates, + differentiates or remains quiescent. Here, we review recent studies of metabolism + in stem cells that have revealed a shift in the balance between glycolysis, + mitochondrial oxidative phosphorylation and oxidative stress during the maturation + of adult stem cells, and during the reprogramming of somatic cells to pluripotency. + These insights promise to inform strategies for the directed differentiation + of stem cells and to offer the potential for novel metabolic or pharmacological + therapies to enhance regeneration and the treatment of degenerative disease.", + "venue": "Development", "year": 2013, "referenceCount": 130, "citationCount": + 487, "influentialCitationCount": 39, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2013-06-15", "journal": {"volume": + "140", "pages": "2535 - 2547", "name": "Development"}, "authors": [{"authorId": + "1397529716", "name": "Ng Shyh\u2010Chang"}, {"authorId": "2028224", "name": + "G. Daley"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "390c6da813a7542e9e1b8c1d0fb200b720bf928a", "externalIds": {"MAG": "1986653575", + "DOI": "10.1074/jbc.M112.441469", "CorpusId": 205328922, "PubMed": "23640882"}, + "corpusId": 205328922, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/390c6da813a7542e9e1b8c1d0fb200b720bf928a", + "title": "Protein Tyrosine Phosphatase 1B Regulates Pyruvate Kinase M2 Tyrosine + Phosphorylation*", "abstract": "Background: Tyrosine phosphorylation of PKM2 + inhibits its activity; however, the phosphatase(s) that regulates PKM2 phosphorylation + remains unidentified. Results: PKM2 is a novel PTP1B substrate and PKM2 Tyr-105 + and Tyr-148 are key sites that mediate the interaction. Conclusion: PTP1B + regulates PKM2 tyrosine phosphorylation and activity in adipocytes. Significance: + These findings provide new insights into the regulation of adipose PKM2 activity. + Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose + homeostasis and adiposity and is a drug target for the treatment of obesity + and diabetes. Here we identify pyruvate kinase M2 (PKM2) as a novel PTP1B + substrate in adipocytes. PTP1B deficiency leads to increased PKM2 total tyrosine + and Tyr105 phosphorylation in cultured adipocytes and in vivo. Substrate trapping + and mutagenesis studies identify PKM2 Tyr-105 and Tyr-148 as key sites that + mediate PTP1B-PKM2 interaction. In addition, in vitro analyses illustrate + a direct effect of Tyr-105 phosphorylation on PKM2 activity in adipocytes. + Importantly, PTP1B pharmacological inhibition increased PKM2 Tyr-105 phosphorylation + and decreased PKM2 activity. Moreover, PKM2 Tyr-105 phosphorylation is regulated + nutritionally, decreasing in adipose tissue depots after high-fat feeding. + Further, decreased PKM2 Tyr-105 phosphorylation correlates with the development + of glucose intolerance and insulin resistance in rodents, non-human primates, + and humans. Together, these findings identify PKM2 as a novel substrate of + PTP1B and provide new insights into the regulation of adipose PKM2 activity.", + "venue": "Journal of Biological Chemistry", "year": 2013, "referenceCount": + 67, "citationCount": 46, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/288/24/17360.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-05-02", "journal": {"volume": + "288", "pages": "17360 - 17371", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "5956178", "name": "Ahmed Bettaieb"}, {"authorId": + "50186862", "name": "Jesse L Bakke"}, {"authorId": "3957054", "name": "N. + Nagata"}, {"authorId": "5647080", "name": "Kosuke Matsuo"}, {"authorId": "4692463", + "name": "Yannan Xi"}, {"authorId": "50152449", "name": "Siming Liu"}, {"authorId": + "12055558", "name": "Daniel Aboubechara"}, {"authorId": "4659311", "name": + "R. Melhem"}, {"authorId": "6126451", "name": "K. Stanhope"}, {"authorId": + "35012289", "name": "B. Cummings"}, {"authorId": "2074475036", "name": "James + Graham"}, {"authorId": "34973043", "name": "A. Bremer"}, {"authorId": "12212212", + "name": "Shu-yuan Zhang"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "29856927", "name": "Zhon-Yin Zhang"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "144769314", "name": "P. Havel"}, {"authorId": + "5546228", "name": "F. Haj"}]}, {"paperId": "44b72d6c188ee8d3a88c59bb85e55ca849bef638", + "externalIds": {"PubMedCentral": "3656466", "MAG": "2014988241", "DOI": "10.1038/nature12040", + "CorpusId": 3831884, "PubMed": "23535601"}, "corpusId": 3831884, "publicationVenue": + {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/44b72d6c188ee8d3a88c59bb85e55ca849bef638", + "title": "Glutamine supports pancreatic cancer growth through a Kras-regulated + metabolic pathway", "abstract": null, "venue": "Nature", "year": 2013, "referenceCount": + 26, "citationCount": 1418, "influentialCitationCount": 93, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3656466?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-03-01", "journal": {"volume": + "496", "pages": "101 - 105", "name": "Nature"}, "authors": [{"authorId": "38313825", + "name": "J. Son"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "33312849", "name": "H. Ying"}, {"authorId": "48631933", "name": "Xiaoxu Wang"}, + {"authorId": "50767858", "name": "S. Hua"}, {"authorId": "4968898", "name": + "M. Ligorio"}, {"authorId": "3557245", "name": "R. Perera"}, {"authorId": + "3817898", "name": "C. Ferrone"}, {"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "1397529716", "name": "Ng Shyh\u2010Chang"}, {"authorId": + "78102197", "name": "Ya''an Kang"}, {"authorId": "144926646", "name": "J. + Fleming"}, {"authorId": "5974412", "name": "N. Bardeesy"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "6212141", "name": "M. Haigis"}, {"authorId": + "5593407", "name": "R. DePinho"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4668673", "name": "A. Kimmelman"}]}, {"paperId": "4b9812d5a8d963251bfe8ad7cc6a8432672220c2", + "externalIds": {"MAG": "1976203358", "DOI": "10.1158/1538-7445.FBCR13-IA22", + "CorpusId": 83848030}, "corpusId": 83848030, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/4b9812d5a8d963251bfe8ad7cc6a8432672220c2", + "title": "Abstract IA22: PI3K and cancer metabolism", "abstract": "Phosphoinositide + 3-Kinase (PI3K) is a central enzyme in a signaling pathway that mediates cellular + responses to growth factors. The signaling pathway downstream of PI3K is highly + conserved from worms and flies to humans and genetic analysis of the pathway + has revealed a conserved role in regulating glucose metabolism and cell growth. + Mutational events that lead to hyperactivation of the PI3K pathway result + in hamartoma syndromes and cancers. Activating mutations in PIK3CA, encoding + the p110alpha catalytic subunit of PI3K or inactivating mutations in PTEN, + a phosphoinositide 3-phosphatases that reverses the effects of PI3K, are among + the most common events in solid tumors. Drugs that target PI3K are in clinical + trials for a variety of cancers. It is likely that PI3K pathway inhibitors + will need to be combined with other drugs to be broadly effective. We have + employed genetically engineered mouse models that develop cancers due to mutations + in genes in the PI3K pathway and are using these models to explore the efficacy + of PI3K pathway inhibitors as single agents or in combination with other drugs. + The role of PI3K inhibitors for treating cancers in these mouse models and + in human trials will be discussed. Citation Format: Lewis C. Cantley. PI3K + and cancer metabolism. [abstract]. In: Proceedings of the Third AACR International + Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National + Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract + nr IA22.", "venue": "", "year": 2013, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-10-01", "journal": {"volume": + "73", "name": "Cancer Research"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "4ba92ec158a39ddfe3a3c487674180ffdb2e325d", "externalIds": + {"MAG": "1480960095", "DOI": "10.1002/stem.1423", "CorpusId": 11687941, "PubMed": + "23666760"}, "corpusId": 11687941, "publicationVenue": {"id": "80635f01-c97a-4607-92eb-64f936e3cb72", + "name": "Stem Cells", "type": "journal", "alternate_names": ["Stem Cell", + "Stem cell"], "issn": "0250-6793", "alternate_issns": ["2571-7294", "1945-4570", + "1066-5099"], "url": "http://onlinelibrary.wiley.com/journal/10.1002/(issn)1549-4918", + "alternate_urls": ["http://sciencepub.net/stem/", "http://stemcells.alphamedpress.org/", + "https://onlinelibrary.wiley.com/journal/15494918"]}, "url": "https://www.semanticscholar.org/paper/4ba92ec158a39ddfe3a3c487674180ffdb2e325d", + "title": "Fetal Deficiency of Lin28 Programs Life\u2010Long Aberrations in + Growth and Glucose Metabolism", "abstract": "LIN28A/B are RNA binding proteins + implicated by genetic association studies in human growth and glucose metabolism. + Mice with ectopic over\u2010expression of Lin28a have shown related phenotypes. + Here, we describe the first comprehensive analysis of the physiologic consequences + of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b\u2010deficiency + led to dwarfism starting at different ages, and compound gene deletions showed + a cumulative dosage effect on organismal growth. Conditional gene deletion + at specific developmental stages revealed that fetal but neither neonatal + nor adult deficiency resulted in growth defects and aberrations in glucose + metabolism. Tissue\u2010specific KO mice implicated skeletal muscle\u2010deficiency + in the abnormal programming of adult growth and metabolism. The effects of + Lin28b KO could be rescued by Tsc1 haplo\u2010insufficiency in skeletal muscles. + Our data implicate fetal expression of Lin28a/b in the regulation of life\u2010long + effects on metabolism and growth, and demonstrate that fetal Lin28b acts at + least in part via mTORC1 signaling. STEM Cells 2013;31:1563\u20131573", "venue": + "Stem Cells", "year": 2013, "referenceCount": 43, "citationCount": 112, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3775935?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-08-01", "journal": {"volume": + "31", "name": "STEM CELLS"}, "authors": [{"authorId": "4293162", "name": "Gen + Shinoda"}, {"authorId": "1397529716", "name": "Ng Shyh\u2010Chang"}, {"authorId": + "8534995", "name": "T. Y. D. Soysa"}, {"authorId": "1705585", "name": "Hao + Zhu"}, {"authorId": "4531070", "name": "Marc T. Seligson"}, {"authorId": "3935506", + "name": "Samar P. Shah"}, {"authorId": "1431203868", "name": "Nora Abo-Sido"}, + {"authorId": "48326334", "name": "A. Yabuuchi"}, {"authorId": "2814984", "name": + "J. Hagan"}, {"authorId": "50193322", "name": "R. Gregory"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4642292", "name": "E. Moss"}, {"authorId": "2028224", "name": + "G. Daley"}]}, {"paperId": "4caa68d9e48032b072072dc498edea710a0ed6f8", "externalIds": + {"MAG": "2463178538", "CorpusId": 88736381}, "corpusId": 88736381, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/4caa68d9e48032b072072dc498edea710a0ed6f8", + "title": "Figure 4, Purified recombinant PKM2 was treated with either A) DMSO + or B) 1 \u03bcM ML285 followed by H2O2 for 30 minutes, diluted 100-fold and + PK activity was assayed", "abstract": null, "venue": "", "year": 2013, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Agricultural + And Food Sciences", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2013-05-08", "journal": {"volume": "", "name": ""}, "authors": + [{"authorId": "2435894", "name": "K. Brimacombe"}, {"authorId": "46996935", + "name": "D. Anastasiou"}, {"authorId": "6351971", "name": "B. Hong"}, {"authorId": + "5566934", "name": "W. Tempel"}, {"authorId": "33892021", "name": "S. Dimov"}, + {"authorId": "1799343", "name": "H. Veith"}, {"authorId": "2607088", "name": + "D. Auld"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "2148769632", "name": "Craig J. Thomas"}, {"authorId": "2790262", "name": + "Hee-won Park"}, {"authorId": "145829790", "name": "M. Shen"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3275486", "name": "M. Boxer"}]}, + {"paperId": "4e31b31649cf2547655581f8a9facfc6afdb5703", "externalIds": {"MAG": + "2748765905", "DOI": "10.1016/j.cell.2013.09.025", "CorpusId": 14504385, "PubMed": + "24120138"}, "corpusId": 14504385, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/4e31b31649cf2547655581f8a9facfc6afdb5703", + "title": "PKM2 Isoform-Specific Deletion Reveals a Differential Requirement + for Pyruvate Kinase in Tumor Cells", "abstract": null, "venue": "Cell", "year": + 2013, "referenceCount": 62, "citationCount": 417, "influentialCitationCount": + 17, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867413011628/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-10-01", "journal": {"volume": "155", "pages": "397-409", + "name": "Cell"}, "authors": [{"authorId": "5553029", "name": "W. J. Israelsen"}, + {"authorId": "40576003", "name": "T. Dayton"}, {"authorId": "34711277", "name": + "Shawn M. Davidson"}, {"authorId": "8143199", "name": "B. Fiske"}, {"authorId": + "5246254", "name": "Aaron M. Hosios"}, {"authorId": "5679020", "name": "G. + Bellinger"}, {"authorId": "1684133", "name": "J. Li"}, {"authorId": "2119040612", + "name": "Yimin Yu"}, {"authorId": "2113969237", "name": "M. Sasaki"}, {"authorId": + "40006904", "name": "J. Horner"}, {"authorId": "48793812", "name": "L. Burga"}, + {"authorId": "143740055", "name": "Jianxin Xie"}, {"authorId": "34688689", + "name": "M. Jurczak"}, {"authorId": "5593407", "name": "R. DePinho"}, {"authorId": + "3633091", "name": "C. Clish"}, {"authorId": "3196398", "name": "T. Jacks"}, + {"authorId": "5304639", "name": "R. Kibbey"}, {"authorId": "31554501", "name": + "G. Wulf"}, {"authorId": "143753942", "name": "D. D. Vizio"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "35413264", "name": "M. V. Heiden"}]}, {"paperId": "4e990a45449c113ff854ed1f56b6d786fe3de55d", + "externalIds": {"MAG": "2594708882", "DOI": "10.1038/NCB2677", "CorpusId": + 196630044}, "corpusId": 196630044, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4e990a45449c113ff854ed1f56b6d786fe3de55d", + "title": "Erratum: ERK1/2-dependent phosphorylation and nuclear translocation + of PKM2 promotes the Warburg effect (Nature Cell Biology (2012) 14 (1295-1304))", + "abstract": null, "venue": "", "year": 2013, "referenceCount": 1, "citationCount": + 8, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/ncb2677.pdf", "status": null}, "fieldsOfStudy": + ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": {"volume": "15", "name": "Nature Cell + Biology"}, "authors": [{"authorId": "143956168", "name": "Weiwei Yang"}, {"authorId": + "3169180", "name": "Yanhua Zheng"}, {"authorId": "143733371", "name": "Yan + Xia"}, {"authorId": "2579875", "name": "Haitao Ji"}, {"authorId": "48283607", + "name": "Xiaomin Chen"}, {"authorId": "152831013", "name": "F. Guo"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "50138848", "name": "K. Aldape"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5467266", "name": + "Zhimin Lu"}]}, {"paperId": "52b3d03716946f615947f2f6b5190d9e37aaa689", "externalIds": + {"MAG": "2474673362", "CorpusId": 184097184}, "corpusId": 184097184, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/52b3d03716946f615947f2f6b5190d9e37aaa689", + "title": "Figure 5, [A) ML285 shows a dose-response...].", "abstract": null, + "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Mathematics"], + "s2FieldsOfStudy": [{"category": "Mathematics", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2013-05-08", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "2435894", "name": "K. Brimacombe"}, {"authorId": "46996935", "name": "D. + Anastasiou"}, {"authorId": "6351971", "name": "B. Hong"}, {"authorId": "5566934", + "name": "W. Tempel"}, {"authorId": "33892021", "name": "S. Dimov"}, {"authorId": + "1799343", "name": "H. Veith"}, {"authorId": "2607088", "name": "D. Auld"}, + {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "2148769632", + "name": "Craig J. Thomas"}, {"authorId": "2790262", "name": "Hee-won Park"}, + {"authorId": "145829790", "name": "M. Shen"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "3275486", "name": "M. Boxer"}]}, {"paperId": + "566c23aacfd9e4dea5475f5c69bba67368eef165", "externalIds": {"MAG": "2461999919", + "CorpusId": 89186503}, "corpusId": 89186503, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/566c23aacfd9e4dea5475f5c69bba67368eef165", + "title": "Figure 8, [A) Intracellular ROS levels measured...].", "abstract": + null, "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-05-08", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2435894", "name": "K. Brimacombe"}, + {"authorId": "46996935", "name": "D. Anastasiou"}, {"authorId": "6351971", + "name": "B. Hong"}, {"authorId": "5566934", "name": "W. Tempel"}, {"authorId": + "33892021", "name": "S. Dimov"}, {"authorId": "1799343", "name": "H. Veith"}, + {"authorId": "2607088", "name": "D. Auld"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig J. Thomas"}, {"authorId": + "2790262", "name": "Hee-won Park"}, {"authorId": "145829790", "name": "M. + Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3275486", + "name": "M. Boxer"}]}, {"paperId": "5f119735ec5878e6bd483b8944f6e416cbafa1e0", + "externalIds": {"MAG": "2489732030", "CorpusId": 100351651}, "corpusId": 100351651, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/5f119735ec5878e6bd483b8944f6e416cbafa1e0", + "title": "Figure 7, [A) [1-14C]glucose flux through PPP...].", "abstract": + null, "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}], "publicationTypes": null, "publicationDate": "2013-05-08", + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "2435894", + "name": "K. Brimacombe"}, {"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "6351971", "name": "B. Hong"}, {"authorId": "5566934", "name": + "W. Tempel"}, {"authorId": "33892021", "name": "S. Dimov"}, {"authorId": "1799343", + "name": "H. Veith"}, {"authorId": "2607088", "name": "D. Auld"}, {"authorId": + "35413264", "name": "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig + J. Thomas"}, {"authorId": "2790262", "name": "Hee-won Park"}, {"authorId": + "145829790", "name": "M. Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3275486", "name": "M. Boxer"}]}, {"paperId": "67c00ce4d2e48ee6fddb2fafafbb50a3c5f0bdd7", + "externalIds": {"MAG": "2967664220", "DOI": "10.1200/JCO.2013.31.15_SUPPL.5521", + "CorpusId": 201980568}, "corpusId": 201980568, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/67c00ce4d2e48ee6fddb2fafafbb50a3c5f0bdd7", + "title": "PTEN loss as a context-dependent determinant of patient outcomes + in obese and non-obese endometrioid endometrial cancer patients.", "abstract": + "5521 Background: Aberrations in the PI3K pathway, the central relay pathway + of insulin signals, occur in the majority of endometrioid endometrial cancers. + We explored the prognostic utility of PIK3...", "venue": "", "year": 2013, + "referenceCount": 0, "citationCount": 2, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Medicine", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-05-20", "journal": {"volume": + "31", "pages": "5521-5521", "name": "Journal of Clinical Oncology"}, "authors": + [{"authorId": "152983291", "name": "Z. Ju"}, {"authorId": "2974900", "name": + "S. Westin"}, {"authorId": "6416382", "name": "R. Broaddus"}, {"authorId": + "2149869719", "name": "Jie Li"}, {"authorId": "35508831", "name": "N. Pal"}, + {"authorId": "8500699", "name": "K. Lu"}, {"authorId": "3124983", "name": + "R. Coleman"}, {"authorId": "4677205", "name": "S. Klempner"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2241330", "name": "G. Mills"}, + {"authorId": "6324437", "name": "A. Myers"}]}, {"paperId": "6d97c83fb5028df949a618c2c3cb269d97cdc7fc", + "externalIds": {"MAG": "2152951302", "DOI": "10.1016/j.cell.2013.09.059", + "CorpusId": 18616833, "PubMed": "24209617"}, "corpusId": 18616833, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/6d97c83fb5028df949a618c2c3cb269d97cdc7fc", + "title": "Lin28 Enhances Tissue Repair by Reprogramming Cellular Metabolism", + "abstract": null, "venue": "Cell", "year": 2013, "referenceCount": 86, "citationCount": + 286, "influentialCitationCount": 20, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867413012786/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-11-07", "journal": {"volume": "155", "pages": "778-792", + "name": "Cell"}, "authors": [{"authorId": "1397529716", "name": "Ng Shyh\u2010Chang"}, + {"authorId": "1705585", "name": "Hao Zhu"}, {"authorId": "8534995", "name": + "T. Y. D. Soysa"}, {"authorId": "4293162", "name": "Gen Shinoda"}, {"authorId": + "4531070", "name": "Marc T. Seligson"}, {"authorId": "7684299", "name": "Kaloyan + M Tsanov"}, {"authorId": "3747859", "name": "Liem H. Nguyen"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2028224", "name": "G. Daley"}]}, {"paperId": "706d1252316288db46ed1f0322c1c76519f15a98", + "externalIds": {"MAG": "2518362649", "DOI": "10.1182/BLOOD.V122.21.793.793", + "CorpusId": 89162777}, "corpusId": 89162777, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/706d1252316288db46ed1f0322c1c76519f15a98", + "title": "Differential Dependence On Aerobic Glycolysis In Normal and Malignant + Hematopoietic Stem and Progenitor Cells To Sustain Daughter Cell Production", + "abstract": "How glucose is metabolized can influence cell function, but whether + differences in glucose metabolism reflect, or dictate, cell state is not clear + and is of particular interest given the association of cancer with aerobic + glycolysis. Studies on cancer cell lines have indicated that increased glucose + uptake with lactate production regardless of oxygen concentration, a phenomenon + also known as the Warburg effect, is promoted in part by expression of the + M2 isoform of pyruvate kinase (PKM2) and the muscle form of lactate dehydrogenase + A (LDHA). Normal somatic cells thought to also preferentially use glycolytic + metabolism are tissue stem cells, particularly the self-renewing hematopoietic + stem cells (HSC) resident in the hypoxic microenvironment of the bone marrow. + It remains to be defined, however whether proliferating hematopoietic progenitor + cells rely on aerobic glycolysis and whether malignant and normal hematopoietic + cells are dependent on the same metabolic regulation. We observed that PKM2 + and LDHA are the predominant isoforms expressed by all BM hematopoietic cells. + To further understand the role of glycolytic metabolism in hematopoiesis and + hematological malignancy, we utilized a mouse strain that allows conditional + deletion of the PKM2 specific exon 10. Deletion of PKM2 in hematopoetic cells + leads to expression of PKM1, accompanied with partial inhibition of lactate + production and decreased glycolytic intermediates in the hematopoietic stem/progenitor + cell (HSPC) population. Loss of PKM2 compromises the long-term repopulation + capacity of HSPCs as revealed by serial transplantation assay. Interestingly, + the repopulating defects resulting from PKM2 depletion appear to involve progenitors, + perhaps due to inadequate biomass generation necessary for robust cell proliferation. + To confirm that the effect of PKM2 deletion on HSPC function is due to metabolic + changes rather than other putative PKM2 functions, we engineered a mouse strain + that allowed conditional knockout of LDHA to more potently impair aerobic + glycolysis. LDHA deletion completely inhibited lactate production, enhanced + ROS levels in hematopoietic cells and impaired long-term BM repopulating activity. + In contrast to PKM2 deletion that affects progenitor but not stem cells, LDHA + depletion impacts both stem cell maintenance and progenitor cell proliferation. + Deletion of either PKM2 or LDHA markedly suppressed leukemia initiation by + either putative stem cell (BCR-ABL) or progenitor (MLL-AF9) transforming alleles. + Therefore, modulating aeroblic glycolysis has effects on normal hematopoietic + cells that depend upon cell state and negatively impacts leukemic growth regardless + of cell state. The differential sensitivity of normal and malignant cells + to modulation of aerobic glycolysis suggests a potential therapeutic opportunity + for leukemia intervention. Disclosures: No relevant conflicts of interest + to declare.", "venue": "", "year": 2013, "referenceCount": 0, "citationCount": + 3, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-11-15", "journal": {"volume": + "122", "pages": "793-793", "name": "Blood"}, "authors": [{"authorId": "47906491", + "name": "Ying-hua Wang"}, {"authorId": "5553029", "name": "W. J. Israelsen"}, + {"authorId": "47381858", "name": "Dongjun Lee"}, {"authorId": "34345448", + "name": "V. Yu"}, {"authorId": "5100030", "name": "N. T. Jeanson"}, {"authorId": + "3633091", "name": "C. Clish"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "5002337", + "name": "D. Scadden"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '252947' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:42 GMT + Via: + - 1.1 c1474fffdbf1131e0074a750a326b7b4.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - 0SMBEnsk7rmup74lOcJchCKh3hfLcuiTO3gQa4lfq9_Ot618kBnuJQ== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOaTEDAvHcFgmw= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '252947' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:42 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - e5c47029-3a2b-499a-9caf-0cd721772e5f + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=300&limit=100 + response: + body: + string: '{"offset": 300, "next": 400, "data": [{"paperId": "8255336c9ed629fca92835b1ea89e4c396089b7c", + "externalIds": {"MAG": "2335585954", "DOI": "10.1158/1538-7445.AM2013-4265", + "CorpusId": 75158058}, "corpusId": 75158058, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/8255336c9ed629fca92835b1ea89e4c396089b7c", + "title": "Abstract 4265: Derivation and characterization of endometrial cancer + cells resistant to phosphatidylinositol-3-kinase (PI3K) pathway inhibitors.", + "abstract": "Endometrial cancer remains the most common gynecologic malignancy + in the United States with an estimated 43,000 cases annually. Limited options + exist for patients with recurrent endometrial cancer after tumor progression + following platinum/taxane combinations, and newer therapies are needed. Endometrial + cancers have among the highest rates of oncogenic aberrations in the phosphatidylinositol-3-kinase + (PI3K) pathway with frequencies approaching 75%, and clinical trials targeting + components on the PI3K pathway are ongoing. Despite the clinical observation + that many responses to PI3K inhibitors are short lived an understanding of + the molecular mechanisms of resistance is lacking. We have derived endometrial + cancer cell lines resistant to a panel of PI3K/AKT/mTOR inhibitors in clinical + development in an effort to understand molecular mechanisms and signaling + changes underlying resistance to PI3K-targeted therapy. All lines have previously + undergone mutational analysis of the PI3K and RAS-ERK pathways. Representative + compounds inhibiting each node in the canonical class I PI3K signaling cascade + have been chosen. These agents have been synthesized base on the published + structures and include a pan-p110 inhibitor, an allosteric AKT inhibitor, + a dual p110-mTOR, and a MEK inhibitor. Using parallel high-throughput intracellular + phospho-kinase and phospho-receptor tyrosine kinase (RTK) arrays for screening + we have identified candidate common resistance mechanisms to inhibition of + signaling nodes in the PI3K pathway. The phospho-screening approach has highlighted + the interplay between PI3K/AKT/mTOR signaling and the Ras/Raf/MEK/ERK pathways + in the development of resistance. We have begun to validate ERK upregulation + as an activated escape pathway in patient samples from an AKT inhibitor clinical + trial. Conserved resistance profiles may ultimately be used to define a subset + of endometrial cancer patients unlikely to respond to PI3K/Akt/mTOR inhibitors + and may inform more rational early phase combination strategies. Citation + Format: Samuel J. Klempner, Andrea P. Myers, Jane Li, Gordon Mills, Lewis + C. Cantley. Derivation and characterization of endometrial cancer cells resistant + to phosphatidylinositol-3-kinase (PI3K) pathway inhibitors. [abstract]. In: + Proceedings of the 104th Annual Meeting of the American Association for Cancer + Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res + 2013;73(8 Suppl):Abstract nr 4265. doi:10.1158/1538-7445.AM2013-4265", "venue": + "", "year": 2013, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-04-15", "journal": {"volume": + "73", "pages": "4265-4265", "name": "Cancer Research"}, "authors": [{"authorId": + "4677205", "name": "S. Klempner"}, {"authorId": "6324437", "name": "A. Myers"}, + {"authorId": "2108996618", "name": "Jane Li"}, {"authorId": "2241330", "name": + "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "8f539806f7b279e93e7f415f1ac7b9d4c4e855f4", "externalIds": {"MAG": "2604158347", + "DOI": "10.1200/JCO.2013.31.15_SUPPL.5524", "CorpusId": 79293091}, "corpusId": + 79293091, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/8f539806f7b279e93e7f415f1ac7b9d4c4e855f4", + "title": "Phase II, two-stage, two-arm, PIK3CA mutation stratified trial of + MK-2206 in recurrent endometrial cancer (EC).", "abstract": "5524 Background: + EC has high rates of PI3K pathway alteration including PTEN mutation (50%) + or IHC loss (>50%), PIK3CA mutation (25-40%) and PIK3R1 (20%) mutation. MK-2206 + is an allosteric inhibitor of AKT, an effector kinase of PI3K signals. We + hypothesized that pts whose tumors harbored PIK3CA mutations would be more + likely to benefit from MK-2206 than those without PIK3CA mutation. Methods: + Pts had recurrent or advanced EC; all histologies except MMMT were eligible. + Up to 2 prior chemo lines were permitted; excluding prior treatment with PI3K/MTOR + inhibitors. The first 19 pts were treated with MK-2206 200mg QW; due to initial + skin toxicity rates, the starting dose was amended to 135mg QW. Co-primary + endpoints were objective response and 6 mo PFS. The first 37 pts were stratified + retrospectively. PIK3CA MT included R88Q, K111N, E110K, E418K, C420R, E453K, + E542K/V,E545K, Q546R, H701P, M1043V, H1047R/L/Y changes. Independent Simon + 2-stage tests were planned within PIK3CA MT and WT stratum: for MT, n1=15 + a...", "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 22, + "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-05-20", "journal": {"volume": + "31", "pages": "5524-5524", "name": "Journal of Clinical Oncology"}, "authors": + [{"authorId": "6324437", "name": "A. Myers"}, {"authorId": "6416382", "name": + "R. Broaddus"}, {"authorId": "3553012", "name": "V. Makker"}, {"authorId": + "49610180", "name": "P. Konstantinopoulos"}, {"authorId": "5340828", "name": + "R. Drapkin"}, {"authorId": "8523393", "name": "N. Horowitz"}, {"authorId": + "2108419806", "name": "Joyce F. Liu"}, {"authorId": "8315735", "name": "P. + Hummelen"}, {"authorId": "1397965147", "name": "F. Meric-Bernstam"}, {"authorId": + "2167106", "name": "M. Birrer"}, {"authorId": "39667616", "name": "L. Doyle"}, + {"authorId": "3124983", "name": "R. Coleman"}, {"authorId": "6128162", "name": + "C. Aghajanian"}, {"authorId": "2241330", "name": "G. Mills"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6927295", "name": "U. Matulonis"}, + {"authorId": "2974900", "name": "S. Westin"}]}, {"paperId": "97c4153b36f88514088843ecf246fbe88f520443", + "externalIds": {"MAG": "2781795124", "DOI": "10.1038/nature12317", "CorpusId": + 4427426}, "corpusId": 4427426, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/97c4153b36f88514088843ecf246fbe88f520443", + "title": "Corrigendum: Glutamine supports pancreatic cancer growth through + a KRAS-regulated metabolic pathway", "abstract": null, "venue": "Nature", + "year": 2013, "referenceCount": 1, "citationCount": 7, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/nature12317.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-07-01", "journal": {"volume": + "499", "pages": "504-504", "name": "Nature"}, "authors": [{"authorId": "38313825", + "name": "J. Son"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "33312849", "name": "H. Ying"}, {"authorId": "48631933", "name": "Xiaoxu Wang"}, + {"authorId": "50767858", "name": "S. Hua"}, {"authorId": "4968898", "name": + "M. Ligorio"}, {"authorId": "3557245", "name": "R. Perera"}, {"authorId": + "3817898", "name": "C. Ferrone"}, {"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "1397529716", "name": "Ng Shyh\u2010Chang"}, {"authorId": + "78102197", "name": "Ya''an Kang"}, {"authorId": "144926646", "name": "J. + Fleming"}, {"authorId": "5974412", "name": "N. Bardeesy"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "6212141", "name": "M. Haigis"}, {"authorId": + "5593407", "name": "R. DePinho"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4668673", "name": "A. Kimmelman"}]}, {"paperId": "9b04e9c9a086f25693ebbf5b4ae487198d2c39ae", + "externalIds": {"MAG": "2473337304", "CorpusId": 88594529}, "corpusId": 88594529, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9b04e9c9a086f25693ebbf5b4ae487198d2c39ae", + "title": "Figure 6, ML285-bound crystal structure of human pyruvate kinase + M2 (PDB code: 3GR4)", "abstract": null, "venue": "", "year": 2013, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Computer Science", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2013-05-08", + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "2435894", + "name": "K. Brimacombe"}, {"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "6351971", "name": "B. Hong"}, {"authorId": "5566934", "name": + "W. Tempel"}, {"authorId": "33892021", "name": "S. Dimov"}, {"authorId": "1799343", + "name": "H. Veith"}, {"authorId": "2607088", "name": "D. Auld"}, {"authorId": + "35413264", "name": "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig + J. Thomas"}, {"authorId": "2790262", "name": "Hee-won Park"}, {"authorId": + "145829790", "name": "M. Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3275486", "name": "M. Boxer"}]}, {"paperId": "9ca3c60e4f1b3cfe804d13452eb4bb17b04ed2f1", + "externalIds": {"PubMedCentral": "3737294", "MAG": "2003997444", "DOI": "10.4161/cc.25307", + "CorpusId": 9104182, "PubMed": "23759579"}, "corpusId": 9104182, "publicationVenue": + {"id": "1bce1796-d800-4a09-91e5-d3e3ed025037", "name": "Cell Cycle", "type": + "journal", "issn": "1551-4005", "url": "http://www.landesbioscience.com/journals/cc/", + "alternate_urls": ["http://www.tandfonline.com/loi/kccy20"]}, "url": "https://www.semanticscholar.org/paper/9ca3c60e4f1b3cfe804d13452eb4bb17b04ed2f1", + "title": "Pancreatic cancers rely on a novel glutamine metabolism pathway + to maintain redox balance", "abstract": "In order for a cell to dupli-cate, + it must double its genome, protein content and lipid mass. This process requires + energy in the form of ATP and NADPH. However, unlike ATP, the amount of NADPH + required for biosyn-thesis is much greater than that needed for homeostasis, + which makes the genera-tion of NADPH rate limiting for cellular proliferation. + NADPH is used for both macromolecular biosynthesis (e.g., lipids and deoxynucleotide + triphosphates) and the maintenance of a reduced intracellular environment.", + "venue": "Cell Cycle", "year": 2013, "referenceCount": 10, "citationCount": + 71, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.tandfonline.com/doi/pdf/10.4161/cc.25307?needAccess=true", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Editorial"], "publicationDate": "2013-06-10", "journal": {"volume": "12", + "pages": "1987 - 1988", "name": "Cell Cycle"}, "authors": [{"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "38313825", "name": "J. Son"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4668673", "name": "A. Kimmelman"}]}, + {"paperId": "9ec45094433c316627a794899609c5ea23924c68", "externalIds": {"MAG": + "2056633943", "DOI": "10.1038/nrc3483", "CorpusId": 42960121, "PubMed": "23446547"}, + "corpusId": 42960121, "publicationVenue": {"id": "db36cc4c-07df-41a8-9169-9ace7e520923", + "name": "Nature Reviews. Cancer", "type": "journal", "alternate_names": ["Nature + Reviews Cancer", "Nat Rev Cancer"], "issn": "1474-175X", "url": "https://www.nature.com/nrc/", + "alternate_urls": ["http://www.nature.com/nrc/index.html"]}, "url": "https://www.semanticscholar.org/paper/9ec45094433c316627a794899609c5ea23924c68", + "title": "Cancer metabolism: fatty acid oxidation in the limelight", "abstract": + null, "venue": "Nature Reviews. Cancer", "year": 2013, "referenceCount": 45, + "citationCount": 838, "influentialCitationCount": 52, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3766957?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review"], "publicationDate": "2013-04-01", "journal": {"volume": "13", "pages": + "227-232", "name": "Nature Reviews Cancer"}, "authors": [{"authorId": "6988610", + "name": "A. Carracedo"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4499580", "name": "P. Pandolfi"}]}, {"paperId": "9ed2501454dca0cb728165c439b300fcab7e2793", + "externalIds": {"MAG": "2108516575", "DOI": "10.1038/nm.3175", "CorpusId": + 3029955, "PubMed": "23584089"}, "corpusId": 3029955, "publicationVenue": {"id": + "9e995b6d-f30b-4ab4-a13b-3dc2cc992f47", "name": "Nature Network Boston", "type": + "journal", "alternate_names": ["Nat Netw Boston", "Nat Med", "Nature Medicine"], + "issn": "1744-7933", "alternate_issns": ["1078-8956"], "url": "https://www.nature.com/nature/articles?code=archive_news", + "alternate_urls": ["http://www.nature.com/news", "http://www.nature.com/nm/", + "http://www.nature.com/nm/index.html"]}, "url": "https://www.semanticscholar.org/paper/9ed2501454dca0cb728165c439b300fcab7e2793", + "title": "A colorectal cancer classification system that associates cellular + phenotype and responses to therapy", "abstract": null, "venue": "Nature Network + Boston", "year": 2013, "referenceCount": 38, "citationCount": 834, "influentialCitationCount": + 36, "isOpenAccess": true, "openAccessPdf": {"url": "https://infoscience.epfl.ch/record/195200/files/Sadanandam-NMed2013CRC_subtypes.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-05-01", "journal": {"volume": "19", "pages": "619-625", + "name": "Nature Medicine"}, "authors": [{"authorId": "49973308", "name": "A. + Sadanandam"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "145819509", "name": "K. Homicsko"}, {"authorId": "20991761", "name": "E. + Collisson"}, {"authorId": "47487491", "name": "W. J. Gibb"}, {"authorId": + "38356613", "name": "S. Wullschleger"}, {"authorId": "3495449", "name": "L. + Ostos"}, {"authorId": "4425076", "name": "William A. Lannon"}, {"authorId": + "3770955", "name": "C. Grotzinger"}, {"authorId": "36628429", "name": "M. + D. Rio"}, {"authorId": "3757419", "name": "B. Lhermitte"}, {"authorId": "2923001", + "name": "A. Olshen"}, {"authorId": "4406446", "name": "B. Wiedenmann"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144146923", "name": "J. Gray"}, + {"authorId": "6883889", "name": "D. Hanahan"}]}, {"paperId": "a38bbd62da8f6c20e8dd61cc57855bc2c64827a0", + "externalIds": {"MAG": "1977846137", "DOI": "10.1016/j.cell.2013.06.026", + "CorpusId": 3012263, "PubMed": "23830207"}, "corpusId": 3012263, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/a38bbd62da8f6c20e8dd61cc57855bc2c64827a0", + "title": "MicroRNA-Antagonism Regulates Breast Cancer Stemness and Metastasis + via TET-Family-Dependent Chromatin Remodeling", "abstract": null, "venue": + "Cell", "year": 2013, "referenceCount": 81, "citationCount": 418, "influentialCitationCount": + 20, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867413007654/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-07-18", "journal": {"volume": + "154", "pages": "311-324", "name": "Cell"}, "authors": [{"authorId": "9673009", + "name": "S. Song"}, {"authorId": "6739662", "name": "L. Poliseno"}, {"authorId": + "2967391", "name": "M. Song"}, {"authorId": "2901501", "name": "U. Ala"}, + {"authorId": "4817196", "name": "Kaitlyn A. Webster"}, {"authorId": "6294709", + "name": "Christopher Ng"}, {"authorId": "48084982", "name": "Gary Beringer"}, + {"authorId": "7593991", "name": "Nicolai J. Brikbak"}, {"authorId": "48732236", + "name": "Xin Yuan"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "145960454", "name": "A. Richardson"}, {"authorId": "4499580", "name": "P. + Pandolfi"}]}, {"paperId": "a8699a6f8c73acfcd0ce50c95c2ac0e5c53fea3f", "externalIds": + {"MAG": "2004768888", "DOI": "10.1016/j.molcel.2012.10.003", "CorpusId": 40564326, + "PubMed": "23142078"}, "corpusId": 40564326, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/a8699a6f8c73acfcd0ce50c95c2ac0e5c53fea3f", + "title": "Metabolic stress controls mTORC1 lysosomal localization and dimerization + by regulating the TTT-RUVBL1/2 complex.", "abstract": null, "venue": "Molecules + and Cells", "year": 2013, "referenceCount": 44, "citationCount": 172, "influentialCitationCount": + 14, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276512008556/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-01-10", "journal": {"volume": + "49 1", "pages": "\n 172-85\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "46876889", "name": "Sang Gyun Kim"}, {"authorId": + "34846304", "name": "G. Hoffman"}, {"authorId": "4612853", "name": "G. Poulogiannis"}, + {"authorId": "8191429", "name": "G. Buel"}, {"authorId": "6603165", "name": + "Y. Jang"}, {"authorId": "120343663", "name": "Ki-Won Lee"}, {"authorId": + "122904929", "name": "Bo-Yeon Kim"}, {"authorId": "6286526", "name": "R. Erikson"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "32210637", "name": + "A. Y. Choo"}, {"authorId": "4037343", "name": "J. Blenis"}]}, {"paperId": + "abe8378269942bdeb1e9db00e524a52ca3da7826", "externalIds": {"MAG": "2038733728", + "DOI": "10.1016/j.molcel.2013.08.044", "CorpusId": 28476909, "PubMed": "24095280"}, + "corpusId": 28476909, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/abe8378269942bdeb1e9db00e524a52ca3da7826", + "title": "Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and + cell proliferation.", "abstract": null, "venue": "Molecules and Cells", "year": + 2013, "referenceCount": 48, "citationCount": 118, "influentialCitationCount": + 8, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276513006448/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-10-24", "journal": {"volume": "52 2", "pages": "\n 161-72\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "83946576", "name": "Che-Hung + Shen"}, {"authorId": "22261570", "name": "P. Yuan"}, {"authorId": "1398525526", + "name": "R. P\u00e9rez-Lorenzo"}, {"authorId": "1591129979", "name": "Yaqing + Zhang"}, {"authorId": "2108098779", "name": "S. Lee"}, {"authorId": "2057924812", + "name": "Yang Ou"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "143918840", "name": "B. Zheng"}]}, + {"paperId": "ac3f02f8915a3060710dfacddef49cd04aaa58a6", "externalIds": {"MAG": + "2003605385", "PubMedCentral": "3681899", "DOI": "10.1038/nbt.2530", "CorpusId": + 5596677, "PubMed": "23604282"}, "corpusId": 5596677, "publicationVenue": {"id": + "458166b3-de17-4bf3-bbbb-e53782de2f0f", "name": "Nature Biotechnology", "type": + "journal", "alternate_names": ["Nat Biotechnol"], "issn": "1087-0156", "url": + "http://www.nature.com/nbt/", "alternate_urls": ["http://www.nature.com/nbt"]}, + "url": "https://www.semanticscholar.org/paper/ac3f02f8915a3060710dfacddef49cd04aaa58a6", + "title": "Heterogeneity of tumor-induced gene expression changes in the human + metabolic network", "abstract": null, "venue": "Nature Biotechnology", "year": + 2013, "referenceCount": 103, "citationCount": 337, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/nbt.2530.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-04-01", "journal": {"volume": + "31", "pages": "522 - 529", "name": "Nature biotechnology"}, "authors": [{"authorId": + "2112348570", "name": "Jie Hu"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "6261511", "name": "J. Bielas"}, {"authorId": "1395754331", "name": + "J. O\u2019Sullivan"}, {"authorId": "5833598", "name": "K. Sheahan"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3804233", "name": "M. V. Vander + Heiden"}, {"authorId": "2482068", "name": "D. Vitkup"}]}, {"paperId": "adcf5a6db1587a5b59458f4a3e2fea40bc2050c0", + "externalIds": {"MAG": "2287011628", "DOI": "10.1017/CBO9781139046947.019", + "CorpusId": 87836834}, "corpusId": 87836834, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/adcf5a6db1587a5b59458f4a3e2fea40bc2050c0", + "title": "Molecular Oncology: PI3K", "abstract": null, "venue": "", "year": + 2013, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": null, "authors": [{"authorId": "13782167", "name": "K. Courtney"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "b04099c383dd23ad783575454d0cbd1772d37b8c", + "externalIds": {"MAG": "2160689051", "DOI": "10.1158/1078-0432.CCR-13-2570", + "CorpusId": 416252, "PubMed": "24166909"}, "corpusId": 416252, "publicationVenue": + {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", "name": "Clinical Cancer Research", + "type": "journal", "alternate_names": ["Clin Cancer Res"], "issn": "1078-0432", + "url": "https://clincancerres.aacrjournals.org/", "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/b04099c383dd23ad783575454d0cbd1772d37b8c", + "title": "Targeting Metabolic Scavenging in Pancreatic Cancer", "abstract": + "Pancreatic tumor metabolism is rewired to facilitate survival and growth + in a nutrient-depleted environment. This leads to a unique dependence on metabolic + recycling and scavenging pathways, including NAD salvage. Targeting this pathway + in pancreatic cancer disrupts metabolic homeostasis and impairs tumor growth. + Clin Cancer Res; 20(1); 6\u20138. \u00a92013 AACR.", "venue": "Clinical Cancer + Research", "year": 2013, "referenceCount": 14, "citationCount": 6, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3930347?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["LettersAndComments", + "JournalArticle"], "publicationDate": "2013-10-28", "journal": {"volume": + "20", "pages": "6 - 8", "name": "Clinical Cancer Research"}, "authors": [{"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "b4d4419ca3548e0b605db76e9a91a4b8d5a9740b", "externalIds": {"MAG": + "2946633963", "DOI": "10.1158/1538-7445.FBCR13-C60", "CorpusId": 83941491}, + "corpusId": 83941491, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/b4d4419ca3548e0b605db76e9a91a4b8d5a9740b", + "title": "Abstract C60: Vitamin C inhibits the survival and growth of colorectal + cancer cells with KRAS or BRAF mutations", "abstract": "Although more than + half of colorectal cancer patients have either KRAS or BRAF mutations, targeted + therapies for these subgroups of cancer patients are lacking. We previously + showed that isogenic human colorectal cancer cell (CRC) lines harboring a + KRAS or BRAF mutation up-regulate the expression of glucose transporter 1 + (GLUT1), and increase glucose uptake and glycolysis. In this study, we go + on to show that KRAS or BRAF mutant cells exhibit a significant increase in + the uptake of vitamin C, mainly in its oxidized form, dehydroascorbic acid + (DHA), relative to their wild-type counterparts through GLUT1. Notably, CRCs + did not uptake vitamin C in its reduced form, possibly due to the fact that + its known transporters, sodium vitamin C cotransporters (SVCTs) were generally + not present in CRCs. Deletion of GLUT1 in mutant cells, overexpression of + GLUT1 in wild-type cells and competition assays between glucose and DHA confirmed + that GLUT1 is both necessary and sufficient for the uptake of vitamin C in + CRCs. Both mutant and wild-type cells were able to grow in low glucose (1-2 + mM) at a similar rate. In the same condition, we found vitamin C to be selectively + toxic to KRAS and BRAF mutant cells, causing them to undergo apoptosis. In + contrast, in high glucose levels (>10 mM), a similar concentration of vitamin + C had no effect on the survival and growth of mutant cells. In addition, vitamin + C significantly inhibited the growth of cancer cells with KRAS or BRAF mutations + in vivo xenografts models. To find the mechanism by which vitamin C induces + cell death in KRAS or BRAF mutant cells, we performed targeted metabolomics + using LC/MS. Both unlabeled total metabolite analysis and flux analysis with + C13-Glucose isotope strongly suggested that vitamin C re-routes glucose usage + from aerobic glycolysis and non-oxidative pentose phosphate pathway (PPP) + to the oxidative PPP to compensate for the lower levels of NADPH which was + rapidly consumed to reduce GSSH to GSH. Having taken up exclusively DHA, the + oxidized state of vitamin C, the mutant cells immediately use GSH to reduce + Vitamin C, resulting in the accumulation of GSSH. Shunting glucose to the + oxidative PPP reduces aerobic glycolysis, lowering ATP levels, and decreases + glucose anabolism, disfavoring the synthesis of nucleic acids, lipid and amino + acids, all needed for the survival and growth of mutant cells. Surprisingly + the level of reactive oxidative stress (ROS) was largely unchanged following + vitamin C treatment possibly because increased levels of vitamin C served + as an anti-oxidant in mutant cells. There are currently more than three clinical + trials phase I/II examining the effect of high dose vitamin C via intravenous + administration in patients against lymphoma or solid cancers including CRCs. + Our findings will provide proof of concept that KRAS or BRAF mutations in + CRC can be predictive biomarkers for vitamin C therapy. Citation Format: Jihye + Yun, Adam Kavalier, Jatin Roper, Steve Gross, Carlo Rago, Nickolas Papadopoulos, + Bert Vogelstein, Lewis Cantley. Vitamin C inhibits the survival and growth + of colorectal cancer cells with KRAS or BRAF mutations. [abstract]. In: Proceedings + of the Third AACR International Conference on Frontiers in Basic Cancer Research; + Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res + 2013;73(19 Suppl):Abstract nr C60.", "venue": "", "year": 2013, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2013-10-01", "journal": {"volume": "73", "name": + "Cancer Research"}, "authors": [{"authorId": "40164091", "name": "Jihye Yun"}, + {"authorId": "8391227", "name": "A. Kavalier"}, {"authorId": "145864068", + "name": "J. Roper"}, {"authorId": "5769141", "name": "S. Gross"}, {"authorId": + "1907762", "name": "C. Rago"}, {"authorId": "144798543", "name": "N. Papadopoulos"}, + {"authorId": "1965563", "name": "B. Vogelstein"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "b592c88fb95851c920810c0cb00b3a497eab2d4a", + "externalIds": {"MAG": "1966414227", "DOI": "10.1126/scisignal.2003936", "CorpusId": + 206671943, "PubMed": "23716717"}, "corpusId": 206671943, "publicationVenue": + {"id": "c0efe552-8a0a-41a7-8ce2-340fb0dbfe6f", "name": "Science Signaling", + "type": "journal", "alternate_names": ["Sci Signal"], "issn": "1945-0877", + "url": "https://www.sciencemag.org/", "alternate_urls": ["https://stke.sciencemag.org/about/", + "https://stke.sciencemag.org/"]}, "url": "https://www.semanticscholar.org/paper/b592c88fb95851c920810c0cb00b3a497eab2d4a", + "title": "Tyrosine Kinase BMX Phosphorylates Phosphotyrosine-Primed Motif + Mediating the Activation of Multiple Receptor Tyrosine Kinases", "abstract": + "The tyrosine kinase BMX targets primed tyrosines in other tyrosine kinases + for full activation. Primed for Activation Various tyrosine kinases have dual + tyrosine motifs in their kinase domains. Phosphorylation of the first is necessary + for activity, but full activation requires phosphorylation of the second. + Chen et al. showed that in vitro BMX (bone marrow tyrosine kinase gene on + chromosome X) has a preference for these primed \u201cpYY\u201d motifs, only + phosphorylating the second tyrosine if the first is already phosphorylated. + Loss of BMX activity reduced FAK (focal adhesion kinase) activity and insulin + receptor signaling, suggesting that BMX may enhance signaling by various tyrosine + kinases that contain the pYY motif. These findings reveal a previously uncharacterized + property of BMX that may be involved in the regulation of multiple tyrosine + kinase pathways. The nonreceptor tyrosine kinase BMX (bone marrow tyrosine + kinase gene on chromosome X) is abundant in various cell types and activated + downstream of phosphatidylinositol-3 kinase (PI3K) and the kinase Src, but + its substrates are unknown. Positional scanning peptide library screening + revealed a marked preference for a priming phosphorylated tyrosine (pY) in + the \u22121 position, indicating that BMX substrates may include multiple + tyrosine kinases that are fully activated by pYpY sites in the kinase domain. + BMX phosphorylated focal adhesion kinase (FAK) at Tyr577 subsequent to its + Src-mediated phosphorylation at Tyr576. Loss of BMX by RNA interference or + by genetic deletion in mouse embryonic fibroblasts (MEFs) markedly impaired + FAK activity. Phosphorylation of the insulin receptor in the kinase domain + at Tyr1189 and Tyr1190, as well as Tyr1185, and downstream phosphorylation + of the kinase AKT at Thr308 were similarly impaired by BMX deficiency. However, + insulin-induced phosphorylation of AKT at Ser473 was not impaired in Bmx knockout + MEFs or liver tissue from Bmx knockout mice, which also showed increased insulin-stimulated + glucose uptake, possibly because of decreased abundance of the phosphatase + PHLPP (PH domain leucine-rich repeat protein phosphatase). Thus, by identifying + the pYpY motif as a substrate for BMX, our findings suggest that BMX functions + as a central regulator among multiple signaling pathways mediated by tyrosine + kinases.", "venue": "Science Signaling", "year": 2013, "referenceCount": 67, + "citationCount": 20, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3735445?pdf=render", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-05-28", "journal": {"volume": + "6", "pages": "ra40 - ra40", "name": "Science Signaling"}, "authors": [{"authorId": + "3571199", "name": "Sen Chen"}, {"authorId": "2177467180", "name": "Xinnong + Jiang"}, {"authorId": "7739224", "name": "C. Gewinner"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "38106639", "name": "Nicholas I. Simon"}, + {"authorId": "143967294", "name": "C. Cai"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6189162", "name": "S. Balk"}]}, {"paperId": "b6276ce7143ecbbe846af012cc9beb206157a1b9", + "externalIds": {"MAG": "2074790072", "DOI": "10.1073/pnas.1305286110", "CorpusId": + 25414810, "PubMed": "23589871"}, "corpusId": 25414810, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b6276ce7143ecbbe846af012cc9beb206157a1b9", + "title": "Phosphoinositides and membrane curvature switch the mode of actin + polymerization via selective recruitment of toca-1 and Snx9", "abstract": + "The membrane\u2013cytosol interface is the major locus of control of actin + polymerization. At this interface, phosphoinositides act as second messengers + to recruit membrane-binding proteins. We show that curved membranes, but not + flat ones, can use phosphatidylinositol 3-phosphate [PI(3)P] along with phosphatidylinositol + 4,5-bisphosphate [PI(4,5)P2] to stimulate actin polymerization. In this case, + actin polymerization requires the small GTPase cell cycle division 42 (Cdc42), + the nucleation-promoting factor neural Wiskott\u2013Aldrich syndrome protein + (N-WASP) and the actin nucleator the actin-related protein (Arp) 2/3 complex. + In liposomes containing PI(4,5)P2 as the sole phosphoinositide, actin polymerization + requires transducer of Cdc42 activation-1 (toca-1). In the presence of phosphatidylinositol + 3-phosphate, polymerization is both more efficient and independent of toca-1. + Under these conditions, sorting nexin 9 (Snx9) can be implicated as a specific + adaptor that replaces toca-1 to mobilize neural Wiskott\u2013Aldrich syndrome + protein and the Arp2/3 complex. This switch in phosphoinositide and adaptor + specificity for actin polymerization from membranes has implications for how + different types of actin structures are generated at precise times and locations + in the cell.", "venue": "Proceedings of the National Academy of Sciences", + "year": 2013, "referenceCount": 28, "citationCount": 57, "influentialCitationCount": + 6, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3645562?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-04-15", "journal": {"volume": + "110", "pages": "7193 - 7198", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "40618124", "name": "J. Gallop"}, + {"authorId": "5927133", "name": "A. Walrant"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "40294231", "name": "M. Kirschner"}]}, {"paperId": + "c2210b2adaca30c2c12ae946a3c7ccf326698750", "externalIds": {"PubMedCentral": + "3542272", "MAG": "2134189462", "DOI": "10.1371/journal.pone.0054127", "CorpusId": + 6235017, "PubMed": "23326584"}, "corpusId": 6235017, "publicationVenue": {"id": + "0aed7a40-85f3-4c66-9e1b-c1556c57001b", "name": "PLoS ONE", "type": "journal", + "alternate_names": ["Plo ONE", "PLOS ONE", "PLO ONE"], "issn": "1932-6203", + "url": "https://journals.plos.org/plosone/", "alternate_urls": ["http://www.plosone.org/"]}, + "url": "https://www.semanticscholar.org/paper/c2210b2adaca30c2c12ae946a3c7ccf326698750", + "title": "A Homogeneous, High-Throughput Assay for Phosphatidylinositol 5-Phosphate + 4-Kinase with a Novel, Rapid Substrate Preparation", "abstract": "Phosphoinositide + kinases regulate diverse cellular functions and are important targets for + therapeutic development for diseases, such as diabetes and cancer. Preparation + of the lipid substrate is crucial for the development of a robust and miniaturizable + lipid kinase assay. Enzymatic assays for phosphoinositide kinases often use + lipid substrates prepared from lyophilized lipid preparations by sonication, + which result in variability in the liposome size from preparation to preparation. + Herein, we report a homogeneous 1536-well luciferase-coupled bioluminescence + assay for PI5P4K\u03b1. The substrate preparation is novel and allows the + rapid production of a DMSO-containing substrate solution without the need + for lengthy liposome preparation protocols, thus enabling the scale-up of + this traditionally difficult type of assay. The Z\u2019-factor value was greater + than 0.7 for the PI5P4K\u03b1 assay, indicating its suitability for high-throughput + screening applications. Tyrphostin AG-82 had been identified as an inhibitor + of PI5P4K\u03b1 by assessing the degree of phospho transfer of \u03b3-32P-ATP + to PI5P; its inhibitory activity against PI5P4K\u03b1 was confirmed in the + present miniaturized assay. From a pilot screen of a library of bioactive + compounds, another tyrphostin, I-OMe tyrphostin AG-538 (I-OMe-AG-538), was + identified as an ATP-competitive inhibitor of PI5P4K\u03b1 with an IC50 of + 1 \u00b5M, affirming the suitability of the assay for inhibitor discovery + campaigns. This homogeneous assay may apply to other lipid kinases and should + help in the identification of leads for this class of enzymes by enabling + high-throughput screening efforts.", "venue": "PLoS ONE", "year": 2013, "referenceCount": + 49, "citationCount": 42, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054127&type=printable", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-01-10", "journal": {"volume": + "8", "name": "PLoS ONE"}, "authors": [{"authorId": "29195749", "name": "Mindy + I. Davis"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "145829790", + "name": "M. Shen"}, {"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "29274858", "name": "Natasha Thorne"}, {"authorId": "88898503", "name": "Sam + Michael"}, {"authorId": "5123505", "name": "R. Pragani"}, {"authorId": "3275486", + "name": "M. Boxer"}, {"authorId": "49715313", "name": "K. Sumita"}, {"authorId": + "2775065", "name": "K. Takeuchi"}, {"authorId": "2607088", "name": "D. Auld"}, + {"authorId": "4837727", "name": "Zhuyin Li"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "145183304", "name": "A. Simeonov"}]}, {"paperId": + "c58404c7676f2a2bfc1891eb5a301c10eb11e3fc", "externalIds": {"MAG": "2056077438", + "DOI": "10.1126/science.1226603", "CorpusId": 31810174, "PubMed": "23118012"}, + "corpusId": 31810174, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/c58404c7676f2a2bfc1891eb5a301c10eb11e3fc", + "title": "Influence of Threonine Metabolism on S-Adenosylmethionine and Histone + Methylation", "abstract": "SAM, Histones, and Stem Cells Mouse embryonic stem + cells require threonine for growth and express large amounts of the enzyme + that catalyzes the first step in threonine metabolism. To find out what is + so important about threonine in these cells, Shyh-Change et al. (p. 222, published + online 1 November; see the Perspective by Sassone-Corsi) monitored changes + in metabolism by mass spectrometry in induced pluripotent stem cells. Threonine + was required to maintain cellular concentrations of S-adenosylmethionine (SAM), + a substrate used for protein methylation. Restriction of threonine inhibited + methylation of histones, which is characteristic of chromatin in embryonic + stem cells. Thus, altered metabolism of threonine and methionine in stem cells + may be linked to epigenetic changes that influence genetic reprogramming and + decisions of stem cells to proliferate or differentiate. Unusual threonine + metabolism in mouse stem cells influences genetic reprogramming via altered + histone methylation. [Also see Perspective by Sassone-Corsi] Threonine is + the only amino acid critically required for the pluripotency of mouse embryonic + stem cells (mESCs), but the detailed mechanism remains unclear. We found that + threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent + stem cells, resulting in regulation of histone methylation. Isotope labeling + of mESCs revealed that threonine provides a substantial fraction of both the + cellular glycine and the acetyl\u2013coenzyme A (CoA) needed for SAM synthesis. + Depletion of threonine from the culture medium or threonine dehydrogenase + (Tdh) from mESCs decreased accumulation of SAM and decreased trimethylation + of histone H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation. + Thus, abundance of SAM appears to influence H3K4me3, providing a possible + mechanism by which modulation of a metabolic pathway might influence stem + cell fate.", "venue": "Science", "year": 2013, "referenceCount": 25, "citationCount": + 507, "influentialCitationCount": 39, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3652341?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-01-11", "journal": {"volume": "339", "pages": "222 + - 226", "name": "Science"}, "authors": [{"authorId": "1397529716", "name": + "Ng Shyh\u2010Chang"}, {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "1723564", "name": "Yuxiang + Zheng"}, {"authorId": "50651504", "name": "Ren Yi Teo"}, {"authorId": "5878690", + "name": "Sutheera Ratanasirintrawoot"}, {"authorId": "2117170793", "name": + "Jin Zhang"}, {"authorId": "5073178", "name": "T. Onder"}, {"authorId": "38764542", + "name": "J. Unternaehrer"}, {"authorId": "2115313565", "name": "Hao Zhu"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "2028224", "name": + "G. Daley"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d5f0deec0d40cdd4575cc96248ebfd0ef2156d58", "externalIds": {"MAG": "2158076290", + "DOI": "10.1158/0008-5472.CAN-13-0080", "CorpusId": 749004, "PubMed": "23687346"}, + "corpusId": 749004, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/d5f0deec0d40cdd4575cc96248ebfd0ef2156d58", + "title": "Metformin decreases glucose oxidation and increases the dependency + of prostate cancer cells on reductive glutamine metabolism.", "abstract": + "Metformin inhibits cancer cell proliferation, and epidemiology studies suggest + an association with increased survival in patients with cancer taking metformin; + however, the mechanism by which metformin improves cancer outcomes remains + controversial. To explore how metformin might directly affect cancer cells, + we analyzed how metformin altered the metabolism of prostate cancer cells + and tumors. We found that metformin decreased glucose oxidation and increased + dependency on reductive glutamine metabolism in both cancer cell lines and + in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in + the presence of metformin further attenuated proliferation, whereas increasing + glutamine metabolism rescued the proliferative defect induced by metformin. + These data suggest that interfering with glutamine may synergize with metformin + to improve outcomes in patients with prostate cancer.", "venue": "Cancer Research", + "year": 2013, "referenceCount": 67, "citationCount": 194, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3930683?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2013-05-01", "journal": + {"volume": "73 14", "pages": "\n 4429-38\n ", "name": "Cancer + research"}, "authors": [{"authorId": "46775302", "name": "S. Fendt"}, {"authorId": + "49200178", "name": "E. Bell"}, {"authorId": "4181119", "name": "Mark A Keibler"}, + {"authorId": "34711277", "name": "Shawn M. Davidson"}, {"authorId": "3495178", + "name": "G. Wirth"}, {"authorId": "8143199", "name": "B. Fiske"}, {"authorId": + "34534173", "name": "Jared R Mayers"}, {"authorId": "145780106", "name": "M. + Schwab"}, {"authorId": "5679020", "name": "G. Bellinger"}, {"authorId": "6688912", + "name": "A. Csibi"}, {"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "101487845", "name": "M. Blouin"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4148406", "name": "L. Guarente"}, {"authorId": "4037343", "name": + "J. Blenis"}, {"authorId": "78091495", "name": "M. Pollak"}, {"authorId": + "4680166", "name": "A. Olumi"}, {"authorId": "3804233", "name": "M. V. Vander + Heiden"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}]}, {"paperId": + "d6e11f49978c4ae02ac94fad7d8e172812c1ffb5", "externalIds": {"DOI": "10.1096/fasebj.27.1_supplement.1046.3", + "CorpusId": 249766417}, "corpusId": 249766417, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/d6e11f49978c4ae02ac94fad7d8e172812c1ffb5", + "title": "Ras Activity Regulation by Monoubiquitination", "abstract": "Ras + proteins are critical regulators of cellular growth. The population of activated, + GTP\u2010bound Ras in normal cells is controlled by protein regulators. Oncogenic + mutations promote activation by populating the active state of Ras, most frequently + by impairing the action of proteins that downregulate its activity. Recently, + a novel mechanism of Ras activation was identified, in which modification + by ubiquitination was found to populate Ras in its active GTP\u2010bound state, + enhance interactions with downstream effectors and promote Ras\u2010mediated + tumorigenesis. These findings represent a paradigm shift in our understanding + of the role monoubiquitination may play in protein regulation. By conducting + NMR, modeling, biochemical and biological studies, we find that monoubiquitination + of Ras at position 147 has little effect on intrinsic guanine nucleotide binding + or hydrolysis, but impairs the ability of GTPase activating proteins to downregulate + Ras activity, accounting for the accumulation of Ras\u2010GTP in cells. These + findings reveal that a post\u2010translational modification can disrupt protein + interactions that normally constrain cellular signaling and transformation.", + "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2013-04-01", "journal": {"volume": "27", "name": "The + FASEB Journal"}, "authors": [{"authorId": "46713144", "name": "S. Campbell"}, + {"authorId": "145564214", "name": "R. Baker"}, {"authorId": "7268742", "name": + "Steven M. Lewis"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": + "5527411", "name": "Emily M. Wilkerson"}, {"authorId": "2268976", "name": + "J. Locasale"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144226889", "name": "B. Kuhlman"}, {"authorId": "1710306", "name": "H. Dohlman"}]}, + {"paperId": "dc41a0f23842d7cffc7494912ed6724d82a683ae", "externalIds": {"MAG": + "1975075263", "DOI": "10.1158/1538-7445.AM2013-4588", "CorpusId": 58742110}, + "corpusId": 58742110, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/dc41a0f23842d7cffc7494912ed6724d82a683ae", + "title": "Abstract 4588: Identification of CDCP1 as a HIF-2\u03b1 target gene + involved in the regulation of cancer cell migration and metastasis.", "abstract": + "CUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is + highly expressed in stem cells and frequently overexpressed and tyrosine phosphorylated + in cancer. CDCP1 promotes cancer cell metastasis. However, the mechanisms + that regulate CDCP1 are not well defined. Studies from our laboratory revealed + a biochemical pathway by which CDCP1 participates in the activation of Src-family + kinase (SFK) members and the coupling of SFK-activation to the phosphorylation + and regulation of protein kinase C-delta (PKC-\u03b4). Here we show that hypoxia + induces CDCP1 expression and tyrosine phosphorylation in a HIF-2\u03b1, but + not HIF-1\u03b1, dependent fashion. shRNA knockdown of CDCP1 impairs cancer + cell migration under hypoxic conditions, while overexpression of HIF-2\u03b1 + promotes the growth of tumor xenografts in association with enhanced CDCP1 + expression and tyrosine phosphorylation, as well as, significantly promotes + lung metastases in NOD/SCID mice. To investigate the relationship between + HIF-2\u03b1 and CDCP1 expression, we performed a correlation analysis in the + largest up-to-date collection (Sanger Cell Line Project) of cancer cell line + microarray data (n=732). We found a dramatic concordance in the expression + of HIF-2\u03b1 and CDCP1 (Pearson9s correlation, P Supported by NIH grant + 5R01GM056203-15 to L.C.C and Dana Farber/Harvard Cancer Center Career Development + Award to B.M.E. Citation Format: Brooke M. Emerling, Cyril Benes, Eric Bell, + George Poulogiannis, Kevin Courtney, Hui Lui, Rayman Choo-Wing, Gary Bellinger, + Stephen Soltoff, Lewis Cantley. Identification of CDCP1 as a HIF-2\u03b1 target + gene involved in the regulation of cancer cell migration and metastasis. [abstract]. + In: Proceedings of the 104th Annual Meeting of the American Association for + Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer + Res 2013;73(8 Suppl):Abstract nr 4588. doi:10.1158/1538-7445.AM2013-4588", + "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2013-04-15", "journal": {"volume": "73", "pages": "4588-4588", "name": "Cancer + Research"}, "authors": [{"authorId": "5542751", "name": "B. Emerling"}, {"authorId": + "1714039", "name": "C. Benes"}, {"authorId": "49200178", "name": "E. Bell"}, + {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": "13782167", + "name": "K. Courtney"}, {"authorId": "47028670", "name": "H. Lui"}, {"authorId": + "1401641678", "name": "R. Choo-Wing"}, {"authorId": "5679020", "name": "G. + Bellinger"}, {"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "df9a0a200e678d9c31d9c9ffc18916ed0b6cb21b", + "externalIds": {"MAG": "2059380603", "DOI": "10.1038/emboj.2013.186", "CorpusId": + 7791738, "PubMed": "24013118"}, "corpusId": 7791738, "publicationVenue": {"id": + "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": "journal", + "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", "url": + "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/df9a0a200e678d9c31d9c9ffc18916ed0b6cb21b", + "title": "FoxO3 coordinates metabolic pathways to maintain redox balance in + neural stem cells", "abstract": null, "venue": "EMBO Journal", "year": 2013, + "referenceCount": 71, "citationCount": 110, "influentialCitationCount": 5, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3791369?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-10-02", "journal": {"volume": + "32", "name": "The EMBO Journal"}, "authors": [{"authorId": "4250474", "name": + "H. Yeo"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "2108446203", + "name": "Yuqing Zhang"}, {"authorId": "33312849", "name": "H. Ying"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5056578", "name": "J. Paik"}]}, {"paperId": "dffe20ab2c4e73bae7598baa2c68d8a70444d3b6", + "externalIds": {"MAG": "2056078734", "PubMedCentral": "3909335", "DOI": "10.1186/1741-7007-12-8", + "CorpusId": 33254184, "PubMed": "24484968"}, "corpusId": 33254184, "publicationVenue": + {"id": "1617f5c3-5410-462d-91c9-7aa8ced2d91d", "name": "BMC Biology", "type": + "journal", "issn": "1741-7007", "url": "http://www.biomedcentral.com/1741-7007/", + "alternate_urls": ["http://www.biomedcentral.com/bmcbiol/", "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=215"]}, + "url": "https://www.semanticscholar.org/paper/dffe20ab2c4e73bae7598baa2c68d8a70444d3b6", + "title": "Cancer, metabolism, fructose, artificial sweeteners, and going cold + turkey on sugar", "abstract": null, "venue": "BMC Biology", "year": 2013, + "referenceCount": 7, "citationCount": 15, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://bmcbiol.biomedcentral.com/track/pdf/10.1186/1741-7007-12-8", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2013-01-31", "journal": {"volume": "12", "pages": + "8 - 8", "name": "BMC Biology"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "e0c356adeecdf5655e7bfb0266a33bc8dfea8835", "externalIds": + {"MAG": "2101774229", "DOI": "10.1073/pnas.1317577110", "CorpusId": 24903326, + "PubMed": "24145418"}, "corpusId": 24903326, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/e0c356adeecdf5655e7bfb0266a33bc8dfea8835", + "title": "Phenformin enhances the therapeutic benefit of BRAFV600E inhibition + in melanoma", "abstract": "Significance Inhibitors of BRAF protein kinase, + such as Vemurafenib and Dabrafenib, have shown remarkable antitumor activity + in patients with BRAF mutant melanoma. However, most of the patients developed + drug resistance during the course of treatment, leading to resumed tumor growth. + This drug resistance challenge underscores the need to improve on current + BRAF-targeted therapy. In this study, we have shown that phenformin, a biguanide + used for treating type 2 diabetes, enhances the antitumor activities of BRAF + inhibitors in both cultured melanoma cells and a genetically engineered BRAFV600E-driven + mouse model of melanoma. Our preclinical findings suggest that combining phenformin + with a BRAF inhibitor may be a more effective treatment than a single-agent + BRAF inhibitor for treating patients with melanoma whose tumor harbor BRAF + mutations. Biguanides, such as the diabetes therapeutics metformin and phenformin, + have demonstrated antitumor activity both in vitro and in vivo. The energy-sensing + AMP-activated protein kinase (AMPK) is known to be a major cellular target + of biguanides. Based on our discovery of cross-talk between the AMPK and v-Raf + murine sarcoma viral oncogene homolog B1 (BRAF) signaling pathways, we investigated + the antitumor effects of combining phenformin with a BRAF inhibitor PLX4720 + on the proliferation of BRAF-mutated melanoma cells in vitro and on BRAF-driven + tumor growth in vivo. Cotreatment of BRAF-mutated melanoma cell lines with + phenformin and PLX4720 resulted in synergistic inhibition of cell viability, + compared with the effects of the single agent alone. Moreover, treatment with + phenformin significantly delayed the development of resistance to PLX4720 + in cultured melanoma cells. Biochemical analyses showed that phenformin and + PLX4720 exerted cooperative effects on inhibiting mTOR signaling and inducing + apoptosis. Noticeably, phenformin selectively targeted subpopulations of cells + expressing JARID1B, a marker for slow cycling melanoma cells, whereas PLX4720 + selectively targeted JARID1B-negative cells. Finally, in contrast to their + use as single agents, the combination of phenformin and PLX4720 induced tumor + regression in both nude mice bearing melanoma xenografts and in a genetically + engineered BRAFV600E/PTENnull-driven mouse model of melanoma. These results + strongly suggest that significant therapeutic advantage may be achieved by + combining AMPK activators such as phenformin with BRAF inhbitors for the treatment + of melanoma.", "venue": "Proceedings of the National Academy of Sciences", + "year": 2013, "referenceCount": 32, "citationCount": 192, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3831456?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-10-21", "journal": {"volume": "110", "pages": "18226 + - 18231", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "23576567", "name": "P. Yuan"}, {"authorId": "2111361747", "name": + "Koichi Ito"}, {"authorId": "1398525526", "name": "R. P\u00e9rez-Lorenzo"}, + {"authorId": "1521983646", "name": "Christina A. Del Guzzo"}, {"authorId": + "2141765417", "name": "Jung Hyun Lee"}, {"authorId": "83946576", "name": "Che-Hung + Shen"}, {"authorId": "4177474", "name": "M. Bosenberg"}, {"authorId": "144508121", + "name": "M. McMahon"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "143918840", "name": "B. Zheng"}]}, {"paperId": "e3731c2c2496d8a2d364ca8952db4489bf9d10bd", + "externalIds": {"MAG": "2466818859", "CorpusId": 88979582}, "corpusId": 88979582, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e3731c2c2496d8a2d364ca8952db4489bf9d10bd", + "title": "Figure 2, [A) Hypoxia and exogenous oxidants...].", "abstract": + null, "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}], "publicationTypes": null, "publicationDate": "2013-05-08", + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "2435894", + "name": "K. Brimacombe"}, {"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "6351971", "name": "B. Hong"}, {"authorId": "5566934", "name": + "W. Tempel"}, {"authorId": "33892021", "name": "S. Dimov"}, {"authorId": "1799343", + "name": "H. Veith"}, {"authorId": "2607088", "name": "D. Auld"}, {"authorId": + "35413264", "name": "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig + J. Thomas"}, {"authorId": "2790262", "name": "Hee-won Park"}, {"authorId": + "145829790", "name": "M. Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3275486", "name": "M. Boxer"}]}, {"paperId": "ebd6e44bfea315072c0f6b7399186e20968fe4c1", + "externalIds": {"MAG": "256459495", "CorpusId": 83344047}, "corpusId": 83344047, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/ebd6e44bfea315072c0f6b7399186e20968fe4c1", + "title": "ML285 affects reactive oxygen species\u2019 inhibition of pyruvate + kinase M2", "abstract": null, "venue": "", "year": 2013, "referenceCount": + 0, "citationCount": 11, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Computer Science", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2013-05-08", + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "2435894", + "name": "K. Brimacombe"}, {"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "6351971", "name": "B. Hong"}, {"authorId": "5566934", "name": + "W. Tempel"}, {"authorId": "33892021", "name": "S. Dimov"}, {"authorId": "1799343", + "name": "H. Veith"}, {"authorId": "2607088", "name": "D. Auld"}, {"authorId": + "35413264", "name": "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig + J. Thomas"}, {"authorId": "2790262", "name": "Hee-won Park"}, {"authorId": + "145829790", "name": "M. Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3275486", "name": "M. Boxer"}]}, {"paperId": "ef0a73612aff3f9f580a06ec5607d14cec462f3b", + "externalIds": {"MAG": "2399983558", "CorpusId": 99302190}, "corpusId": 99302190, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/ef0a73612aff3f9f580a06ec5607d14cec462f3b", + "title": "Figure 1, Previously reported PKM2 activator ML probes", "abstract": + null, "venue": "", "year": 2013, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-05-08", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "2435894", "name": "K. Brimacombe"}, + {"authorId": "46996935", "name": "D. Anastasiou"}, {"authorId": "6351971", + "name": "B. Hong"}, {"authorId": "5566934", "name": "W. Tempel"}, {"authorId": + "33892021", "name": "S. Dimov"}, {"authorId": "1799343", "name": "H. Veith"}, + {"authorId": "2607088", "name": "D. Auld"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "2148769632", "name": "Craig J. Thomas"}, {"authorId": + "2790262", "name": "Hee-won Park"}, {"authorId": "145829790", "name": "M. + Shen"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3275486", + "name": "M. Boxer"}]}, {"paperId": "ef15ca796d4265a9dcff47d3bed7d5f4a67359cc", + "externalIds": {"PubMedCentral": "3787876", "MAG": "2151419509", "DOI": "10.1038/ng.2650", + "CorpusId": 7036669, "PubMed": "23727860"}, "corpusId": 7036669, "publicationVenue": + {"id": "bb27e645-e57c-42c3-bcbc-c7b443c58209", "name": "Nature Genetics", + "type": "journal", "alternate_names": ["Nat Genet"], "issn": "1061-4036", + "url": "http://www.nature.com/ng/", "alternate_urls": ["http://www.nature.com/ng/index.html"]}, + "url": "https://www.semanticscholar.org/paper/ef15ca796d4265a9dcff47d3bed7d5f4a67359cc", + "title": "A co-clinical approach identifies mechanisms and potential therapies + for androgen deprivation resistance in prostate cancer", "abstract": null, + "venue": "Nature Genetics", "year": 2013, "referenceCount": 53, "citationCount": + 133, "influentialCitationCount": 14, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3787876?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2013-05-21", "journal": {"volume": "45", "pages": "747 + - 755", "name": "Nature genetics"}, "authors": [{"authorId": "5729169", "name": + "A. Lunardi"}, {"authorId": "2901501", "name": "U. Ala"}, {"authorId": "4276612", + "name": "M. Epping"}, {"authorId": "6316033", "name": "L. Salmena"}, {"authorId": + "4102988", "name": "J. Clohessy"}, {"authorId": "4817196", "name": "Kaitlyn + A. Webster"}, {"authorId": "47227159", "name": "Guocan Wang"}, {"authorId": + "3778026", "name": "R. Mazzucchelli"}, {"authorId": "144862941", "name": "M. + Bianconi"}, {"authorId": "5592639", "name": "E. Stack"}, {"authorId": "50267670", + "name": "R. Lis"}, {"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5854981", "name": "G. Bubley"}, + {"authorId": "13870598", "name": "C. Cordon-Cardo"}, {"authorId": "3950794", + "name": "W. Gerald"}, {"authorId": "145421680", "name": "R. Montironi"}, {"authorId": + "7505152", "name": "S. Signoretti"}, {"authorId": "6213932", "name": "M. Loda"}, + {"authorId": "3547827", "name": "C. Nardella"}, {"authorId": "4499580", "name": + "P. Pandolfi"}]}, {"paperId": "f00a6d08a329a4c52b7d96f28a13ce8bfda374f2", + "externalIds": {"MAG": "2095088245", "DOI": "10.1158/0008-5472.SABCS13-OT1-4-02", + "CorpusId": 73181944}, "corpusId": 73181944, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/f00a6d08a329a4c52b7d96f28a13ce8bfda374f2", + "title": "Abstract OT1-4-02: Phase I study of the combination of BKM120 and + olaparib for the treatment of high grade serous ovarian cancer (HGSC) and + triple negative breast cancer (TNBC)", "abstract": "Background: In vivo synergy + of the PI3-kinase inhibitor BKM120 with the PARP inhibitor olaparib has been + observed using a mouse model of BRCA1-related breast cancer and sporadic TNBC + (Juvekar et al and Ibrahim et al, Cancer Discovery 2012). In addition, olaparib + has single agent activity in both HGSC and BRCA-associated breast cancer. + The PI3kinase pathway is activated in both TNBC and HGSC (www.cancergenome.nih.gov). + These preclinical and clinical data have served as the rationale for this + phase I, multi-center study (NCT01623349) combining the oral PARP inhibitor + olaparib with the oral PI3-kinase inhibitor BKM120 in patients with recurrent + HGSC or recurrent TNBC. This study is being conducted through the Stand Up + to Cancer (SU2C)9s Targeting PI3-kinase in Women9s Cancers Dream Team. Study + Design: This study has a 3 + 3 design, escalating if 0/3 or 1/6 participants + have a dose limiting toxicity (DLT) during the first cycle of therapy (first + 28 days). The study objectives are to determine the recommended phase II dose + (RP2D) of daily continuous oral olaparib (using the tablet formulation) and + BKM120, assess toxicities, safety, and preliminary activity of this combination, + and determine pharmacokinetic profiles of both agents. In addition, there + are several translational endpoints including elucidation of downstream signaling + effects of the PI3-kinase pathway, examination of BRCA1 immunostaining, and + assessment of BRCA1 promoter hypermethylation and somatic mutations in BRCA1 + and BRCA2 using archived formalin fixed paraffin embedded (FFPE) tissue. Serial + IL-8 and circulating DNA levels are also being monitored as well. Eligibility + includes a diagnosis of recurrent TNBC or HGSC, PS 0 or 1, measurable or evaluable + cancer, and normal lab values and organ function. Prior PARP inhibitor exposure + is allowed. In addition, breast cancer or ovarian cancer patients with any + histologic subtype are eligible if they have a known germline BRCA1 or BRCA2 + mutation. At the RP2D, 10 pts each with a diagnosis of TNBC or HGSC will be + enrolled to further determine safety and efficacy profiles in addition to + more thoroughly studying translational endpoints. As of June 7, 2013, 16 patients + have been enrolled into this study with a planned accrual of approximately + 50 patients which may change based on number of dose levels tested during + dose escalation. In addition, an amendment is pending that will add a second + cohort studying the combination of olaparib and BYL719 based on robust pre-clinical + activity observed in murine models which will increase our total accrual. + Once this new cohort is open, both arms will enroll simultaneously. For further + information, contact Ursula Matulonis at: umatulonis@partners.org. Citation + Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT1-4-02.", "venue": + "", "year": 2013, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2013-12-15", "journal": {"volume": + "73", "name": "Cancer Research"}, "authors": [{"authorId": "6927295", "name": + "U. Matulonis"}, {"authorId": "31554501", "name": "G. Wulf"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2241330", "name": "G. Mills"}, + {"authorId": "12796173", "name": "B. Lasonde"}, {"authorId": "40371034", "name": + "T. Atkinson"}, {"authorId": "122974814", "name": "C. Whalen"}, {"authorId": + "4327978", "name": "S. Isakoff"}, {"authorId": "2974900", "name": "S. Westin"}, + {"authorId": "1397923721", "name": "K. Bell-McGuinn"}, {"authorId": "2369378", + "name": "E. Winer"}]}, {"paperId": "f303d8aeead0055ee1ca14a8147e4caab66d1857", + "externalIds": {"MAG": "2004170579", "DOI": "10.1016/j.molcel.2013.01.035", + "CorpusId": 206986841, "PubMed": "23453806"}, "corpusId": 206986841, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/f303d8aeead0055ee1ca14a8147e4caab66d1857", + "title": "AMPK-dependent degradation of TXNIP upon energy stress leads to + enhanced glucose uptake via GLUT1.", "abstract": null, "venue": "Molecules + and Cells", "year": 2013, "referenceCount": 51, "citationCount": 455, "influentialCitationCount": + 35, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276513000993/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-03-28", "journal": {"volume": + "49 6", "pages": "\n 1167-75\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "145650836", "name": "N. Wu"}, {"authorId": "143918840", + "name": "B. Zheng"}, {"authorId": "4635185", "name": "A. Shaywitz"}, {"authorId": + "3734143", "name": "Y. Dagon"}, {"authorId": "40500196", "name": "Christine + M Tower"}, {"authorId": "5679020", "name": "G. Bellinger"}, {"authorId": "83946576", + "name": "Che-Hung Shen"}, {"authorId": "50976006", "name": "Jennifer Wen"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "32665208", "name": + "T. McGraw"}, {"authorId": "1997179", "name": "B. Kahn"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "feb70ba005051b17138728accca3fd6d4e7854fc", + "externalIds": {"MAG": "2030991075", "DOI": "10.1073/pnas.1222435110", "CorpusId": + 25668816, "PubMed": "23378636"}, "corpusId": 25668816, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/feb70ba005051b17138728accca3fd6d4e7854fc", + "title": "Identification of CDCP1 as a hypoxia-inducible factor 2\u03b1 (HIF-2\u03b1) + target gene that is associated with survival in clear cell renal cell carcinoma + patients", "abstract": "CUB domain-containing protein 1 (CDCP1) is a transmembrane + protein that is highly expressed in stem cells and frequently overexpressed + and tyrosine-phosphorylated in cancer. CDCP1 promotes cancer cell metastasis. + However, the mechanisms that regulate CDCP1 are not well-defined. Here we + show that hypoxia induces CDCP1 expression and tyrosine phosphorylation in + hypoxia-inducible factor (HIF)-2\u03b1\u2013, but not HIF-1\u03b1\u2013, dependent + fashion. shRNA knockdown of CDCP1 impairs cancer cell migration under hypoxic + conditions, whereas overexpression of HIF-2\u03b1 promotes the growth of tumor + xenografts in association with enhanced CDCP1 expression and tyrosine phosphorylation. + Immunohistochemistry analysis of tissue microarray samples from tumors of + patients with clear cell renal cell carcinoma shows that increased CDCP1 expression + correlates with decreased overall survival. Together, these data support a + critical role for CDCP1 as a unique HIF-2\u03b1 target gene involved in the + regulation of cancer metastasis, and suggest that CDCP1 is a biomarker and + potential therapeutic target for metastatic cancers.", "venue": "Proceedings + of the National Academy of Sciences", "year": 2013, "referenceCount": 36, + "citationCount": 61, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/110/9/3483.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2013-02-01", "journal": {"volume": + "110", "pages": "3483 - 3488", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "5542751", "name": "B. Emerling"}, + {"authorId": "1714039", "name": "C. Benes"}, {"authorId": "4612853", "name": + "G. Poulogiannis"}, {"authorId": "49200178", "name": "E. Bell"}, {"authorId": + "13782167", "name": "K. Courtney"}, {"authorId": "2146671919", "name": "Hui + Liu"}, {"authorId": "1401641678", "name": "R. Choo-Wing"}, {"authorId": "5679020", + "name": "G. Bellinger"}, {"authorId": "8254104", "name": "Kazumi S. Tsukazawa"}, + {"authorId": "49917633", "name": "Victoria Brown"}, {"authorId": "7505152", + "name": "S. Signoretti"}, {"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "0b5af00901a54df3f6fb38987ba9d0d537c41350", + "externalIds": {"PubMedCentral": "3395034", "MAG": "2073112065", "DOI": "10.1186/1753-6561-6-S3-O2", + "CorpusId": 85358556}, "corpusId": 85358556, "publicationVenue": {"id": "5b9b6854-d895-439b-9ab4-1e1ed4c26336", + "name": "BMC Proceedings", "type": "journal", "alternate_names": ["BMC Proc"], + "issn": "1753-6561", "url": "http://www.biomedcentral.com/bmcproc", "alternate_urls": + ["http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=587"]}, + "url": "https://www.semanticscholar.org/paper/0b5af00901a54df3f6fb38987ba9d0d537c41350", + "title": "PI 3-kinase and disease", "abstract": null, "venue": "BMC Proceedings", + "year": 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2012-06-01", "journal": {"volume": "6", "pages": "O2 - O2", "name": "BMC + Proceedings"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "105a81b36eae76d87c687a783130b4e8c8ac19fe", "externalIds": {"PubMedCentral": + "4073074", "MAG": "1996390758", "DOI": "10.1186/1753-6561-6-S3-O2", "CorpusId": + 8936707}, "corpusId": 8936707, "publicationVenue": {"id": "5b9b6854-d895-439b-9ab4-1e1ed4c26336", + "name": "BMC Proceedings", "type": "journal", "alternate_names": ["BMC Proc"], + "issn": "1753-6561", "url": "http://www.biomedcentral.com/bmcproc", "alternate_urls": + ["http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=587"]}, + "url": "https://www.semanticscholar.org/paper/105a81b36eae76d87c687a783130b4e8c8ac19fe", + "title": "PI 3-kinase and disease", "abstract": null, "venue": "BMC Proceedings", + "year": 2014, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2014-05-28", "journal": {"volume": "2", "pages": "O30 - O30", "name": "Cancer + & Metabolism"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "150e78f416798147a8a164b104be10c5a196046f", "externalIds": {"MAG": + "2595755469", "DOI": "10.1038/NCHEMBIO1212-1008B", "CorpusId": 90537327}, + "corpusId": 90537327, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/150e78f416798147a8a164b104be10c5a196046f", + "title": "Erratum: Pyruvate kinase M2 activators promote tetramer formation + and suppress tumorigenesis (Nature Chemical Biology (2012) 8 (839-847))", + "abstract": null, "venue": "", "year": 2012, "referenceCount": 1, "citationCount": + 11, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/nchembio1212-1008b.pdf", "status": + null}, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2012-12-01", "journal": {"volume": + "8", "name": "Nature Chemical Biology"}, "authors": [{"authorId": "46996935", + "name": "D. Anastasiou"}, {"authorId": "1924735", "name": "Yimin Yu"}, {"authorId": + "5553029", "name": "W. J. Israelsen"}, {"authorId": "4084746", "name": "Jian-Kang + Jiang"}, {"authorId": "3275486", "name": "M. Boxer"}, {"authorId": "6351971", + "name": "B. Hong"}, {"authorId": "5566934", "name": "W. Tempel"}, {"authorId": + "33892021", "name": "S. Dimov"}, {"authorId": "145829790", "name": "M. Shen"}, + {"authorId": "38884428", "name": "Abhishek Jha"}, {"authorId": "47912756", + "name": "Hua Yang"}, {"authorId": "6160202", "name": "K. Mattaini"}, {"authorId": + "2281284", "name": "C. Metallo"}, {"authorId": "8143199", "name": "B. Fiske"}, + {"authorId": "13782167", "name": "K. Courtney"}, {"authorId": "3870192", "name": + "S. Malstrom"}, {"authorId": "47670281", "name": "Tahsin M. Khan"}, {"authorId": + "7636232", "name": "C. Kung"}, {"authorId": "5914392", "name": "A. P. Skoumbourdis"}, + {"authorId": "1799343", "name": "H. Veith"}, {"authorId": "49134285", "name": + "Noel Southall"}, {"authorId": "1699620778", "name": "M. Walsh"}, {"authorId": + "2435894", "name": "K. Brimacombe"}, {"authorId": "3802281", "name": "W. Leister"}, + {"authorId": "39089704", "name": "S. Lunt"}, {"authorId": "51164649", "name": + "Zachary R. Johnson"}, {"authorId": "4886372", "name": "K. Yen"}, {"authorId": + "8330889", "name": "K. Kunii"}, {"authorId": "34711277", "name": "Shawn M. + Davidson"}, {"authorId": "4164415", "name": "H. Christofk"}, {"authorId": + "4066869", "name": "C. Austin"}, {"authorId": "3155966", "name": "James Inglese"}, + {"authorId": "2087058005", "name": "M. H. Harris"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}, + {"authorId": "5908187", "name": "F. Salituro"}, {"authorId": "5210229", "name": + "Shengfang Jin"}, {"authorId": "38799894", "name": "L. Dang"}, {"authorId": + "2607088", "name": "D. Auld"}, {"authorId": "2790262", "name": "Hee-won Park"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2148769632", + "name": "Craig J. Thomas"}, {"authorId": "35413264", "name": "M. V. Heiden"}]}, + {"paperId": "18e214b3035e1ee89cd5c618366fbff1cecbcc2b", "externalIds": {"CorpusId": + 39822363}, "corpusId": 39822363, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/18e214b3035e1ee89cd5c618366fbff1cecbcc2b", + "title": "Cellular Control Mechanisms that Regulate Pyruvate Kinase M 2 Activity + and Promote Cancer Growth", "abstract": "Costas A. Lyssiotis, Dimitrios Anastasiou, + Jason W. Locasale, Matthew G. Vander Heiden, Heather R. Christofk, Lewis C. + Cantley* Division of Signal Transduction, Beth Israel Deacon ess Medical Center, + Harvard Medical School, Boston, MA 02115, USA. Department of Systems Biology, + Harvard Medical Scho ol, Boston, MA 02115, USA. Koch Institute for Integrative + Cancer Research, Dep artment of Biology, Massachusetts Institute of Tech nology, + Cambridge, MA 02139, USA. Department of Medical Oncology, Dana Farber Cancer + Institute, Harvard Medical School, Boston, MA 02115 , USA Institute for Molecular + Medicine, Department of Mol ecular and Medical Pharmacology, David Geffen + Schoo l of Medicine at UCLA, Los Angeles, CA 90095, USA.", "venue": "", "year": + 2012, "referenceCount": 33, "citationCount": 7, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "4901222", + "name": "C. Lyssiotis"}, {"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "4164415", "name": "H. Christofk"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "1a6677e1835c937e52e4676851cb301878c62ea3", + "externalIds": {"CorpusId": 207761373}, "corpusId": 207761373, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/1a6677e1835c937e52e4676851cb301878c62ea3", + "title": "Therapeutic Effects of Metformin The Kinase LKB 1 Mediates Glucose + Homeostasis in Liver and", "abstract": "clicking here. colleagues, clients, + or customers by , you can order high-quality copies for your If you wish to + distribute this article to others here. following the guidelines can be obtained + by Permission to republish or repurpose articles or portions of articles ): October + 4, 2012 www.sciencemag.org (this information is current as of The following + resources related to this article are available online at", "venue": "", "year": + 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "4426388", + "name": "R. Shaw"}, {"authorId": "5493258", "name": "K. Lamia"}, {"authorId": + "49440900", "name": "Debbie S. Vasquez"}, {"authorId": "1885308", "name": + "S. Koo"}, {"authorId": "5974412", "name": "N. Bardeesy"}, {"authorId": "5593407", + "name": "R. DePinho"}, {"authorId": "4892627", "name": "M. Montminy"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "1bf286996662a9e981621fdb5ab692ff480ce80f", + "externalIds": {"PubMedCentral": "3498106", "MAG": "2100647690", "DOI": "10.1371/journal.pone.0049466", + "CorpusId": 10830274, "PubMed": "23166678"}, "corpusId": 10830274, "publicationVenue": + {"id": "0aed7a40-85f3-4c66-9e1b-c1556c57001b", "name": "PLoS ONE", "type": + "journal", "alternate_names": ["Plo ONE", "PLOS ONE", "PLO ONE"], "issn": + "1932-6203", "url": "https://journals.plos.org/plosone/", "alternate_urls": + ["http://www.plosone.org/"]}, "url": "https://www.semanticscholar.org/paper/1bf286996662a9e981621fdb5ab692ff480ce80f", + "title": "Somatic Mutations of PIK3R1 Promote Gliomagenesis", "abstract": + "The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration + in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer + Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types, + but the tumorigenic activity of these mutations has not been demonstrated + in GBM. We show here that somatic mutations in the iSH2 domain of PIK3R1 act + as oncogenic driver events. Specifically, introduction of a subset of the + mutations identified in human GBM, in the nSH2 and iSH2 domains, increases + signaling through the PI3K pathway and promotes tumorigenesis of primary normal + human astrocytes in an orthotopic xenograft model. Furthermore, we show that + cells that are dependent on mutant P85\u03b1-mediated PI3K signaling exhibit + increased sensitivity to a small molecule inhibitor of AKT. Together, these + results suggest that GBM patients whose tumors carry mutant PIK3R1 alleles + may benefit from treatment with inhibitors of AKT.", "venue": "PLoS ONE", + "year": 2012, "referenceCount": 25, "citationCount": 48, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0049466&type=printable", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2012-11-14", "journal": {"volume": + "7", "name": "PLoS ONE"}, "authors": [{"authorId": "3696841", "name": "S. + Quayle"}, {"authorId": "46663676", "name": "Jennifer Y. Lee"}, {"authorId": + "50005741", "name": "L. W. Cheung"}, {"authorId": "49594724", "name": "L. + Ding"}, {"authorId": "5970725", "name": "R. Wiedemeyer"}, {"authorId": "31662497", + "name": "Robert W. Dewan"}, {"authorId": "1422124289", "name": "Emmet Huang-Hobbs"}, + {"authorId": "117378315", "name": "L. Zhuang"}, {"authorId": "2111010098", + "name": "R. Wilson"}, {"authorId": "5627829", "name": "K. Ligon"}, {"authorId": + "2241330", "name": "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "144750835", "name": "L. Chin"}]}, {"paperId": "280723b461d947331e65bf86d38d79d1319a67be", + "externalIds": {"MAG": "2324553530", "DOI": "10.1016/j.cell.2012.01.058", + "CorpusId": 16653547, "PubMed": "22541435"}, "corpusId": 16653547, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/280723b461d947331e65bf86d38d79d1319a67be", + "title": "Oncogenic Kras Maintains Pancreatic Tumors through Regulation of + Anabolic Glucose Metabolism", "abstract": null, "venue": "Cell", "year": 2012, + "referenceCount": 68, "citationCount": 1479, "influentialCitationCount": 91, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867412003522/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2012-04-27", "journal": {"volume": + "149", "pages": "656-670", "name": "Cell"}, "authors": [{"authorId": "33312849", + "name": "H. Ying"}, {"authorId": "4668673", "name": "A. Kimmelman"}, {"authorId": + "4901222", "name": "C. Lyssiotis"}, {"authorId": "50767858", "name": "S. Hua"}, + {"authorId": "2452535", "name": "G. Chu"}, {"authorId": "1400926643", "name": + "Eliot Fletcher-Sananikone"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "38313825", "name": "J. Son"}, {"authorId": "46702748", "name": + "Hailei Zhang"}, {"authorId": "3726846", "name": "J. L. Coloff"}, {"authorId": + "50017350", "name": "Hai-yan Yan"}, {"authorId": "47825035", "name": "Wei + Wang"}, {"authorId": "2144303098", "name": "Shujuan Chen"}, {"authorId": "49837367", + "name": "A. Viale"}, {"authorId": "145735876", "name": "Hongwu Zheng"}, {"authorId": + "5056578", "name": "J. Paik"}, {"authorId": "35160437", "name": "Carol S. + Lim"}, {"authorId": "145030722", "name": "A. Guimaraes"}, {"authorId": "47139219", + "name": "E. Martin"}, {"authorId": "153348414", "name": "Jeffery T. Chang"}, + {"authorId": "3721877", "name": "A. Hezel"}, {"authorId": "48157460", "name": + "S. R. Perry"}, {"authorId": "12879604", "name": "Jian Hu"}, {"authorId": + "1865086", "name": "B. Gan"}, {"authorId": "1824994", "name": "Yonghong Xiao"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "3127756", "name": + "R. Weissleder"}, {"authorId": "49416094", "name": "Y. A. Wang"}, {"authorId": + "144750835", "name": "L. Chin"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5593407", "name": "R. DePinho"}]}, {"paperId": "297a3affd56803e3d31f6291c08377563f805e25", + "externalIds": {"MAG": "2077672383", "DOI": "10.1158/0008-5472.SABCS12-MS1-1", + "CorpusId": 85286105}, "corpusId": 85286105, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/297a3affd56803e3d31f6291c08377563f805e25", + "title": "Abstract MS1-1: Targeting PI3K", "abstract": "Phosphoinositide 3-Kinase + (PI3K) is a central enzyme in a signaling pathway that mediates cellular responses + to growth factors. The signaling pathway downstream of PI3K is highly conserved + from worms and flies to humans and genetic analysis of the pathway has revealed + a conserved role in regulating glucose metabolism and cell growth. Mutational + events that lead to hyperactivation of the PI3K pathway result in hamartoma + syndromes and cancers. Activating mutations in PIK3CA, encoding the p110alpha + catalytic subunit of PI3K (PIK3CA) or inactivating mutations in PTEN, a phosphoinositide + 3-phosphatases that reverses the effects of PI3K, are among the most common + events in solid tumors, especially breast cancers. Drugs that target PI3K + are in clinical trials for a variety of cancers. It is likely that PI3K pathway + inhibitors will need to be combined with other drugs to be broadly effective. + We have employed genetically engineered mouse models that develop cancers + due to mutations in genes in the PI3K pathway and are using these models to + explore the efficacy of PI3K pathway inhibitors as single agents or in combination + with other drugs. We are also interrogating the role of PI3K in the growth + and survival of Brca1/p53 mutant breast cancers. The role of PI3K inhibitors + for treating cancers in these mouse models and in human trials will be discussed. + Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr MS1-1.", "venue": + "", "year": 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2012-12-15", "journal": {"volume": "72", "name": "Cancer Research"}, "authors": + [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2082997325", + "name": "C. Lewis"}]}, {"paperId": "2b1f8062ba70eb0c2c4bec6338f229cc28f5da51", + "externalIds": {"MAG": "2188400376", "CorpusId": 85632674}, "corpusId": 85632674, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/2b1f8062ba70eb0c2c4bec6338f229cc28f5da51", + "title": "Phosphoinositide 3- Kinase and disease", "abstract": null, "venue": + "", "year": 2012, "referenceCount": 2, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "10583217", "name": "W. Castle"}]}, {"paperId": + "4523700fc13dd617274e3215dee60ade51967111", "externalIds": {"MAG": "2094207365", + "DOI": "10.1038/nature10937", "CorpusId": 4307312, "PubMed": "22425996"}, + "corpusId": 4307312, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/4523700fc13dd617274e3215dee60ade51967111", + "title": "A murine lung cancer co-clinical trial identifies genetic modifiers + of therapeutic response", "abstract": null, "venue": "Nature", "year": 2012, + "referenceCount": 31, "citationCount": 429, "influentialCitationCount": 11, + "isOpenAccess": true, "openAccessPdf": {"url": "https://cdr.lib.unc.edu/downloads/8336h977p", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-03-29", "journal": {"volume": "483", "pages": "613-617", + "name": "Nature"}, "authors": [{"authorId": "1491946371", "name": "Zhao Chen"}, + {"authorId": "5719228", "name": "Katherine A. Cheng"}, {"authorId": "4440976", + "name": "Z. Walton"}, {"authorId": "2108898403", "name": "Yuchuan Wang"}, + {"authorId": "1899940", "name": "H. Ebi"}, {"authorId": "2882767", "name": + "T. Shimamura"}, {"authorId": "1700568", "name": "Yan Liu"}, {"authorId": + "3897844", "name": "T. Tupper"}, {"authorId": "153417190", "name": "J. Ouyang"}, + {"authorId": "2155868862", "name": "Jie Li"}, {"authorId": "144579867", "name": + "P. Gao"}, {"authorId": "49035877", "name": "M. S. Woo"}, {"authorId": "46747874", + "name": "Chunxiao Xu"}, {"authorId": "8500650", "name": "M. Yanagita"}, {"authorId": + "6594506", "name": "Abigail Altabef"}, {"authorId": "2108623086", "name": + "Shumei Wang"}, {"authorId": "2118593740", "name": "Charles Lee"}, {"authorId": + "3613098", "name": "Y. Nakada"}, {"authorId": "40050433", "name": "C. G. Pe\u00f1a"}, + {"authorId": "51240311", "name": "Yanping Sun"}, {"authorId": "4595444", "name": + "Yoko Franchetti"}, {"authorId": "50618836", "name": "C. Yao"}, {"authorId": + "8388167", "name": "A. Saur"}, {"authorId": "1906844", "name": "M. Cameron"}, + {"authorId": "34983104", "name": "M. Nishino"}, {"authorId": "143731085", + "name": "D. Hayes"}, {"authorId": "145818770", "name": "M. Wilkerson"}, {"authorId": + "36745098", "name": "P. Roberts"}, {"authorId": "153897222", "name": "Carrie + Lee"}, {"authorId": "5974412", "name": "N. Bardeesy"}, {"authorId": "5775728", + "name": "M. Butaney"}, {"authorId": "6510669", "name": "L. Chirieac"}, {"authorId": + "47104850", "name": "D. Costa"}, {"authorId": "1904539", "name": "D. Jackman"}, + {"authorId": "3525978", "name": "N. Sharpless"}, {"authorId": "4565019", "name": + "D. Castrillon"}, {"authorId": "4026228", "name": "G. Demetri"}, {"authorId": + "5984202", "name": "P. J\u00e4nne"}, {"authorId": "4499580", "name": "P. Pandolfi"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145326814", "name": + "A. Kung"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "32596484", + "name": "Kwok-Kin Wong"}]}, {"paperId": "4c4b0282f39b3f1211974e0e9cc65f8dbc84c369", + "externalIds": {"MAG": "1986186950", "DOI": "10.1002/jcp.22895", "CorpusId": + 20585236, "PubMed": "21688263"}, "corpusId": 20585236, "publicationVenue": + {"id": "cdf4bb1c-e624-482e-8289-da2009c4c31a", "name": "Journal of Cellular + Physiology", "type": "journal", "alternate_names": ["J Cell Physiol"], "issn": + "0021-9541", "url": "http://eu.wiley.com/WileyCDA/WileyTitle/productCd-JCP.html", + "alternate_urls": ["http://www3.interscience.wiley.com/cgi-bin/jhome/109898032", + "http://onlinelibrary.wiley.com/journal/10.1002/%28issn%291097-4652", "http://onlinelibrary.wiley.com/journal/10.1002/(issn)1097-4652", + "https://onlinelibrary.wiley.com/journal/10974652", "http://www3.interscience.wiley.com/cgi-bin/jhome/31010"]}, + "url": "https://www.semanticscholar.org/paper/4c4b0282f39b3f1211974e0e9cc65f8dbc84c369", + "title": "Inhibition of lung cancer growth: ATP citrate lyase knockdown and + statin treatment leads to dual blockade of mitogen\u2010activated protein + Kinase (MAPK) and Phosphatidylinositol\u20103\u2010kinase (PI3K)/AKT pathways", + "abstract": "ATP citrate lyase (ACL) catalyzes the conversion of cytosolic + citrate to acetyl\u2010CoA and oxaloacetate. A definitive role for ACL in + tumorigenesis has emerged from ACL RNAi and chemical inhibitor studies, showing + that ACL inhibition limits tumor cell proliferation and survival and induces + differentiation in vitro. In vivo, it reduces tumor growth leading to a cytostatic + effect and induces differentiation. However, the underlying molecular mechanisms + are poorly understood and agents that could enhance the efficacy of ACL inhibition + have not been identified. Our studies focus on non\u2010small cell lung cancer + (NSCLC) lines, which show phosphatidylinositol 3\u2010kinase (PI3K)/AKT activation + secondary to a mutation in the K\u2010Ras gene or the EGFR gene. Here we show + that ACL knockdown promotes apoptosis and differentiation, leading to the + inhibition of tumor growth in vivo. Moreover, in contrast to most studies, + which elucidate how activation/suppression of signaling pathways can modify + metabolism, we show that inhibition of a metabolic pathway \u201creverse signals\u201d + and attenuates PI3K/AKT signaling. Additionally, we find that statins, inhibitors + of 3\u2010hydroxy\u20103\u2010methylglutaryl coenzyme A (HMG\u2010CoA) reductase, + which act downstream of ACL in the cholesterol synthesis pathway, dramatically + enhance the anti\u2010tumor effects of ACL inhibition, even regressing established + tumors. With statin treatment, both PI3K/AKT and the MAPK pathways are affected. + Moreover, this combined treatment is able to reduce the growth of EGF receptor + resistant tumor cell types. Given the essential role of lipid synthesis in + numerous cancers, this work may impact therapy in a broad range of tumors. + J. Cell. Physiol. 227: 1709\u20131720, 2012. \u00a9 2011 Wiley Periodicals, + Inc.", "venue": "Journal of Cellular Physiology", "year": 2012, "referenceCount": + 69, "citationCount": 133, "influentialCitationCount": 5, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3407542?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-04-01", "journal": {"volume": "227", "name": "Journal + of Cellular Physiology"}, "authors": [{"authorId": "4394032", "name": "J. + Hanai"}, {"authorId": "4596169", "name": "N. Doro"}, {"authorId": "47742211", + "name": "A. Sasaki"}, {"authorId": "2109836647", "name": "S. Kobayashi"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "143667851", "name": + "P. Seth"}, {"authorId": "3658233", "name": "V. Sukhatme"}]}, {"paperId": + "52652858006f5dd5120b9dc50eafd52697a8c723", "externalIds": {"MAG": "2093644658", + "DOI": "10.1016/j.cmet.2012.05.010", "CorpusId": 206839490, "PubMed": "22727014"}, + "corpusId": 206839490, "publicationVenue": {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", + "name": "Cell Metabolism", "type": "journal", "alternate_names": ["Cell Metab"], + "issn": "1550-4131", "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/15504131", "http://www.cellmetabolism.org/"]}, + "url": "https://www.semanticscholar.org/paper/52652858006f5dd5120b9dc50eafd52697a8c723", + "title": "p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin''s + effect on food intake.", "abstract": null, "venue": "Cell Metabolism", "year": + 2012, "referenceCount": 40, "citationCount": 225, "influentialCitationCount": + 18, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1550413112002331/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2012-07-03", "journal": {"volume": + "16 1", "pages": "\n 104-12\n ", "name": "Cell metabolism"}, + "authors": [{"authorId": "3734143", "name": "Y. Dagon"}, {"authorId": "4874129", + "name": "E. Hur"}, {"authorId": "143918840", "name": "B. Zheng"}, {"authorId": + "4673484", "name": "Kerry Wellenstein"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "1997179", "name": "B. Kahn"}]}, {"paperId": "597475f86bbe11151cac521cf1a6c46a745db69b", + "externalIds": {"MAG": "2277249887", "CorpusId": 87310081}, "corpusId": 87310081, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/597475f86bbe11151cac521cf1a6c46a745db69b", + "title": "Pyruvate kinase M2 deficiency promotes a brown fat-like program + in white adipocytes", "abstract": null, "venue": "", "year": 2012, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "5956178", + "name": "Ahmed Bettaieb"}, {"authorId": "50186862", "name": "Jesse L Bakke"}, + {"authorId": "3957054", "name": "N. Nagata"}, {"authorId": "35252324", "name": + "A. Tomilov"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "3560122", "name": "G. Cortopassi"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5546228", "name": + "F. Haj"}]}, {"paperId": "5b132427312e64747dfc4fcb7b10d9535069626d", "externalIds": + {"MAG": "2105685115", "DOI": "10.1016/j.cell.2012.02.030", "CorpusId": 14246515, + "PubMed": "22401813"}, "corpusId": 14246515, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/5b132427312e64747dfc4fcb7b10d9535069626d", + "title": "Systemic Elevation of PTEN Induces a Tumor-Suppressive Metabolic + State", "abstract": null, "venue": "Cell", "year": 2012, "referenceCount": + 94, "citationCount": 341, "influentialCitationCount": 10, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867412002309/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2012-03-30", "journal": {"volume": + "149", "pages": "49-62", "name": "Cell"}, "authors": [{"authorId": "1402741417", + "name": "I. Garcia-Cao"}, {"authorId": "2967391", "name": "M. Song"}, {"authorId": + "4584039", "name": "R. Hobbs"}, {"authorId": "3543087", "name": "Gaelle Laurent"}, + {"authorId": "3571606", "name": "C. Giorgi"}, {"authorId": "40052947", "name": + "V. D. Boer"}, {"authorId": "46996935", "name": "D. Anastasiou"}, {"authorId": + "143651419", "name": "Keisuke Ito"}, {"authorId": "47742211", "name": "A. + Sasaki"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": "6988610", + "name": "A. Carracedo"}, {"authorId": "35413264", "name": "M. V. Heiden"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3936492", "name": + "P. Pinton"}, {"authorId": "6212141", "name": "M. Haigis"}, {"authorId": "4499580", + "name": "P. Pandolfi"}]}, {"paperId": "5b1d2d3d01e2fa53506a9e048d1874acf5f5c3ce", + "externalIds": {"MAG": "2157066764", "DOI": "10.1016/j.chembiol.2012.07.021", + "CorpusId": 10040118, "PubMed": "22999886"}, "corpusId": 10040118, "publicationVenue": + {"id": "0c73784e-4058-48ce-b429-740c11d6f005", "name": "Chemistry and Biology", + "type": "journal", "alternate_names": ["Chemistry & Biology", "Chem Biology", + "Chem Biology"], "issn": "1074-5521", "alternate_issns": ["1879-1301"], "url": + "http://www.chembiol.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/10745521", + "https://www.journals.elsevier.com/chemistry-and-biology"]}, "url": "https://www.semanticscholar.org/paper/5b1d2d3d01e2fa53506a9e048d1874acf5f5c3ce", + "title": "Small molecule activation of PKM2 in cancer cells induces serine + auxotrophy.", "abstract": null, "venue": "Chemistry and Biology", "year": + 2012, "referenceCount": 52, "citationCount": 147, "influentialCitationCount": + 4, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry", "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2012-09-01", "journal": + {"volume": "19 9", "pages": "\n 1187-98\n ", "name": "Chemistry + & biology"}, "authors": [{"authorId": "7636232", "name": "C. Kung"}, {"authorId": + "39459677", "name": "J. Hixon"}, {"authorId": "47406687", "name": "S. Choe"}, + {"authorId": "145638995", "name": "K. Marks"}, {"authorId": "144707828", "name": + "S. Gross"}, {"authorId": "2056227217", "name": "Erin Murphy"}, {"authorId": + "49437145", "name": "B. Delabarre"}, {"authorId": "3662288", "name": "Giovanni + Cianchetta"}, {"authorId": "5222482", "name": "Shalini Sethumadhavan"}, {"authorId": + "2144657971", "name": "Xiling Wang"}, {"authorId": "34156476", "name": "Shunqi + Yan"}, {"authorId": "2118543810", "name": "Yi Gao"}, {"authorId": "144655992", + "name": "Cheng Fang"}, {"authorId": "50770525", "name": "Wentao Wei"}, {"authorId": + "2069982648", "name": "F. Jiang"}, {"authorId": "2145317633", "name": "Shaohui + Wang"}, {"authorId": "4136146", "name": "K. Qian"}, {"authorId": "144512128", + "name": "J. Saunders"}, {"authorId": "4691854", "name": "E. Driggers"}, {"authorId": + "40582612", "name": "H. Woo"}, {"authorId": "8330889", "name": "K. Kunii"}, + {"authorId": "39549437", "name": "Stuart Murray"}, {"authorId": "11325796", + "name": "Hua Yang"}, {"authorId": "4886372", "name": "K. Yen"}, {"authorId": + "1722649", "name": "Wei Liu"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3804233", "name": "M. V. Vander Heiden"}, {"authorId": "4297092", + "name": "S. Su"}, {"authorId": "5210229", "name": "Shengfang Jin"}, {"authorId": + "5908187", "name": "F. Salituro"}, {"authorId": "38799894", "name": "L. Dang"}]}, + {"paperId": "5bae21d441b729d1c4b9f9a2137ba8c5d747b1b3", "externalIds": {"MAG": + "2014040910", "DOI": "10.1158/1538-7445.PANCA2012-IA14", "CorpusId": 84282341}, + "corpusId": 84282341, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/5bae21d441b729d1c4b9f9a2137ba8c5d747b1b3", + "title": "Abstract IA14: Autophagy, metabolism, and pancreatic cancer.", "abstract": + "Pancreatic cancers have an intense resistance to currently available therapeutics + which results in a dismal 5-year survival rate. This resistance points toward + altered cell survival and metabolic pathways. In this regard we have previously + shown that pancreatic cancers have elevated basal autophagy, which is required + for their continued growth. Importantly, inhibition of autophagy pharmacologically + or by RNAi approaches leads to decreased oxidative phosphorylation, a drop + in ATP production, and ultimately growth inhibition. These findings have implicated + autophagy as a key component of pancreatic cancer metabolism and have motivated + the opening of multiple clinical trials assessing the efficacy of hydroxychloroquine + as an autophagy inhibitor in pancreatic cancer. Additional work from our group + has demonstrated that oncogenic Kras promotes a systematic rewiring of pancreatic + cancer metabolism allowing glucose and glutamine to be utilized in a variety + of biosynthetic pathways. Importantly, several of these metabolic pathways + are critical for tumor growth and therefore represent potential therapeutic + targets. These and other aspects of pancreatic cancer metabolism will be discussed.\n\nCitation + Format: Jaekyoung Son, Costas A. Lyssiotis, Shenghong Yang, Haoqiang Ying, + Xiaoxu Wang, Lewis C. Cantley, Alec C. Kimmelman. Autophagy, metabolism, and + pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference + on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, + NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr IA14.", + "venue": "", "year": 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2012-07-15", "journal": {"volume": "72", "name": "Cancer Research"}, "authors": + [{"authorId": "38313825", "name": "J. Son"}, {"authorId": "4901222", "name": + "C. Lyssiotis"}, {"authorId": "50591635", "name": "Shenghong Yang"}, {"authorId": + "33312849", "name": "H. Ying"}, {"authorId": "48631933", "name": "Xiaoxu Wang"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4668673", "name": + "A. Kimmelman"}]}, {"paperId": "5bec7aef76f7550061a5440b5a306ad5d505c112", + "externalIds": {"MAG": "2044098634", "DOI": "10.1038/cr.2012.5", "CorpusId": + 10626336, "PubMed": "22212478"}, "corpusId": 10626336, "publicationVenue": + {"id": "45c77f4e-d4c0-4df3-99dd-119b0d2adb78", "name": "Cell Research", "type": + "journal", "alternate_names": ["Cell Res"], "issn": "1001-0602", "url": "http://www.cell-research.com/", + "alternate_urls": ["http://www.cell-research.com/index.asp", "http://www.nature.com/cr/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/5bec7aef76f7550061a5440b5a306ad5d505c112", + "title": "Breathless cancer cells get fat on glutamine", "abstract": null, + "venue": "Cell Research", "year": 2012, "referenceCount": 14, "citationCount": + 61, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/cr20125.pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2012-03-01", "journal": {"volume": "22", "pages": "443-446", "name": "Cell + Research"}, "authors": [{"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "61830267754adefd87a2c3f3cd7f518f1e2bb524", + "externalIds": {"PubMedCentral": "3511602", "MAG": "1969836970", "DOI": "10.1038/ncb2629", + "CorpusId": 11331744}, "corpusId": 11331744, "publicationVenue": {"id": "7d182b83-7d8d-43fb-9fd6-ae67fbafab20", + "name": "Nature Cell Biology", "type": "journal", "alternate_names": ["Nat + Cell Biology"], "issn": "1465-7392", "url": "http://www.nature.com/naturecellbiology", + "alternate_urls": ["https://www.nature.com/ncb/"]}, "url": "https://www.semanticscholar.org/paper/61830267754adefd87a2c3f3cd7f518f1e2bb524", + "title": "ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 + promotes the Warburg effect", "abstract": null, "venue": "Nature Cell Biology", + "year": 2012, "referenceCount": 33, "citationCount": 392, "influentialCitationCount": + 31, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3511602?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2012-11-05", "journal": {"volume": + "14", "pages": "1295 - 1304", "name": "Nature cell biology"}, "authors": [{"authorId": + "143956168", "name": "Weiwei Yang"}, {"authorId": "3169180", "name": "Yanhua + Zheng"}, {"authorId": "143733371", "name": "Yan Xia"}, {"authorId": "2579875", + "name": "Haitao Ji"}, {"authorId": "48283607", "name": "Xiaomin Chen"}, {"authorId": + "152831013", "name": "F. Guo"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "50138848", "name": "K. Aldape"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "5467266", "name": "Zhimin Lu"}]}, {"paperId": + "69c60c9edc44b999870d3bfe7c18fd34dc835973", "externalIds": {"MAG": "2044216772", + "DOI": "10.1016/j.cell.2012.11.020", "CorpusId": 691118, "PubMed": "23217699"}, + "corpusId": 691118, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/69c60c9edc44b999870d3bfe7c18fd34dc835973", + "title": "SIRT6 Puts Cancer Metabolism in the Driver\u2019s Seat", "abstract": + null, "venue": "Cell", "year": 2012, "referenceCount": 14, "citationCount": + 25, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867412014055/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", "LettersAndComments"], + "publicationDate": "2012-12-07", "journal": {"volume": "151", "pages": "1155-1156", + "name": "Cell"}, "authors": [{"authorId": "4901222", "name": "C. Lyssiotis"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "6c972bad36661b430cf345e70b4601769815c17f", + "externalIds": {"MAG": "2077776680", "DOI": "10.1158/1538-7445.AM2012-LB-365", + "CorpusId": 72871432}, "corpusId": 72871432, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/6c972bad36661b430cf345e70b4601769815c17f", + "title": "Abstract LB-365: Effective use of PI3K/MTOR and MEK inhibitors prior + to hormone ablative therapy in PTEN-loss driven murine prostate cancer", "abstract": + "Proceedings: AACR 103rd Annual Meeting 2012\u2010\u2010 Mar 31\u2010Apr 4, + 2012; Chicago, IL\n\nThe PTEN and p53 tumor suppressors are the most commonly + altered genes in human cancer, including prostate cancer (PCa). Loss of PTEN + is associated with increased Gleason score and clinical recurrence, and the + majority of human metastatic PCas have PTEN loss via multiple mechanisms. + Mice with prostate-specific homozygous deletion of PTEN develop invasive PCa + albeit with prolonged latency of 6-8 months. Combined PTEN/p53 inactivation + in mouse prostate elicits invasive cancer by 9 weeks of age and invariable + lethality by 6 months of age. Since PTEN loss results in PI3K/mTOR pathway + activation, we evaluated the impact of GSK458 (PI3K/mTOR inhibitor) and GSK418 + (PI3K beta/delta isoform-specific inhibitor), singly and in combination with + GSK212 (MEK inhibitor), in uncastrated, prostate-specific PTEN/p53 double + knockout mice (4-6 months) and PTEN mice (11-14 months), respectively, harboring + advanced PCa. The drugs were administered by daily oral gavage for 3 weeks + with serial 18FDG-PET/MRI imaging at baseline, 2 days, 1 week, 2 weeks and + 3 weeks post-treatment respectively. GSK458 treatment of PTEN/p53 and PTEN + mice results in reduction in FDG-PET uptake as early as 24 h post-treatment, + with 40% tumor shrinkage by 1 week post-treatment, but rapid regrowth of 18FDG-avid + tumor by 2-3 weeks post-treatment. This acquired resistance was found to be + mediated in part through upregulation of multiple receptor tyrosine kinases. + In contrast, PTEN/p53 and PTEN mice did not respond to GSK418, by either FDG-PET + or MRI analysis. We observed increased pERK/total ERK ratio by Western blot + analysis and increased p-ERK staining by immunohistochemistry in GSK458 and + GSK418-treated PTEN/53 mice, respectively. Treatment of PTEN/p53 and PTEN + mice with GSK212 resulted in an approx. 40% reduction in tumor volume over + 3 weeks. Treatment of PTEN/p53 mice with a combination of GSK458 plus GSK212 + resulted in approx. 60% reduction of tumor volume at 3 week post-treatment. + Strikingly, treatment of prostate-specific PTEN only mice with GSK458 plus + GSK212 combination resulted in a >90% tumor regression at 3 weeks post-treatment. + These results demonstrate the potential utlitity of PI3K/MEK-directed combination + therapies in the neoadjuvant setting for locally advanced disease or hormone-sensitive + phase in metastatic disease, thus delaying the need for hormone ablative therapy + and its associated morbidity in advanced PCa. The data underscore the value + of genetically engineered mouse models to co-clinically evaluate biomarkers + of response and resistance to targeted therapies, and elucidate mechanisms + of acquired resistance early in clinical development. The design of \u201cpersonalized\u201d + combination therapies to overcome resistance to PI3K/MEK-directed therapies + in the hormone-naive and castration-resistant contexts are currently underway + in multiple GEMMs and Phase Ib co-clinical trials in advanced PCa.\n\nCitation + Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd + Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr + 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract + nr LB-365. doi:1538-7445.AM2012-LB-365", "venue": "", "year": 2012, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2012-04-15", "journal": {"volume": "72", "name": "Cancer + Research"}, "authors": [{"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "13782167", "name": "K. Courtney"}, {"authorId": "40638403", "name": "K. Robichaud"}, + {"authorId": "5679020", "name": "G. Bellinger"}, {"authorId": "3547827", "name": + "C. Nardella"}, {"authorId": "7505152", "name": "S. Signoretti"}, {"authorId": + "46825918", "name": "R. Wooster"}, {"authorId": "4499580", "name": "P. Pandolfi"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "70550699ba9c5f4a62ab0e5c454cdaf99bf4b6c3", + "externalIds": {"MAG": "2102759054", "DOI": "10.1158/2159-8290.CD-11-0327", + "CorpusId": 37975989, "PubMed": "22585178"}, "corpusId": 37975989, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/70550699ba9c5f4a62ab0e5c454cdaf99bf4b6c3", + "title": "Cancer Discovery at one year: the editors'' interim analysis.", + "abstract": "Our interim analysis is strikingly positive as Cancer Discovery + enters into its second year, and we hope the journal will become an increasingly + indispensable resource to both basic and clinical cancer researchers.\n\n![Figure][1] + \n\nAs Cancer Discovery approaches its first anniversary, we would like to + share with you our initial assessment of the life and health of this young + journal of the American Association for Cancer Research (AACR). If we were + to analyze the journal in a similar fashion as would be done with a clinical + trial for a new and exciting compound, we would call this a prespecified interim + analysis, also known as an \u201cearly look.\u201d Early looks are by nature + tricky. If the findings are positive but do not cross a given boundary, they + could simply be false-positive. However, if they are negative to begin with, + this does not mean that the study results will be negative after more prolonged + follow-up.\n\nFirst, let us look at the Methods of the journal. The concept + behind Cancer Discovery was, and is, to be a \u2026\n\n [1]: pending:yes", + "venue": "Cancer Discovery", "year": 2012, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["Editorial"], + "publicationDate": null, "journal": {"volume": "2 1", "pages": "\n vi\n ", + "name": "Cancer discovery"}, "authors": [{"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "144806171", "name": "J. Baselga"}]}, {"paperId": + "73fdd0d7ac12e636d4f82e1a090e73b3c6c53466", "externalIds": {"PubMedCentral": + "3711671", "MAG": "2125836344", "DOI": "10.1038/nchembio.1060", "CorpusId": + 1641001, "PubMed": "22922757"}, "corpusId": 1641001, "publicationVenue": {"id": + "7758f686-2a47-473d-835c-6784e70a0aac", "name": "Nature Chemical Biology", + "type": "journal", "alternate_names": ["Nat Chem Biology"], "issn": "1552-4450", + "url": "https://www.nature.com/nchembio/", "alternate_urls": ["http://www.nature.com/nchembio/index.html"]}, + "url": "https://www.semanticscholar.org/paper/73fdd0d7ac12e636d4f82e1a090e73b3c6c53466", + "title": "Pyruvate kinase M2 activators promote tetramer formation and suppress + tumorigenesis", "abstract": null, "venue": "Nature Chemical Biology", "year": + 2012, "referenceCount": 61, "citationCount": 609, "influentialCitationCount": + 32, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3711671?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-09-07", "journal": {"volume": "8", "pages": "839 + - 847", "name": "Nature chemical biology"}, "authors": [{"authorId": "46996935", + "name": "D. Anastasiou"}, {"authorId": "1924735", "name": "Yimin Yu"}, {"authorId": + "5553029", "name": "W. J. Israelsen"}, {"authorId": "4084746", "name": "Jian-Kang + Jiang"}, {"authorId": "3275486", "name": "M. Boxer"}, {"authorId": "6351971", + "name": "B. Hong"}, {"authorId": "5566934", "name": "W. Tempel"}, {"authorId": + "33892021", "name": "S. Dimov"}, {"authorId": "145829790", "name": "M. Shen"}, + {"authorId": "38884428", "name": "Abhishek Jha"}, {"authorId": "47912756", + "name": "Hua Yang"}, {"authorId": "6160202", "name": "K. Mattaini"}, {"authorId": + "2281284", "name": "C. Metallo"}, {"authorId": "8143199", "name": "B. Fiske"}, + {"authorId": "13782167", "name": "K. Courtney"}, {"authorId": "3870192", "name": + "S. Malstrom"}, {"authorId": "47670281", "name": "Tahsin M. Khan"}, {"authorId": + "7636232", "name": "C. Kung"}, {"authorId": "5914392", "name": "A. P. Skoumbourdis"}, + {"authorId": "1799343", "name": "H. Veith"}, {"authorId": "49134285", "name": + "Noel Southall"}, {"authorId": "1699620778", "name": "M. Walsh"}, {"authorId": + "2435894", "name": "K. Brimacombe"}, {"authorId": "3802281", "name": "W. Leister"}, + {"authorId": "39089704", "name": "S. Lunt"}, {"authorId": "51164649", "name": + "Zachary R. Johnson"}, {"authorId": "4886372", "name": "K. Yen"}, {"authorId": + "8330889", "name": "K. Kunii"}, {"authorId": "34711277", "name": "Shawn M. + Davidson"}, {"authorId": "4164415", "name": "H. Christofk"}, {"authorId": + "4066869", "name": "C. Austin"}, {"authorId": "3155966", "name": "James Inglese"}, + {"authorId": "2087058005", "name": "M. H. Harris"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}, + {"authorId": "5908187", "name": "F. Salituro"}, {"authorId": "5210229", "name": + "Shengfang Jin"}, {"authorId": "38799894", "name": "L. Dang"}, {"authorId": + "2607088", "name": "D. Auld"}, {"authorId": "2790262", "name": "Hee-won Park"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2148769632", + "name": "Craig J. Thomas"}, {"authorId": "3804233", "name": "M. V. Vander + Heiden"}]}, {"paperId": "787ea424b3f71b4642cb445dbf50347431c988e4", "externalIds": + {"MAG": "2941638450", "CorpusId": 5166233}, "corpusId": 5166233, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/787ea424b3f71b4642cb445dbf50347431c988e4", + "title": "Anastasiou Contributes to Cellular Antioxidant Responses Inhibition + of Pyruvate Kinase M 2 by Reactive Oxygen Species", "abstract": "clicking + here. colleagues, clients, or customers by , you can order high-quality copies + for your If you wish to distribute this article to others here. following + the guidelines can be obtained by Permission to republish or repurpose articles + or portions of articles ): October 5, 2012 www.sciencemag.org (this information + is current as of The following resources related to this article are available + online at", "venue": "", "year": 2012, "referenceCount": 40, "citationCount": + 12, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "name": ""}, "authors": [{"authorId": "46996935", "name": "D. Anastasiou"}, + {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "3275486", "name": "M. Boxer"}, {"authorId": + "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "145829790", "name": "M. + Shen"}, {"authorId": "5679020", "name": "G. Bellinger"}, {"authorId": "47742211", + "name": "A. Sasaki"}, {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "2607088", "name": "D. Auld"}, {"authorId": "2149108162", "name": "C. Thomas"}, + {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "79bc07989e16c7b180f40211aa48c8f4fe317cf2", + "externalIds": {"MAG": "1971439437", "DOI": "10.1093/ANNONC/MDS366", "CorpusId": + 70477380}, "corpusId": 70477380, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/79bc07989e16c7b180f40211aa48c8f4fe317cf2", + "title": "PI 3\u2014kinase and cancer metabolism", "abstract": "ABSTRACT Phosphoinositide + 3-kinase (PI 3-Kinase) generates phosphatidylinositol-3,4,5-trisphosphate + (PIP3) at the plasma membrane in response to stimulation of cells with growth + factors and hormones. This lipid recruits certain signal transduction proteins + to the membrane, initializing cellular signaling cascades that control glucose + uptake, cell metabolism, protein synthesis and cell growth. A central mediator + of PI 3-Kinase signaling is the protein-Ser/Thr kinase, AKT. Over the past + six years signaling networks downstream of AKT have been elucidated that regulate + protein synthesis and glucose metabolism, in part via activation of mTOR. + Importantly, we have found that while growth factor receptors enhance glucose + uptake and glucose metabolism, they decrease the activity of pyruvate kinase, + the last step in the pathway. Our studies indicate that the inhibition of + pyruvate kinase allows cells to divert intermediates in glycolysis into pathways + for synthesis of DNA, RNA, proteins and lipids that are needed for cell growth. + Disclosure Dr. Cantley is a founder and member of the BOD of Agios Pharmaceuticals, + a company that targets metabolic enzymes for treating cancer. Dr. Cantley + consults for Novartis and GSK, companies developing drugs that target PI3K.", + "venue": "", "year": 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2012-09-01", + "journal": {"volume": "23", "name": "Annals of Oncology"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "7a2160312ce89614d09c94de20d857464bcfaaa7", + "externalIds": {"MAG": "2120806256", "DOI": "10.1158/2159-8290.CD-11-0336", + "CorpusId": 9389722, "PubMed": "22915751"}, "corpusId": 9389722, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/7a2160312ce89614d09c94de20d857464bcfaaa7", + "title": "Combining a PI3K inhibitor with a PARP inhibitor provides an effective + therapy for BRCA1-related breast cancer.", "abstract": "UNLABELLED\nThere + is a need to improve treatments for metastatic breast cancer. Here, we show + the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated + protein kinase (MAPK) pathways in a MMTV-CreBrca1(f/f)Trp53(+/-) mouse model + of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, + tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, + tumor cell proliferation, and angiogenesis. Resistant tumors maintained suppression + of AKT phosphorylation but exhibited activation of the MAPK pathway at the + \"pushing margin.\" Surprisingly, PI3K inhibition increased indicators of + DNA damage, poly-ADP-ribosylation (PAR), and \u03b3-H2AX, but decreased Rad51 + focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. + The PARP inhibitor olaparib alone attenuated tumor growth modestly; however, + the combination of NVP-BKM120 and olaparib delayed tumor doubling to more + than 70 days in the mouse model and more than 50 days in xenotransplants from + human BRCA1-related tumors, suggesting that combined PI3K and PARP inhibition + might be an effective treatment of BRCA1-related tumors.\n\n\nSIGNIFICANCE\nCurrent + treatment options for triple-negative breast cancer are limited to chemotherapeutic + regimens that have considerable toxicity and are not curative. We report here + that the combination of a PI3K inhibitor with a PARP inhibitor provides in + vivo synergy for treatment of an endogenous mouse model for BRCA1-related + breast cancers, making this a candidate combination to be tested in human + clinical trials.", "venue": "Cancer Discovery", "year": 2012, "referenceCount": + 65, "citationCount": 374, "influentialCitationCount": 8, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3733368?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-11-01", "journal": {"volume": "2 11", "pages": "\n 1048-63\n ", + "name": "Cancer discovery"}, "authors": [{"authorId": "49149990", "name": + "Ashish Juvekar"}, {"authorId": "48793812", "name": "L. Burga"}, {"authorId": + "2108652866", "name": "Hai Hu"}, {"authorId": "3772950", "name": "E. Lunsford"}, + {"authorId": "2822826", "name": "Y. Ibrahim"}, {"authorId": "4568053", "name": + "J. Balma\u00f1a"}, {"authorId": "5146712", "name": "Anbazhagan Rajendran"}, + {"authorId": "5380009", "name": "A. Papa"}, {"authorId": "2060529577", "name": + "Katherine Spencer"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": + "3547827", "name": "C. Nardella"}, {"authorId": "4499580", "name": "P. Pandolfi"}, + {"authorId": "144806171", "name": "J. Baselga"}, {"authorId": "143905392", + "name": "R. Scully"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "31554501", "name": "G. Wulf"}]}, + {"paperId": "82851aec21dab1cf1a444bcfa4bed5b88eeba0f6", "externalIds": {"MAG": + "2328336876", "DOI": "10.1158/1538-7445.AM2012-LB-161", "CorpusId": 75837891}, + "corpusId": 75837891, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/82851aec21dab1cf1a444bcfa4bed5b88eeba0f6", + "title": "Abstract LB-161: Metformin increases lipolytic metabolism and PEDF + expression in prostate cancer cells", "abstract": "Obesity increases the risk + of prostate cancer (PCa) progression; however, the mechanism remains unclear. + Obesity results in metabolic dysfunction, including increases in circulating + and tissue lipid levels. A common sequela of obesity is Type II diabetes, + and some studies suggest that PCa patients on the antidiabetic drug, metformin, + have a reduced PCa risk. The antitumor mechanism of metformin is largely unknown. + Metformin exerts its antidiabetic function via AMPK activation-dependent inhibition + of hepatic gluconeogenesis, with secondary decrease in serum insulin/IGF-1 + levels that may represent an indirect mechanism for its proposed antitumor + effects. Previous studies have shown that metformin directly inhibits PCa + cell proliferation and cyclin D1 expression in vitro. Expression of pigment + epithelium-derived factor (PEDF), a potent angiogenesis inhibitor, is decreased + in PCa tissues, and PEDF inhibits PCa cell proliferation. Interestingly, PEDF + knockout mice have defects in lipid metabolism and develop prostate hyperplasia, + so we hypothesized that metformin9s antitumor mechanism could be mediated, + in part, through regulation of PEDF expression and lipolytic metabolism. To + simulate obesity-induced cellular triglyceride (TG) accumulation, we treated + cells with oleic acid (OA, 1.0 mM) \u00b1 PEDF (10 nM) or metformin (5 mM). + Proliferation (cell count or MTT assay) and lipid content (TG isolation) were + quantified, and lipid and protein were assessed by lipid staining and immunocytochemistry + or Western blot, respectively. In androgen-insensitive PCa cells (PC-3 and + DU145), OA treatment promoted TG accumulation, cyclin D1 expression and proliferation, + with increased expression of lipid droplet-associated proteins, adipose triglyceride + lipase (ATGL) and CGI-58, and conversely suppressed PEDF expression. Furthermore, + PEDF treatment decreased basal TG levels (32.89 \u00b1 1.0 control vs. 17.3 + \u00b1 0.6 in PEDF; P Citation Format: {Authors}. {Abstract title} [abstract]. + In: Proceedings of the 103rd Annual Meeting of the American Association for + Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; + Cancer Res 2012;72(8 Suppl):Abstract nr LB-161. doi:1538-7445.AM2012-LB-161", + "venue": "", "year": 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2012-04-15", "journal": {"volume": + "72", "name": "Cancer Research"}, "authors": [{"authorId": "40501341", "name": + "A. Patnaik"}, {"authorId": "14331821", "name": "Susan M. Wcislak"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5369007", "name": "J. Doll"}]}, + {"paperId": "84be76f1b8732bdcc7c89b455a8191c9ed3ad03e", "externalIds": {"MAG": + "2144535296", "PubMedCentral": "3255319", "DOI": "10.3410/B4-2", "CorpusId": + 15640245, "PubMed": "22242042"}, "corpusId": 15640245, "publicationVenue": + {"id": "98d0f85f-e67d-4612-99a0-ab577ada6952", "name": "F1000 Biology Reports", + "alternate_names": ["F1000 Biology Rep"], "issn": "1757-594X", "url": "https://f1000.com/prime/reports/browse", + "alternate_urls": ["http://www.f1000biology.com/reports"]}, "url": "https://www.semanticscholar.org/paper/84be76f1b8732bdcc7c89b455a8191c9ed3ad03e", + "title": "Decoding key nodes in the metabolism of cancer cells: sugar & spice + and all things nice", "abstract": "In the past 5 years, a convergence of studies + has resulted in a broad appreciation in the cancer research community that + reprogramming of cellular metabolism may be more central to cancer than appreciated + in the past 30 years. The re-emergence of cancer metabolism stems in part + from discoveries that a number of common oncogenes and tumor suppressor genes + more directly control cell metabolism than previously thought. In addition, + a number of what would previously have been called \u201ccard-carrying\u201d + metabolic enzymes have been identified as human tumor suppressors or oncogenes, + causally mutated in a variety of human cancers. This growing appreciation + of the role of altered cell metabolism has led to further investigation into + the rate-limiting proteins involved in different aspects of the unique metabolism + of tumor cells. Targeting cancer metabolism with drugs requires a therapeutic + window in which tumor cells, compared to normal tissues, have a greater dependence + on specific metabolic enzymes. Themes that have emerged in the past decade + of developing oncogene-targeted cancer therapeutics suggest that tumors with + distinct oncogenic lesions are likely to require drugs that target distinct + metabolic pathways. Ultimately, the hope is that detailed knowledge of oncogene + and tumor suppressor gene functions and their effects on metabolism will lead + to drug combinations that will be far more effective in treating cancers.", + "venue": "F1000 Biology Reports", "year": 2012, "referenceCount": 38, "citationCount": + 32, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://facultyopinions.com/prime/reports/b/4/2/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2012-01-03", "journal": {"volume": "4", "name": "F1000 Biology Reports"}, + "authors": [{"authorId": "4426388", "name": "R. Shaw"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "8c8926d0a6362ce565dba210fbb47c91d17b0102", + "externalIds": {"MAG": "1998709192", "DOI": "10.1016/j.molcel.2012.01.010", + "CorpusId": 22323222, "PubMed": "22342344"}, "corpusId": 22323222, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/8c8926d0a6362ce565dba210fbb47c91d17b0102", + "title": "p85\u03b1 SH2 domain phosphorylation by IKK promotes feedback inhibition + of PI3K and Akt in response to cellular starvation.", "abstract": null, "venue": + "Molecules and Cells", "year": 2012, "referenceCount": 45, "citationCount": + 66, "influentialCitationCount": 6, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1097276512000524/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-03-30", "journal": {"volume": "45 6", "pages": "\n 719-30\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "4037235", "name": "W. + Comb"}, {"authorId": "6742227", "name": "Jessica E. Hutti"}, {"authorId": + "6606210", "name": "P. Cogswell"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2157007", "name": "A. Baldwin"}]}, {"paperId": "906ec648aab69f9f823e672efcffd7f06ca3f361", + "externalIds": {"MAG": "2102188028", "DOI": "10.1093/jmcb/mjr030", "CorpusId": + 11591143, "PubMed": "22044881"}, "corpusId": 11591143, "publicationVenue": + {"id": "f5508b8f-47ff-42d2-9d7e-6296f3bb46a2", "name": "Journal of Molecular + Cell Biology", "type": "journal", "alternate_names": ["J Mol Cell Biology"], + "issn": "1759-4685", "alternate_issns": ["1673-520X"]}, "url": "https://www.semanticscholar.org/paper/906ec648aab69f9f823e672efcffd7f06ca3f361", + "title": "Exon-centric regulation of pyruvate kinase M alternative splicing + via mutually exclusive exons.", "abstract": "Alternative splicing of the pyruvate + kinase M gene (PK-M) can generate the M2 isoform and promote aerobic glycolysis + and tumor growth. However, the cancer-specific alternative splicing regulation + of PK-M is not completely understood. Here, we demonstrate that PK-M is regulated + by reciprocal effects on the mutually exclusive exons 9 and 10, such that + exon 9 is repressed and exon 10 is activated in cancer cells. Strikingly, + exonic, rather than intronic, cis-elements are key determinants of PK-M splicing + isoform ratios. Using a systematic sub-exonic duplication approach, we identify + a potent exonic splicing enhancer in exon 10, which differs from its homologous + counterpart in exon 9 by only two nucleotides. We identify SRSF3 as one of + the cognate factors, and show that this serine/arginine-rich protein activates + exon 10 and mediates changes in glucose metabolism. These findings provide + mechanistic insights into the complex regulation of alternative splicing of + a key regulator of the Warburg effect, and also have implications for other + genes with a similar pattern of alternative splicing.", "venue": "Journal + of Molecular Cell Biology", "year": 2012, "referenceCount": 28, "citationCount": + 85, "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3493165?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-04-01", "journal": {"volume": "4 2", "pages": "\n 79-87\n ", + "name": "Journal of molecular cell biology"}, "authors": [{"authorId": "47196879", + "name": "Zhenxun Wang"}, {"authorId": "145584048", "name": "D. Chatterjee"}, + {"authorId": "6967263", "name": "H. Y. Jeon"}, {"authorId": "38765885", "name": + "Martin Akerman"}, {"authorId": "3804233", "name": "M. V. Vander Heiden"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2742032", "name": + "A. Krainer"}]}, {"paperId": "a598fd46cac498bdf89799c2391c8b9b68bf89d1", "externalIds": + {"MAG": "2714245023", "CorpusId": 79885471}, "corpusId": 79885471, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/a598fd46cac498bdf89799c2391c8b9b68bf89d1", + "title": "Loss of the tumour suppressor inositol polyphosphate 4-phosphatase + type II in ovarian cancer-implications for therapy", "abstract": null, "venue": + "", "year": 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "5824068", + "name": "L. Ip"}, {"authorId": "1434829101", "name": "F. Cia-Viciano"}, {"authorId": + "80401680", "name": "Spanswick"}, {"authorId": "81917811", "name": "G. Pouigiannis"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1888139", "name": + "J. Hartley"}, {"authorId": "50728992", "name": "D. Hochhauser"}, {"authorId": + "7739224", "name": "C. Gewinner"}]}, {"paperId": "b28d47924bf6efab87ec65695afc5bf499e69ca3", + "externalIds": {"CorpusId": 207872577}, "corpusId": 207872577, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b28d47924bf6efab87ec65695afc5bf499e69ca3", + "title": "B . canadensis Campanian Hadrosaur Biomolecular Characterization + and Protein Sequences of the", "abstract": "clicking here. colleagues, clients, + or customers by , you can order high-quality copies for your If you wish to + distribute this article to others here. following the guidelines can be obtained + by Permission to republish or repurpose articles or portions of articles ): May + 15, 2012 www.sciencemag.org (this information is current as of The following + resources related to this article are available online at", "venue": "", "year": + 2012, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "5618773", + "name": "M. Schweitzer"}, {"authorId": "7494304", "name": "Wenxia Zheng"}, + {"authorId": "143615392", "name": "C. Organ"}, {"authorId": "2988211", "name": + "R. Avci"}, {"authorId": "8048771", "name": "Z. Suo"}, {"authorId": "4333053", + "name": "Lisa M. Freimark"}, {"authorId": "5457987", "name": "V. LeBleu"}, + {"authorId": "3418360", "name": "M. Duncan"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "40029126", "name": "J. Neveu"}, {"authorId": + "145588117", "name": "William Arbuthnot Sir Lane"}, {"authorId": "48894637", + "name": "J. Cottrell"}, {"authorId": "1701498", "name": "J. Horner"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5090009", "name": "R. Kalluri"}, + {"authorId": "3028470", "name": "J. Asara"}]}, {"paperId": "b39764fdceff4b8ed1a6efebc621d6c963f0f479", + "externalIds": {"PubMedCentral": "3537887", "MAG": "2172034799", "DOI": "10.1038/nsmb.2430", + "CorpusId": 9161210, "PubMed": "23178454"}, "corpusId": 9161210, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b39764fdceff4b8ed1a6efebc621d6c963f0f479", + "title": "Site\u2013Specific Monoubiquitination Activates Ras by Impeding + GTPase Activating Protein Function", "abstract": null, "venue": "Nature Structural + &Molecular Biology", "year": 2012, "referenceCount": 72, "citationCount": + 95, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3537887?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-10-10", "journal": {"volume": "20", "pages": "46 + - 52", "name": "Nature structural & molecular biology"}, "authors": [{"authorId": + "145564214", "name": "R. Baker"}, {"authorId": "7268742", "name": "Steven + M. Lewis"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "5527411", + "name": "Emily M. Wilkerson"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144226889", "name": + "B. Kuhlman"}, {"authorId": "1710306", "name": "H. Dohlman"}, {"authorId": + "46713144", "name": "S. Campbell"}]}, {"paperId": "b42affde6cdb6766aa690f5ae50e81e0f06fffbe", + "externalIds": {"MAG": "2318294786", "DOI": "10.1158/1538-7445.PANCA2012-A51", + "CorpusId": 88291245}, "corpusId": 88291245, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/b42affde6cdb6766aa690f5ae50e81e0f06fffbe", + "title": "Abstract A51: Oncogenic Kras is required for pancreatic tumor maintenance + through the regulation of anabolic glucose metabolism.", "abstract": "Tumor + maintenance relies on continued activity of driver oncogenes, although their + rate-limiting role is highly context-dependent. Oncogenic Kras mutation is + the signature event in pancreatic ductal adenocarcinoma (PDAC), serving a + critical role in tumor initiation. Here, an inducible KrasG12D-driven PDAC + mouse model establishes that advanced PDAC remain strictly dependent on KrasG12D + expression. Transcriptome and metabolomic analysis indicate that KrasG12D + serves a vital role in controlling tumor metabolism through stimulation of + glucose uptake and channeling of glucose intermediates into the hexosamine + biosynthesis and pentose phosphate pathways (PPP). These studies also reveal + that oncogenic Kras promotes ribose biogenesis. Unlike canonical models, we + demonstrate that KrasG12D drives glycolysis intermediates into the non-oxidative + PPP, thereby decoupling ribose biogenesis from NADP/NADPH-mediated redox control. + Together, this work provides in vivo mechanistic insights into how oncogenic + Kras promotes metabolic reprogramming in native tumors and illuminates potential + metabolic targets that can be exploited for therapeutic benefit in PDAC. Citation + Format: Costas Lyssiotis, Haoqiang Ying, Alec Kimmelman, Ronald DePinho, Lewis + Cantley. Oncogenic Kras is required for pancreatic tumor maintenance through + the regulation of anabolic glucose metabolism. [abstract]. In: Proceedings + of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; + Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 + Suppl):Abstract nr A51.", "venue": "", "year": 2012, "referenceCount": 0, + "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2012-07-15", "journal": {"volume": + "72", "name": "Cancer Research"}, "authors": [{"authorId": "4901222", "name": + "C. Lyssiotis"}, {"authorId": "33312849", "name": "H. Ying"}, {"authorId": + "4668673", "name": "A. Kimmelman"}, {"authorId": "5593407", "name": "R. DePinho"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ba2759db57fad26a4515e84b28006e9e519f3f96", + "externalIds": {"CorpusId": 251233195}, "corpusId": 251233195, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/ba2759db57fad26a4515e84b28006e9e519f3f96", + "title": "I (cid:1) B Kinase (cid:2) Phosphorylation of TRAF4 Downregulates + Innate Immune Signaling", "abstract": "Despite their homology, I (cid:1) B + kinase (cid:2) (IKK (cid:2) ) and IKK (cid:3) have divergent roles in NF- + (cid:1) B signaling. IKK (cid:3) strongly activates NF- (cid:1) B while IKK + (cid:2) can downregulate NF- (cid:1) B under certain circumstances. Given + this, identifying independent substrates for these kinases could help delineate + their divergent roles. Peptide substrate array technology followed by bioinformatic + screening identi\ufb01ed TRAF4 as a substrate for IKK (cid:2) . Like IKK (cid:2) + , TRAF4 is atypical within its family because it is the only TRAF family member + to negatively regulate innate immune signaling. IKK (cid:2) \u2019s phosphorylation + of serine-426 on TRAF4 was required for this negative regulation. Binding + to the Crohn\u2019s disease susceptibility protein, NOD2, is required for + TRAF4 phosphorylation and subsequent inhibition of NOD2 signaling. Structurally, + serine-426 resides within an exaggerated (cid:3) -bulge in TRAF4 that is not + present in the other TRAF proteins, and phosphorylation of this site provides + a structural basis for the atypical function of TRAF4 and its atypical role + in NOD2", "venue": "", "year": 2012, "referenceCount": 57, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "5203393", + "name": "Jill M. Marinis"}, {"authorId": "6742227", "name": "Jessica E. Hutti"}, + {"authorId": "6842553", "name": "C. Homer"}, {"authorId": "2047419", "name": + "B. Cobb"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145258453", + "name": "C. McDonald"}, {"authorId": "70453966", "name": "Derek Abbotta"}]}, + {"paperId": "bc32c53da1bfe292d251d3e61e10d0db947b8833", "externalIds": {"CorpusId": + 13910125}, "corpusId": 13910125, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/bc32c53da1bfe292d251d3e61e10d0db947b8833", + "title": "Somatic Mutations of PIK 3 R 1 Promote Gliomagenesis", "abstract": + "The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration + in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer + Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types, + but the tumorigenic activity of these mutations has not been demonstrated + in GBM. We show here that somatic mutations in the iSH2 domain of PIK3R1 act + as oncogenic driver events. Specifically, introduction of a subset of the + mutations identified in human GBM, in the nSH2 and iSH2 domains, increases + signaling through the PI3K pathway and promotes tumorigenesis of primary normal + human astrocytes in an orthotopic xenograft model. Furthermore, we show that + cells that are dependent on mutant P85a-mediated PI3K signaling exhibit increased + sensitivity to a small molecule inhibitor of AKT. Together, these results + suggest that GBM patients whose tumors carry mutant PIK3R1 alleles may benefit + from treatment with inhibitors of AKT. Citation: Quayle SN, Lee JY, Cheung + LWT, Ding L, Wiedemeyer R, et al. (2012) Somatic Mutations of PIK3R1 Promote + Gliomagenesis. PLoS ONE 7(11): e49466. doi:10.1371/journal.pone.0049466 Editor: + Maria G. Castro, University of Michigan School of Medicine, United States + of America Received July 20, 2012; Accepted October 9, 2012; Published November + 14, 2012 Copyright: 2012 Quayle et al. This is an open-access article distributed + under the terms of the Creative Commons Attribution License, which permits + unrestricted use, distribution, and reproduction in any medium, provided the + original author and source are credited. Funding: This work was supported + by a fellowship from the Canadian Institutes of Health (to SNQ), grants from + the Sontag Foundation and the Goldhirsh Foundation (to KLL), a grant from + the Ben and Catherine Ivy Foundation (to LC), and National Institutes of Health + grants U01CA141508, U24CA143845, and RC2CA148268 (to LC), PO1CA095616 (to + KLL and LC), and U01CA168394 (to GBM and LC). The funders had no role in study + design, data collection and analysis, decision to publish, or preparation + of the manuscript. Competing Interests: The authors have declared that no + competing interests exist. * E-mail: lchin@mdanderson.org \u00a4 Current address: + Department of Genomic Medicine and Institute for Applied Cancer Science, The + University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States + of America", "venue": "", "year": 2012, "referenceCount": 22, "citationCount": + 4, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "3696841", "name": "S. Quayle"}, + {"authorId": "46663676", "name": "Jennifer Y. Lee"}, {"authorId": "50005741", + "name": "L. W. Cheung"}, {"authorId": "49594724", "name": "L. Ding"}, {"authorId": + "5970725", "name": "R. Wiedemeyer"}, {"authorId": "31662497", "name": "Robert + W. Dewan"}, {"authorId": "1422124289", "name": "Emmet Huang-Hobbs"}, {"authorId": + "117378315", "name": "L. Zhuang"}, {"authorId": "2111010098", "name": "R. + Wilson"}, {"authorId": "5627829", "name": "K. Ligon"}, {"authorId": "2241330", + "name": "G. Mills"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144750835", "name": "L. Chin"}]}, {"paperId": "c1a923c787ca22f145e4c4db78373185a4416eb3", + "externalIds": {"MAG": "2067636697", "DOI": "10.1126/science.1223140", "CorpusId": + 206541851, "PubMed": "22605741"}, "corpusId": 206541851, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/c1a923c787ca22f145e4c4db78373185a4416eb3", + "title": "Ancient Sensor for Ancient Drug", "abstract": "A common drug has + an unexpected effect on a metabolic enzyme that stimulates fat utilization. + Salicylate, a compound found in willow tree bark, is the active breakdown + product of aspirin, and has been used for medicinal purposes since ancient + times. However, the molecular mechanism underlying the beneficial effects + of salicylate has been unclear. On page 918 of this issue, Hawley et al. (1) + show that salicylate activates the cellular metabolic regulator adenosine + monophosphate (AMP)\u2013activated protein kinase (AMPK), which stimulates + fat utilization in mice.", "venue": "Science", "year": 2012, "referenceCount": + 14, "citationCount": 18, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["LettersAndComments", "JournalArticle"], "publicationDate": "2012-05-18", + "journal": {"volume": "336", "pages": "813 - 814", "name": "Science"}, "authors": + [{"authorId": "4426388", "name": "R. Shaw"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "cc5b3b6095ae6e0a3d8a1c7791afef5d6598cc66", "externalIds": + {"DOI": "10.1038/ncb2629", "CorpusId": 54467103, "PubMed": "23178880"}, "corpusId": + 54467103, "publicationVenue": {"id": "7d182b83-7d8d-43fb-9fd6-ae67fbafab20", + "name": "Nature Cell Biology", "type": "journal", "alternate_names": ["Nat + Cell Biology"], "issn": "1465-7392", "url": "http://www.nature.com/naturecellbiology", + "alternate_urls": ["https://www.nature.com/ncb/"]}, "url": "https://www.semanticscholar.org/paper/cc5b3b6095ae6e0a3d8a1c7791afef5d6598cc66", + "title": "ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 + promotes the Warburg effect.", "abstract": null, "venue": "Nature Cell Biology", + "year": 2012, "referenceCount": 0, "citationCount": 292, "influentialCitationCount": + 19, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3511602?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": null, "journal": + {"volume": "14 12", "pages": "\n 1295-304\n ", "name": "Nature + cell biology"}, "authors": [{"authorId": "143956168", "name": "Weiwei Yang"}, + {"authorId": "3169180", "name": "Yanhua Zheng"}, {"authorId": "143733371", + "name": "Yan Xia"}, {"authorId": "2579875", "name": "Haitao Ji"}, {"authorId": + "48283607", "name": "Xiaomin Chen"}, {"authorId": "152831013", "name": "F. + Guo"}, {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "50138848", + "name": "K. Aldape"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5467266", "name": "Zhimin Lu"}]}, {"paperId": "cd8c573f52f641dd51ebb850be093667ef3b64a7", + "externalIds": {"MAG": "2208451982", "DOI": "10.1007/978-1-4614-0598-6_13", + "CorpusId": 86035311}, "corpusId": 86035311, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/cd8c573f52f641dd51ebb850be093667ef3b64a7", + "title": "Cancer Cell Metabolism", "abstract": null, "venue": "", "year": + 2012, "referenceCount": 80, "citationCount": 246, "influentialCitationCount": + 8, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": {"volume": "", "pages": "245-261", "name": ""}, "authors": + [{"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": "2268976", "name": + "J. Locasale"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d40354854dd5c47f83de55b9b3f6aff7b0c27700", "externalIds": {"PubMedCentral": + "3408500", "MAG": "2147592527", "DOI": "10.1371/journal.pone.0041494", "CorpusId": + 5973641, "PubMed": "22859992"}, "corpusId": 5973641, "publicationVenue": {"id": + "0aed7a40-85f3-4c66-9e1b-c1556c57001b", "name": "PLoS ONE", "type": "journal", + "alternate_names": ["Plo ONE", "PLOS ONE", "PLO ONE"], "issn": "1932-6203", + "url": "https://journals.plos.org/plosone/", "alternate_urls": ["http://www.plosone.org/"]}, + "url": "https://www.semanticscholar.org/paper/d40354854dd5c47f83de55b9b3f6aff7b0c27700", + "title": "Development of a High-Throughput Assay for Identifying Inhibitors + of TBK1 and IKK\u03b5", "abstract": "IKK\u03b5 and TBK1 are noncanonical IKK + family members which regulate inflammatory signaling pathways and also play + important roles in oncogenesis. However, few inhibitors of these kinases have + been identified. While the substrate specificity of IKK\u03b5 has recently + been described, the substrate specificity of TBK1 is unknown, hindering the + development of high-throughput screening technologies for inhibitor identification. + Here, we describe the optimal substrate phosphorylation motif for TBK1, and + show that it is identical to the phosphorylation motif previously described + for IKK\u03b5. This information enabled the design of an optimal TBK1/IKK\u03b5 + substrate peptide amenable to high-throughput screening and we assayed a 6,006 + compound library that included 4,727 kinase-focused compounds to discover + in vitro inhibitors of TBK1 and IKK\u03b5. 227 compounds in this library inhibited + TBK1 at a concentration of 10 \u00b5M, while 57 compounds inhibited IKK\u03b5. + Together, these data describe a new high-throughput screening assay which + will facilitate the discovery of small molecule TBK1/IKK\u03b5 inhibitors + possessing therapeutic potential for both inflammatory diseases and cancer.", + "venue": "PLoS ONE", "year": 2012, "referenceCount": 41, "citationCount": + 32, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0041494&type=printable", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2012-07-30", "journal": {"volume": + "7", "name": "PLoS ONE"}, "authors": [{"authorId": "6742227", "name": "Jessica + E. Hutti"}, {"authorId": "22153825", "name": "M. Porter"}, {"authorId": "4108773", + "name": "Adam W. Cheely"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2108428054", "name": "Xiaodong Wang"}, {"authorId": "32133533", + "name": "D. Kireev"}, {"authorId": "2157007", "name": "A. Baldwin"}, {"authorId": + "5202479", "name": "W. Janzen"}]}, {"paperId": "d4df8adf1c918774f11f8268cbb182e00f5e901d", + "externalIds": {"MAG": "2146708267", "DOI": "10.1016/j.nut.2012.07.004", "CorpusId": + 5565559, "PubMed": "22925542"}, "corpusId": 5565559, "publicationVenue": {"id": + "efda22ae-07c9-475b-8193-699753a01eb0", "name": "Nutrition (Burbank, Los Angeles + County, Calif.)", "type": "journal", "alternate_names": ["Nutrition", "Nutr + (burbank los angel Cty Calif"], "issn": "0899-9007", "url": "https://www.journals.elsevier.com/nutrition", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/08999007", + "http://www.nutritionjrnl.com/"]}, "url": "https://www.semanticscholar.org/paper/d4df8adf1c918774f11f8268cbb182e00f5e901d", + "title": "Sugar free, cancer free?", "abstract": null, "venue": "Nutrition + (Burbank, Los Angeles County, Calif.)", "year": 2012, "referenceCount": 6, + "citationCount": 6, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3746332?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["LettersAndComments", "Editorial"], "publicationDate": + "2012-10-01", "journal": {"volume": "28 10", "pages": "\n 1036\n ", + "name": "Nutrition"}, "authors": [{"authorId": "6324437", "name": "A. Myers"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "dd72a5e83d3cc7e607c99c3cb5062da509b81ae2", + "externalIds": {"MAG": "2332477414", "DOI": "10.1158/1940-6207.PREV-12-OP-03", + "CorpusId": 87715942}, "corpusId": 87715942, "publicationVenue": {"id": "30248bd8-0140-4a2a-b2f7-d817cf173fdd", + "name": "Cancer Prevention Research", "type": "journal", "alternate_names": + ["Cancer Prev Res"], "issn": "1940-6215", "url": "https://cancerpreventionresearch.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/dd72a5e83d3cc7e607c99c3cb5062da509b81ae2", + "title": "Abstract OP-03: PI 3-Kinase, AMPK, and Cancer", "abstract": "Phosphoinositide + 3-kinase (PI3K) is a central enzyme in a signaling pathway that mediates cellular + responses to growth factors. This enzyme phosphorylates the 3 position of + phosphatidylinositol-4,5-bisphosphate to produce phosphatidylinositol-3,4,5-trisphosphate + (PIP3) at the plasma membrane. A number of signaling proteins, including the + Ser/Thr protein kinases, AKT and PDK1, contain pleckstrin homology domains + that bind specifically to PIP3. Thus, the generation of PIP3 at the plasma + membrane in response to activation of PI3K by insulin and by growth factors + results in the initiation of downstream Ser/Thr phosphorylation cascades that + control a variety of cellular responses. The signaling pathway downstream + of PI3K is highly conserved from worms and flies to humans and genetic analysis + of the pathway has revealed a conserved role in regulating glucose metabolism + and cell growth. Based on deletion of genes encoding the catalytic or regulatory + subunits of PI3K in the mouse, PI3K mediates insulin dependent regulation + of glucose metabolism, and defects in activation of this pathway result in + insulin resistance. Studies over the past decade have revealed considerable + cross-talk between the PI3K signaling pathway and AMP activated protein kinase + (AMPK). These enzymes have opposing effects in regard to activating mTOR signaling, + but have complimentary effects in stimulating glucose uptake. These two enzymes + also play complex roles in cancers. Activating mutations in PIK3CA, encoding + the p110alpha catalytic subunit of PI3K or inactivating mutations in PTEN, + a phosphoinositide 3-phosphatases that reverses the effects of PI3K, are among + the most common events in solid tumors. Loss of function mutations in LKB1, + a protein kinase that phosphorylates and activates AMPK, can also drive cancers. + We have generated mouse models in which a mutated form of the PIK3CA gene + is expressed in a tissue specific and reversibly inducible manner. These mice + develop cancers that are dependent on continuous expression of the mutant + PIK3CA gene. The PIK3CA driven tumors are FDG-PET positive and turning off + PI 3-Kinase with PI3K inhibitors that are in human clinical trials results + in an acute decline in FDG-PET signal that precedes tumor shrinkage. These + results suggest that the ability of PI3K to stimulate high rates of glucose + uptake and metabolism may be critical for the survival of PIK3CA mutant tumors. + In contrast, drugs that activate AMPK may be useful in preventing cancers. + Activation of AMPK in tumor cells using drugs, such as metformin or phenformin + can suppress tumor cell growth in a cell-autonomous manner. In addition, metformin + and phenformin, through actions in the liver, can lower serum glucose and + insulin levels and thereby indirectly suppress tumor cell growth that is dependent + on insulin and glucose. The role of PI3K inhibitors and AMPK activators for + preventing or treating cancers in mouse models and in human trials will be + discussed. Citation Format: Lewis C. Cantley. PI 3-Kinase, AMPK, and Cancer. + [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference + on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia + (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr OP-03.", "venue": + "Cancer Prevention Research", "year": 2012, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2012-11-01", "journal": {"volume": + "5", "pages": "OP-03 - OP-03", "name": "Cancer Prevention Research"}, "authors": + [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "e0d8fbf2841972cf2f605591226e7d3004c6b185", + "externalIds": {"MAG": "2163993295", "DOI": "10.1128/MCB.00106-12", "CorpusId": + 36778340, "PubMed": "22547678"}, "corpusId": 36778340, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/e0d8fbf2841972cf2f605591226e7d3004c6b185", + "title": "I\u03baB Kinase \u03b1 Phosphorylation of TRAF4 Downregulates Innate + Immune Signaling", "abstract": "ABSTRACT Despite their homology, I\u03baB + kinase \u03b1 (IKK\u03b1) and IKK\u03b2 have divergent roles in NF-\u03baB + signaling. IKK\u03b2 strongly activates NF-\u03baB while IKK\u03b1 can downregulate + NF-\u03baB under certain circumstances. Given this, identifying independent + substrates for these kinases could help delineate their divergent roles. Peptide + substrate array technology followed by bioinformatic screening identified + TRAF4 as a substrate for IKK\u03b1. Like IKK\u03b1, TRAF4 is atypical within + its family because it is the only TRAF family member to negatively regulate + innate immune signaling. IKK\u03b1''s phosphorylation of serine-426 on TRAF4 + was required for this negative regulation. Binding to the Crohn''s disease + susceptibility protein, NOD2, is required for TRAF4 phosphorylation and subsequent + inhibition of NOD2 signaling. Structurally, serine-426 resides within an exaggerated + \u03b2-bulge in TRAF4 that is not present in the other TRAF proteins, and + phosphorylation of this site provides a structural basis for the atypical + function of TRAF4 and its atypical role in NOD2 signaling.", "venue": "Molecular + and Cellular Biology", "year": 2012, "referenceCount": 56, "citationCount": + 23, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3434482?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-04-30", "journal": {"volume": "32", "pages": "2479 + - 2489", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "5203393", "name": "Jill M. Marinis"}, {"authorId": "6742227", "name": "Jessica + E. Hutti"}, {"authorId": "6842553", "name": "C. Homer"}, {"authorId": "2047419", + "name": "B. Cobb"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "145258453", "name": "C. McDonald"}, {"authorId": "145759174", "name": "Derek + W. Abbott"}]}, {"paperId": "e22e66712a29b2bdc46028e18b838655af862f14", "externalIds": + {"MAG": "2915325753", "DOI": "10.1158/1078-0432.CCR-12-2891", "CorpusId": + 42522937, "PubMed": "22977188"}, "corpusId": 42522937, "publicationVenue": + {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", "name": "Clinical Cancer Research", + "type": "journal", "alternate_names": ["Clin Cancer Res"], "issn": "1078-0432", + "url": "https://clincancerres.aacrjournals.org/", "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/e22e66712a29b2bdc46028e18b838655af862f14", + "title": "AACR Cancer Progress Report 2012", "abstract": null, "venue": "Clinical + Cancer Research", "year": 2012, "referenceCount": 132, "citationCount": 33, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://clincancerres.aacrjournals.org/content/clincanres/18/21_Supplement/S1.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2012-11-01", "journal": + {"volume": "18", "pages": "S1 - S100", "name": "Clinical Cancer Research"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6230610", + "name": "W. Dalton"}, {"authorId": "4135978", "name": "R. DuBois"}, {"authorId": + "3897572", "name": "O. Finn"}, {"authorId": "153020660", "name": "P. A. Futreal"}, + {"authorId": "2900051", "name": "T. Golub"}, {"authorId": "5559905", "name": + "W. Hait"}, {"authorId": "144996908", "name": "G. Lozano"}, {"authorId": "2427647", + "name": "J. Maris"}, {"authorId": "81233537", "name": "W. Nelson"}, {"authorId": + "4165356", "name": "C. Sawyers"}, {"authorId": "2610390", "name": "S. Schreiber"}, + {"authorId": "3059932", "name": "M. Spitz"}, {"authorId": "6985830", "name": + "P. Steeg"}]}, {"paperId": "ebf8d017db53889407884bd21e4d8bf6ae1b8f44", "externalIds": + {"MAG": "2106284801", "DOI": "10.1074/mcp.M111.014688", "CorpusId": 8570874, + "PubMed": "22240505"}, "corpusId": 8570874, "publicationVenue": {"id": "f13c562f-8530-4cef-a857-00c4f2d8403d", + "name": "Molecular & Cellular Proteomics", "type": "journal", "alternate_names": + ["Mol Cell Proteom"], "issn": "1535-9476", "url": "https://www.mcponline.org/", + "alternate_urls": ["http://www.mcponline.org/"]}, "url": "https://www.semanticscholar.org/paper/ebf8d017db53889407884bd21e4d8bf6ae1b8f44", + "title": "Metabolomics of Human Cerebrospinal Fluid Identifies Signatures + of Malignant Glioma*", "abstract": "Cerebrospinal fluid is routinely collected + for the diagnosis and monitoring of patients with neurological malignancies. + However, little is known as to how its constituents may change in a patient + when presented with a malignant glioma. Here, we used a targeted mass-spectrometry + based metabolomics platform using selected reaction monitoring with positive/negative + switching and profiled the relative levels of over 124 polar metabolites present + in patient cerebrospinal fluid. We analyzed the metabolic profiles from 10 + patients presenting malignant gliomas and seven control patients that did + not present malignancy to test whether a small sample size could provide statistically + significant signatures. We carried out multiple unbiased forms of classification + using a series of unsupervised techniques and identified metabolic signatures + that distinguish malignant glioma patients from the control patients. One + subtype identified contained metabolites enriched in citric acid cycle components. + Newly diagnosed patients segregated into a different subtype and exhibited + low levels of metabolites involved in tryptophan metabolism, which may indicate + the absence of an inflammatory signature. Together our results provide the + first global assessment of the polar metabolic composition in cerebrospinal + fluid that accompanies malignancy, and demonstrate that data obtained from + high throughput mass spectrometry technology may have suitable predictive + capabilities for the identification of biomarkers and classification of neurological + diseases.", "venue": "Molecular & Cellular Proteomics", "year": 2012, "referenceCount": + 66, "citationCount": 85, "influentialCitationCount": 3, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Medicine", "source": "s2-fos-model"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-01-12", "journal": {"volume": "11", "name": "Molecular + & Cellular Proteomics"}, "authors": [{"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "1853856", "name": "T. Melman"}, {"authorId": "2110553093", "name": + "Susan Song"}, {"authorId": "48520140", "name": "Xuemei Yang"}, {"authorId": + "6784962", "name": "K. Swanson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1913037", "name": "E. Wong"}, {"authorId": "3028470", "name": + "J. Asara"}]}, {"paperId": "fa34bfa3a8a239bbc12dd368166215778eaeb733", "externalIds": + {"MAG": "2038202279", "DOI": "10.1038/onc.2011.262", "CorpusId": 29325865, + "PubMed": "21725358"}, "corpusId": 29325865, "publicationVenue": {"id": "55bed249-d30f-456b-9d2c-a51dc149cb7a", + "name": "Oncogene", "type": "journal", "issn": "0950-9232", "url": "http://www.nature.com/onc/", + "alternate_urls": ["http://www.nature.com/onc", "http://www.naturesj.com/onc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/fa34bfa3a8a239bbc12dd368166215778eaeb733", + "title": "The SRC-associated protein CUB Domain-Containing Protein-1 regulates + adhesion and motility", "abstract": null, "venue": "Oncogene", "year": 2012, + "referenceCount": 54, "citationCount": 36, "influentialCitationCount": 1, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3777806?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2012-02-02", "journal": {"volume": + "31", "pages": "653-663", "name": "Oncogene"}, "authors": [{"authorId": "1714039", + "name": "C. Benes"}, {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4324390", "name": "S. Soltoff"}]}, + {"paperId": "fabaac3360085ef8aa1880b3085b4ee49a6799b7", "externalIds": {"MAG": + "2119489521", "DOI": "10.1161/CIRCULATIONAHA.112.115592", "CorpusId": 25448659, + "PubMed": "23019294"}, "corpusId": 25448659, "publicationVenue": {"id": "0d67273f-71c8-43f4-a642-9c384870ccb2", + "name": "Circulation", "type": "journal", "issn": "0009-7322", "url": "http://gateway.ovid.com/ovidweb.cgi?AN=00002060-000000000-00000&D=ovft&MODE=ovid&NEWS=N&PAGE=toc&T=JS", + "alternate_urls": ["http://circ.ahajournals.org/"]}, "url": "https://www.semanticscholar.org/paper/fabaac3360085ef8aa1880b3085b4ee49a6799b7", + "title": "Pathological Role of Serum- and Glucocorticoid-Regulated Kinase + 1 in Adverse Ventricular Remodeling", "abstract": "Background\u2014 Heart + failure is a growing cause of morbidity and mortality. Cardiac phosphatidylinositol + 3-kinase signaling promotes cardiomyocyte survival and function, but it is + paradoxically activated in heart failure, suggesting that chronic activation + of this pathway may become maladaptive. Here, we investigated the downstream + phosphatidylinositol 3-kinase effector, serum- and glucocorticoid-regulated + kinase-1 (SGK1), in heart failure and its complications. Methods and Results\u2014 + We found that cardiac SGK1 is activated in human and murine heart failure. + We investigated the role of SGK1 in the heart by using cardiac-specific expression + of constitutively active or dominant-negative SGK1. Cardiac-specific activation + of SGK1 in mice increased mortality, cardiac dysfunction, and ventricular + arrhythmias. The proarrhythmic effects of SGK1 were linked to biochemical + and functional changes in the cardiac sodium channel and could be reversed + by treatment with ranolazine, a blocker of the late sodium current. Conversely, + cardiac-specific inhibition of SGK1 protected mice after hemodynamic stress + from fibrosis, heart failure, and sodium channel alterations. Conclusions\u2014 + SGK1 appears both necessary and sufficient for key features of adverse ventricular + remodeling and may provide a novel therapeutic target in cardiac disease.", + "venue": "Circulation", "year": 2012, "referenceCount": 50, "citationCount": + 90, "influentialCitationCount": 7, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.112.115592", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2012-10-30", "journal": {"volume": "126", "pages": "2208\u20132219", + "name": "Circulation"}, "authors": [{"authorId": "2116117659", "name": "Saumya + Das"}, {"authorId": "6342525", "name": "T. Aiba"}, {"authorId": "38355094", + "name": "M. Rosenberg"}, {"authorId": "10718959", "name": "K. Hessler"}, {"authorId": + "47343594", "name": "C. Xiao"}, {"authorId": "1781556", "name": "P. Quintero"}, + {"authorId": "6513631", "name": "Filomena Ottaviano"}, {"authorId": "47830085", + "name": "Ashley C. Knight"}, {"authorId": "40193551", "name": "E. Graham"}, + {"authorId": "47428213", "name": "P. Bostr\u00f6m"}, {"authorId": "40419316", + "name": "M. Morissette"}, {"authorId": "6020889", "name": "F. del Monte"}, + {"authorId": "69874482", "name": "M. Begley"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4504266", "name": "P. Ellinor"}, {"authorId": + "2338824", "name": "G. Tomaselli"}, {"authorId": "144061154", "name": "A. + Rosenzweig"}]}, {"paperId": "04bb3743d466fe1cf9bb82d9efcb35802603ff0a", "externalIds": + {"MAG": "2087974103", "DOI": "10.1126/science.1201678", "CorpusId": 28294963, + "PubMed": "21436401"}, "corpusId": 28294963, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/04bb3743d466fe1cf9bb82d9efcb35802603ff0a", + "title": "AMP-Activated Protein Kinase Regulates Neuronal Polarization by + Interfering with PI 3-Kinase Localization", "abstract": "A bioenergy-sensing + pathway determines axon initiation and growth in neurons. Axon-dendrite polarization + is crucial for neural network wiring and information processing in the brain. + Polarization begins with the transformation of a single neurite into an axon + and its subsequent rapid extension, which requires coordination of cellular + energy status to allow for transport of building materials to support axon + growth. We found that activation of the energy-sensing adenosine 5\u2032-monophosphate + (AMP)\u2013activated protein kinase (AMPK) pathway suppressed axon initiation + and neuronal polarization. Phosphorylation of the kinesin light chain of the + Kif5 motor protein by AMPK disrupted the association of the motor with phosphatidylinositol + 3-kinase (PI3K), preventing PI3K targeting to the axonal tip and inhibiting + polarization and axon growth.", "venue": "Science", "year": 2011, "referenceCount": + 32, "citationCount": 75, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3325765?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-04-08", "journal": {"volume": + "332", "pages": "247 - 251", "name": "Science"}, "authors": [{"authorId": + "144098874", "name": "S. Amato"}, {"authorId": "120280954", "name": "Xiuxin + Liu"}, {"authorId": "29089092", "name": "B. Zheng"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "144100263", "name": "P. Rakic"}, {"authorId": + "80648567", "name": "H. Man"}]}, {"paperId": "07cf76182e2c4109cb7d912a699c7731f600b0e6", + "externalIds": {"MAG": "2067314418", "DOI": "10.1021/pr200578n", "CorpusId": + 41114447, "PubMed": "21774532"}, "corpusId": 41114447, "publicationVenue": + {"id": "c7bbca07-9604-48a6-85d8-512fa663722e", "name": "Journal of Proteome + Research", "type": "journal", "alternate_names": ["J Proteome Res"], "issn": + "1535-3893", "url": "https://pubs.acs.org/journal/jprobs", "alternate_urls": + ["http://pubs.acs.org/journals/jprobs/", "http://pubs.acs.org/journals/jprobs/index.html", + "http://pubs.acs.org/journal/jprobs"]}, "url": "https://www.semanticscholar.org/paper/07cf76182e2c4109cb7d912a699c7731f600b0e6", + "title": "Proteomic screening method for phosphopeptide motif binding proteins + using peptide libraries.", "abstract": "Phosphopeptide binding domains mediate + the directed and localized assembly of protein complexes essential to intracellular + kinase signaling. To identify phosphopeptide binding proteins, we developed + a proteomic screening method using immobilized partially degenerate phosphopeptide + mixtures combined with SILAC and microcapillary LC-MS/MS. The method was used + to identify proteins that specifically bound to phosphorylated peptide library + affinity matrices, including pTyr, and the motifs pSer/pThr-Pro, pSer/pThr-X-X-X-pSer/pThr, + pSer/pThr-Glu/Asp, or pSer/pThr-pSer/pThr in degenerate sequence contexts. + Heavy and light SILAC lysates were applied to columns containing these phosphorylated + and nonphosphorylated (control) peptide libraries respectively, and bound + proteins were eluted, combined, digested, and analyzed by LC-MS/MS using a + hybrid quadrupole-TOF mass spectrometer. Heavy/light peptide ion ratios were + calculated, and peptides that yielded ratios greater than \u223c3:1 were considered + as being from potential phosphopeptide binding proteins since this ratio represents + the lowest ratio from a known positive control. Many of those identified were + known phosphopeptide-binding proteins, including the SH2 domain containing + p85 subunit of PI3K bound to pTyr, 14-3-3 bound to pSer/pThr-Asp/Glu, polo-box + domain containing PLK1 and Pin1 bound to pSer/pThr-Pro, and pyruvate kinase + M2 binding to pTyr. Approximately half of the hits identified by the peptide + library screens were novel. Protein domain enrichment analysis revealed that + most pTyr hits contain SH2 domains, as expected, and to a lesser extent SH3, + C1, STAT, Tyr phosphatase, Pkinase, C2, and PH domains; however, pSer/pThr + motifs did not reveal enriched domains across hits.", "venue": "Journal of + Proteome Research", "year": 2011, "referenceCount": 37, "citationCount": 16, + "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc3174226?pdf=render", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2011-09-02", "journal": {"volume": "10 9", "pages": "\n 4158-64\n ", + "name": "Journal of proteome research"}, "authors": [{"authorId": "4164415", + "name": "H. Christofk"}, {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3028470", "name": "J. Asara"}]}, + {"paperId": "0a9f908f710d40676d7dfc1a5389b32e667f2669", "externalIds": {"MAG": + "3019994392", "DOI": "10.3410/f.13411026.14782149", "CorpusId": 223780016}, + "corpusId": 223780016, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/0a9f908f710d40676d7dfc1a5389b32e667f2669", + "title": "Faculty Opinions recommendation of Genetic and functional studies + implicate HIF1\u03b1 as a 14q kidney cancer suppressor gene.", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-12-19", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "1ce5b5efac31327266d7872bf110b7a02d35068e", "externalIds": {"CorpusId": + 207767691}, "corpusId": 207767691, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/1ce5b5efac31327266d7872bf110b7a02d35068e", + "title": "Yonghao Yu Substrate That Negatively Regulates Insulin Signaling + Phosphoproteomic Analysis Identifies Grb 10 as an mTORC 1", "abstract": "clicking + here. colleagues, clients, or customers by , you can order high-quality copies + for your If you wish to distribute this article to others here. following + the guidelines can be obtained by Permission to republish or repurpose articles + or portions of articles ): June 12, 2011 www.sciencemag.org (this infomation + is current as of The following resources related to this article are available + online at", "venue": "", "year": 2011, "referenceCount": 0, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Business", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "40508577", "name": "Yonghao Yu"}, + {"authorId": "6168327", "name": "Sang-Oh Yoon"}, {"authorId": "4612853", "name": + "G. Poulogiannis"}, {"authorId": "144785850", "name": "Qian Yang"}, {"authorId": + "50088305", "name": "X. Ma"}, {"authorId": "1705488", "name": "J. Vill\u00e9n"}, + {"authorId": "8429203", "name": "Neil Kubica"}, {"authorId": "34846304", "name": + "G. Hoffman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2665934", "name": "S. Gygi"}]}, {"paperId": "2318a667d943d83bd38192d5f611f91209beaa74", + "externalIds": {"MAG": "2123316972", "DOI": "10.1158/2159-8274.CD-10-0022", + "CorpusId": 26399965, "PubMed": "22140652"}, "corpusId": 26399965, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/2318a667d943d83bd38192d5f611f91209beaa74", + "title": "Characterization of KRAS rearrangements in metastatic prostate cancer.", + "abstract": "UNLABELLED\nUsing an integrative genomics approach called amplification + breakpoint ranking and assembly analysis, we nominated KRAS as a gene fusion + with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line, originally + derived from prostate cancer metastasis to the brain. Interestingly, analysis + of tissues revealed that 2 of 62 metastatic prostate cancers harbored aberrations + at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces a fusion protein, + a specific knockdown of which attenuates cell invasion and xenograft growth. + Ectopic expression of the UBE2L3-KRAS fusion protein exhibits transforming + activity in NIH 3T3 fibroblasts and RWPE prostate epithelial cells in vitro + and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates MEK/ERK signaling, commonly + engaged by oncogenic mutant KRAS, and instead signals via AKT and p38 mitogen-activated + protein kinase (MAPK) pathways. This is the first report of a gene fusion + involving the Ras family, suggesting that this aberration may drive metastatic + progression in a rare subset of prostate cancers.\n\n\nSIGNIFICANCE\nThis + is the first description of an oncogenic gene fusion of KRAS, one of the most + studied proto-oncogenes. KRAS rearrangement may represent the driving mutation + in a rare subset of metastatic prostate cancers, emphasizing the importance + of RAS-RAF-MAPK signaling in this disease.", "venue": "Cancer Discovery", + "year": 2011, "referenceCount": 26, "citationCount": 102, "influentialCitationCount": + 3, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3227139?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-06-01", "journal": {"volume": "1 1", "pages": "\n 35-43\n ", + "name": "Cancer discovery"}, "authors": [{"authorId": "48631932", "name": + "Xiao-Song Wang"}, {"authorId": "39560950", "name": "Sunita Shankar"}, {"authorId": + "3113892", "name": "S. Dhanasekaran"}, {"authorId": "3913657", "name": "Bushra + Ateeq"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "49737962", + "name": "X. Jing"}, {"authorId": "48706636", "name": "Daniel H. Robinson"}, + {"authorId": "144457382", "name": "Q. Cao"}, {"authorId": "5608756", "name": + "John R. Prensner"}, {"authorId": "4221039", "name": "A. Yocum"}, {"authorId": + "2037452760", "name": "Rui Wang"}, {"authorId": "145571865", "name": "Daniel + F. Fries"}, {"authorId": "144202024", "name": "B. Han"}, {"authorId": "6382794", + "name": "I. Asangani"}, {"authorId": "152167434", "name": "Xuhong Cao"}, {"authorId": + "2154403330", "name": "Yong Li"}, {"authorId": "2716422", "name": "G. Omenn"}, + {"authorId": "5715823", "name": "D. Pflueger"}, {"authorId": "4059774", "name": + "A. Gopalan"}, {"authorId": "30582790", "name": "V. Reuter"}, {"authorId": + "4049626", "name": "E. Kahoud"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "144014266", "name": "M. Rubin"}, {"authorId": "145158003", "name": + "N. Palanisamy"}, {"authorId": "6088770", "name": "S. Varambally"}, {"authorId": + "2186786", "name": "A. Chinnaiyan"}]}, {"paperId": "246c0c64a06578efbcf0b93ea31d4608139aa728", + "externalIds": {"CorpusId": 10781664}, "corpusId": 10781664, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/246c0c64a06578efbcf0b93ea31d4608139aa728", + "title": "Integrated Systems and Technologies Using Tandem Mass Spectrometry + in Targeted Mode to Identify Activators of Class IA PI 3 K in Cancer", "abstract": + "Phosphatiditylinositide-3-kinase (PI3K) is activated in some cancers by direct + mutation, but it is activated more commonly in cancer by mutation of upstream + acting receptor tyrosine kinases (TK). At present, there is no systematic + method to determine which TK signaling cascades activate PI3K in certain cancers, + despite the likely utility of such information to help guide selectionof tyrosine + kinase inhibitor (TKI) drug strategies for personalized therapy. Here, we + present a quantitative liquid chromatography tandem mass spectrometry approach + that identifies upstream activators of PI3K both in vitro and in vivo. Using + non\u2013small cell lung carcinoma to illustrate this approach, we show a + correct identification of the mechanism of PI3K activation in several models, + thereby identifying the most appropriate TKI to downregulate PI3K signaling. + This approach also determined the molecular mechanisms and adaptors required + for PI3K activation following inhibition of the mTOR kinase TORC1. We further + validated the approach in breast cancer cells with mutational activation of + PIK3CA, where tandem mass spectrometry detected and quantitatively measured + the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K + activation. Overall, our findings establish amass spectrometric approach to + identify functional interactions that govern PI3K regulation in cancer cells. + Using this technique to define the pathways that activate PI3K signaling in + a given tumor could help inform clinical decision making by helping guide + personalized therapeutic strategies for different patients. Cancer Res; 71(18); + 5965\u201375. 2011 AACR.", "venue": "", "year": 2011, "referenceCount": 51, + "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + null, "authors": [{"authorId": "48520140", "name": "Xuemei Yang"}, {"authorId": + "4039016", "name": "Alexa B. Turke"}, {"authorId": "46315599", "name": "J. + Qi"}, {"authorId": "4846062", "name": "Youngchul Song"}, {"authorId": "5162072", + "name": "B. Rexer"}, {"authorId": "34988079", "name": "T. Miller"}, {"authorId": + "81090960", "name": "J. PasiA."}, {"authorId": "2067373625", "name": "Anne"}, + {"authorId": "2057460", "name": "C. Arteaga"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": + "3028470", "name": "J. Asara"}]}, {"paperId": "25c52aa0b060b367f88974e987d36e91a0838d78", + "externalIds": {"MAG": "2281345652", "DOI": "10.1016/j.cell.2011.06.050", + "CorpusId": 13893849, "PubMed": "21854985"}, "corpusId": 13893849, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/25c52aa0b060b367f88974e987d36e91a0838d78", + "title": "Metabolic Regulation of Protein N-Alpha-Acetylation by Bcl-xL Promotes + Cell Survival", "abstract": null, "venue": "Cell", "year": 2011, "referenceCount": + 48, "citationCount": 196, "influentialCitationCount": 12, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867411007665/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Computer Science", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2011-08-01", "journal": {"volume": "146", "pages": "607-620", "name": "Cell"}, + "authors": [{"authorId": "2906327", "name": "C. Yi"}, {"authorId": "4811754", + "name": "Heling Pan"}, {"authorId": "49911202", "name": "J. Seebacher"}, {"authorId": + "4629932", "name": "I. Jang"}, {"authorId": "1891857", "name": "S. Hyberts"}, + {"authorId": "6886706", "name": "G. Heffron"}, {"authorId": "35413264", "name": + "M. V. Heiden"}, {"authorId": "8092839", "name": "Renliang Yang"}, {"authorId": + "49515730", "name": "Fupeng Li"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "4536882", "name": "H. Sharfi"}, {"authorId": "1859720", "name": + "B. Zhai"}, {"authorId": "1398695904", "name": "R. Rodr\u00edguez-Mias"}, + {"authorId": "5619108", "name": "H. Luithardt"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2028224", "name": "G. Daley"}, {"authorId": "3028470", + "name": "J. Asara"}, {"authorId": "2665934", "name": "S. Gygi"}, {"authorId": + "145241228", "name": "G. Wagner"}, {"authorId": "11157072", "name": "Chuan-fa + Liu"}, {"authorId": "40146895", "name": "Junying Yuan"}]}, {"paperId": "3141ba16b8c5e721203a093cb2ea31360f584fb5", + "externalIds": {"MAG": "2167264978", "DOI": "10.1158/2159-8290.CD-11-0039", + "CorpusId": 27275016, "PubMed": "21984976"}, "corpusId": 27275016, "publicationVenue": + {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", "name": "Cancer Discovery", + "type": "journal", "alternate_names": ["Cancer Discov"], "issn": "2159-8274", + "url": "https://cancerdiscovery.aacrjournals.org/"}, "url": "https://www.semanticscholar.org/paper/3141ba16b8c5e721203a093cb2ea31360f584fb5", + "title": "High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer + elucidates a novel mechanism for regulation of PTEN protein stability.", "abstract": + "We demonstrate that phosphatidylinositol 3-kinase (PI3K) pathway aberrations + occur in >80% of endometrioid endometrial cancers, with coordinate mutations + of multiple PI3K pathway members being more common than predicted by chance. + PIK3R1 (p85\u03b1) mutations occur at a higher rate in endometrial cancer + than in any other tumor lineage, and PIK3R2 (p85\u03b2), not previously demonstrated + to be a cancer gene, is also frequently mutated. The dominant activation event + in the PI3K pathway appears to be PTEN protein loss. However, in tumors with + retained PTEN protein, PI3K pathway mutations phenocopy PTEN loss, resulting + in pathway activation. KRAS mutations are common in endometrioid tumors activating + independent events from PI3K pathway aberrations. Multiple PIK3R1 and PIK3R2 + mutations demonstrate gain of function, including disruption of a novel mechanism + of pathway regulation wherein p85\u03b1 dimers bind and stabilize PTEN. Taken + together, the PI3K pathway represents a critical driver of endometrial cancer + pathogenesis and a novel therapeutic target.", "venue": "Cancer Discovery", + "year": 2011, "referenceCount": 62, "citationCount": 410, "influentialCitationCount": + 24, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3187555?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-07-01", "journal": {"volume": + "1 2", "pages": "\n 170-85\n ", "name": "Cancer discovery"}, + "authors": [{"authorId": "50005741", "name": "L. W. Cheung"}, {"authorId": + "2030236", "name": "B. Hennessy"}, {"authorId": "2149869719", "name": "Jie + Li"}, {"authorId": "5875584", "name": "Shuangxing Yu"}, {"authorId": "6324437", + "name": "A. Myers"}, {"authorId": "120452446", "name": "B. Djordjevic"}, {"authorId": + "144004727", "name": "Yiling Lu"}, {"authorId": "1399421060", "name": "K. + Stemke\u2010Hale"}, {"authorId": "32111150", "name": "Mary D Dyer"}, {"authorId": + "2153304992", "name": "Fan Zhang"}, {"authorId": "152983291", "name": "Z. + Ju"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6757042", + "name": "S. Scherer"}, {"authorId": "67149842", "name": "Han Liang"}, {"authorId": + "8500699", "name": "K. Lu"}, {"authorId": "6416382", "name": "R. Broaddus"}, + {"authorId": "2241330", "name": "G. Mills"}]}, {"paperId": "320d7c4c80330560c8268088c72203bc20190def", + "externalIds": {"CorpusId": 55834815}, "corpusId": 55834815, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/320d7c4c80330560c8268088c72203bc20190def", + "title": "The PI3K regulatory subunit p85\u03b1 can exert tumor suppressor + properties through negative regulation of growth factor signalling", "abstract": + "PI3K plays a critical role in tumorigenesis and the PI3K p85 regulatory subunit + exerts both positive and negative effects on signaling. Expression of Pik3r1, + the gene encoding p85, is decreased in human prostate, lung, ovarian, bladder + and liver cancers consistent with the possibility that p85 has tumor suppressor + properties. We tested this hypothesis by studying mice with a liver-specific + deletion of the Pik3r1 gene. These mice exhibited enhanced insulin and growth + factor signaling and progressive changes in hepatic pathology, leading to + the development of aggressive hepatocellular carcinomas with pulmonary metastases. + Liver tumors that arose exhibited a markedly elevated level of phosphatidylinositol-3,4,5-trisphosphate + (PIP3), along with Akt activation and and decreased PTEN expression, at both + the mRNA and protein levels. Together, these results substantiate the concept + that the p85 subunit of PI3K has a tumor suppressive role in the liver and + possibly other tissues.", "venue": "", "year": 2011, "referenceCount": 49, + "citationCount": 3, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": null, "authors": + [{"authorId": "48311527", "name": "C. Taniguchi"}, {"authorId": "3687146", + "name": "J. Winnay"}, {"authorId": "16114256", "name": "Tatsuya Kondo"}, {"authorId": + "40803408", "name": "R. Bronson"}, {"authorId": "145030722", "name": "A. Guimaraes"}, + {"authorId": "47567005", "name": "J. Alem\u00e1n"}, {"authorId": "145954100", + "name": "Ji Luo"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}, {"authorId": + "91376400", "name": "Ralph"}, {"authorId": "30005093", "name": "Weissleder"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": + "C. Kahn"}]}, {"paperId": "33c6b78a39b9d30bbb2dfec8bc03ab5b9f783e66", "externalIds": + {"MAG": "2118390564", "DOI": "10.1158/2159-8274.CD-11-0049", "CorpusId": 34620184, + "PubMed": "22586302"}, "corpusId": 34620184, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/33c6b78a39b9d30bbb2dfec8bc03ab5b9f783e66", + "title": "The era of cancer discovery.", "abstract": "Realization of the need + for a forum that would bring basic and translational scientists and clinical + trials specialists together inspired the launch of Cancer Discovery .\n\nA + growing optimism that cancer research and treatment are entering a new era + is taking hold. Since the late 1950s, when the first real cancer cures were + achieved with combination therapies, progress in treating cancers has been + painfully slow, and with a few notable exceptions, breakthroughs came from + empirical observations in the clinic rather than from detailed understanding + of the disease. We did not understand why certain therapies were successful + in some subsets of cancers and failures in others. Most cancer drugs were + being developed on the basis of their ability to kill cancer cells grown on + plastic or in nude mice, with no real understanding of the mechanism of drug + action. It is therefore not surprising that the majority of these investigational + drugs ultimately failed when tested in large and expensive randomized trials, + and those that did succeed typically extended lives by only a few months. + In 1996, the 25th anniversary of the declaration of war on cancer, it was + difficult to point to a single breakthrough in treatment that emerged from + the tens of billions of dollars that had been spent on basic and clinical + research.\n\nNevertheless, we learned a lot during those first 25 years. We + discovered that cancer was, for the most part, caused by mutations in genes + (oncogenes) that control cell proliferation, cell growth, cell survival, and + cell differentiation. Importantly, we discovered that the types of cancers + that had been historically defined based on tissue of origin and classical + techniques of pathology could be further divided into dozens of subtypes when + analyzed at the molecular level. This knowledge began to explain why 2 patients + with the same disease diagnosis \u2026", "venue": "Cancer Discovery", "year": + 2011, "referenceCount": 0, "citationCount": 15, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Editorial"], "publicationDate": "2011-06-01", + "journal": {"volume": "1 1", "pages": "\n 1\n ", "name": "Cancer + discovery"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144806171", "name": "J. Baselga"}]}, {"paperId": "36c1bdaaa9b1ab8156e47ee3cc3f1a5bda2832ee", + "externalIds": {"MAG": "2135107959", "DOI": "10.1073/pnas.1107747108", "CorpusId": + 10121505, "PubMed": "21825134"}, "corpusId": 10121505, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/36c1bdaaa9b1ab8156e47ee3cc3f1a5bda2832ee", + "title": "Inhibition of PI3K binding to activators by serine phosphorylation + of PI3K regulatory subunit p85\u03b1 Src homology-2 domains", "abstract": + "Class IA PI3Ks are activated by growth factor receptors and generate lipid + second messengers that mediate downstream responses including cell growth, + cell migration, and cell survival. The p85 regulatory subunit of PI3K contains + Src homology-2 (SH2) domains that mediate binding to tyrosine-phosphorylated + receptors or adaptor proteins to facilitate localization and activation of + PI3K at the plasma membrane. We report here that persistent activation of + PKC family members by phorbol ester stimulation in cells leads to phosphorylation + of two serine residues at analogous sites on both SH2 domains of p85\u03b1 + (S361 and S652). The modified serine residues are located in the phospho-tyrosine + binding pockets of the two SH2 domains, and in the crystal structures the + phosphate moieties are predicted to occupy the same space as the phosphate + moieties of bound phospho-tyrosine peptides. Consistent with this prediction, + phosphorylation at these serine residues or mutation to aspartate inhibits + binding of p85\u03b1 to tyrosine-phosphorylated peptides. We provide evidence + that protein kinase D, which is phosphorylated and activated by PKCs, mediates + phosphorylation of S652 in the C-terminal SH2 domain. These results reveal + cross talk between PKC signaling and PI3K signaling that impairs PI3K pathway + activation under conditions of persistent PKC (and protein kinase D) activity.", + "venue": "Proceedings of the National Academy of Sciences", "year": 2011, + "referenceCount": 35, "citationCount": 77, "influentialCitationCount": 7, + "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/108/34/14157.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-08-08", "journal": {"volume": "108", "pages": "14157 + - 14162", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "46663676", "name": "Jennifer Y. Lee"}, {"authorId": "47591147", + "name": "Y. Chiu"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "370d9a009edf4cedd253c4e46dc82d541280e135", + "externalIds": {"CorpusId": 16821735}, "corpusId": 16821735, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/370d9a009edf4cedd253c4e46dc82d541280e135", + "title": "The Phosphoinositide 3-Kinase Regulatory Subunit p 85 Can Exert + Tumor Suppressor Properties through Negative Regulation of Growth Factor Signaling", + "abstract": "PI3K plays a critical role in tumorigenesis and the PI3K p85 + regulatory subunit exerts both positive and negative effects on signaling. + Expression of Pik3r1, the gene encoding p85, is decreased in human prostate, + lung, ovarian, bladder and liver cancers consistent with the possibility that + p85 has tumor suppressor properties. We tested this hypothesis by studying + mice with a liver-specific deletion of the Pik3r1 gene. These mice exhibited + enhanced insulin and growth factor signaling and progressive changes in hepatic + pathology, leading to the development of aggressive hepatocellular carcinomas + with pulmonary metastases. Liver tumors that arose exhibited a markedly elevated + level of phosphatidylinositol-3,4,5-trisphosphate (PIP3), along with Akt activation + and and decreased PTEN expression, at both the mRNA and protein levels. Together, + these results substantiate the concept that the p85 subunit of PI3K has a + tumor suppressive role in the liver and possibly other tissues.", "venue": + "", "year": 2011, "referenceCount": 50, "citationCount": 6, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "48311527", "name": "C. Taniguchi"}, + {"authorId": "3687146", "name": "J. Winnay"}, {"authorId": "16114256", "name": + "Tatsuya Kondo"}, {"authorId": "40803408", "name": "R. Bronson"}, {"authorId": + "145030722", "name": "A. Guimaraes"}, {"authorId": "47567005", "name": "J. + Alem\u00e1n"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": "1813278", + "name": "G. Stephanopoulos"}, {"authorId": "3127756", "name": "R. Weissleder"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": + "C. Kahn"}]}, {"paperId": "3bae8c5d4830756599569f6ced4969d6cf924053", "externalIds": + {"PubMedCentral": "3374201", "MAG": "2126524529", "DOI": "10.1186/1753-6561-6-S3-O15", + "CorpusId": 19806776, "PubMed": "21804546"}, "corpusId": 19806776, "publicationVenue": + {"id": "bb27e645-e57c-42c3-bcbc-c7b443c58209", "name": "Nature Genetics", + "type": "journal", "alternate_names": ["Nat Genet"], "issn": "1061-4036", + "url": "http://www.nature.com/ng/", "alternate_urls": ["http://www.nature.com/ng/index.html"]}, + "url": "https://www.semanticscholar.org/paper/3bae8c5d4830756599569f6ced4969d6cf924053", + "title": "Amplification of phosphoglycerate dehydrogenase diverts glycolytic + flux and contributes to oncogenesis", "abstract": null, "venue": "Nature Genetics", + "year": 2011, "referenceCount": 43, "citationCount": 915, "influentialCitationCount": + 36, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2011-09-01", "journal": {"volume": "6", "pages": "O15 - O15", "name": "BMC + Proceedings"}, "authors": [{"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "3785750", "name": "A. Grassian"}, {"authorId": "2318365", "name": + "R. Beroukhim"}, {"authorId": "145046418", "name": "M. Meyerson"}, {"authorId": + "145241228", "name": "G. Wagner"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "3471778", "name": "J. Brugge"}, {"authorId": "3804233", "name": + "M. V. Vander Heiden"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "41ba6b3fecec61f9a8b047cbe2bf0bf11c804341", "externalIds": {"MAG": "2011554530", + "DOI": "10.1016/j.cub.2010.12.047", "CorpusId": 17171239, "PubMed": "21256021"}, + "corpusId": 17171239, "publicationVenue": {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", + "name": "Current Biology", "type": "journal", "alternate_names": ["Curr Biology"], + "issn": "0960-9822", "url": "http://www.current-biology.com/", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/09609822"]}, "url": "https://www.semanticscholar.org/paper/41ba6b3fecec61f9a8b047cbe2bf0bf11c804341", + "title": "Cell-to-Cell Variability in PI3K Protein Level Regulates PI3K-AKT + Pathway Activity in Cell Populations", "abstract": null, "venue": "Current + Biology", "year": 2011, "referenceCount": 40, "citationCount": 103, "influentialCitationCount": + 3, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S096098221001715X/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-02-08", "journal": {"volume": + "21", "pages": "173-183", "name": "Current Biology"}, "authors": [{"authorId": + "40062987", "name": "T. Yuan"}, {"authorId": "31554501", "name": "G. Wulf"}, + {"authorId": "48793812", "name": "L. Burga"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "4a3b6f39f42c720cf78b9d8cb03cb3d17b2b5714", "externalIds": + {"MAG": "2810507926", "DOI": "10.3410/F.13411025.14782148", "CorpusId": 81829129}, + "corpusId": 81829129, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4a3b6f39f42c720cf78b9d8cb03cb3d17b2b5714", + "title": "Faculty Opinions recommendation of HIF-1 mediates the Warburg effect + in clear cell renal carcinoma.", "abstract": null, "venue": "", "year": 2011, + "referenceCount": 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2011-12-19", + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "5bd292075da0ce7f5a51a26ffb11310ed0cc79fc", + "externalIds": {"MAG": "2138383559", "DOI": "10.1126/scisignal.2001518", "CorpusId": + 13827655, "PubMed": "21386094"}, "corpusId": 13827655, "publicationVenue": + {"id": "c0efe552-8a0a-41a7-8ce2-340fb0dbfe6f", "name": "Science Signaling", + "type": "journal", "alternate_names": ["Sci Signal"], "issn": "1945-0877", + "url": "https://www.sciencemag.org/", "alternate_urls": ["https://stke.sciencemag.org/about/", + "https://stke.sciencemag.org/"]}, "url": "https://www.semanticscholar.org/paper/5bd292075da0ce7f5a51a26ffb11310ed0cc79fc", + "title": "Ubiquitination of K-Ras Enhances Activation and Facilitates Binding + to Select Downstream Effectors", "abstract": "Cancers in which K-Ras activation + drives tumor growth could be targeted by treatments blocking K-Ras ubiquitination. + Ubiquitination for Activity Mutational activation of the guanosine triphosphatase + (GTPase) Ras occurs frequently in various cancers. Although the three mammalian + isoforms\u2014N-Ras, H-Ras, and K-Ras\u2014couple to the same set of downstream + signaling pathways, mutations in each isoform are associated with different + types of cancers. In contrast to previous work showing that ubiquitination + of N-Ras and H-Ras restricts their activity, Sasaki et al. found that monoubiquitination + of Lys147 in K-Ras increased its activity and its ability to bind to downstream + effector proteins. Cells expressing the oncogenic G12V mutant of Ras form + tumors when injected into mice; however, cells expressing G12V Ras with an + additional mutation abolishing ubiquitination of Lys147 formed smaller tumors + in mice. Thus, cancers in which K-Ras activation drives tumor growth and survival + could be targeted by treatments blocking K-Ras ubiquitination. The accompanying + Perspective by Pfleger provides context on the distinct effects of ubiquitination + on the abundance, activity, and access to effectors of different Ras isoforms. + The guanosine triphosphate (GTP)\u2013loaded form of the guanosine triphosphatase + (GTPase) Ras initiates multiple signaling pathways by binding to various effectors, + such as the kinase Raf and phosphatidylinositol 3-kinase (PI3K). Ras activity + is increased by guanine nucleotide exchange factors that stimulate guanosine + diphosphate release and GTP loading and is inhibited by GTPase-activating + proteins that stimulate GTP hydrolysis. KRAS is the most frequently mutated + RAS gene in cancer. Here, we report that monoubiquitination of lysine-147 + in the guanine nucleotide\u2013binding motif of wild-type K-Ras could lead + to enhanced GTP loading. Furthermore, ubiquitination increased the binding + of the oncogenic Gly12Val mutant of K-Ras to the downstream effectors PI3K + and Raf. Thus, monoubiquitination could enhance GTP loading on K-Ras and increase + its affinity for specific downstream effectors, providing a previously unidentified + mechanism for Ras activation.", "venue": "Science Signaling", "year": 2011, + "referenceCount": 36, "citationCount": 154, "influentialCitationCount": 12, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3437993?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-03-08", "journal": {"volume": + "4", "pages": "ra13 - ra13", "name": "Science Signaling"}, "authors": [{"authorId": + "47742211", "name": "A. Sasaki"}, {"authorId": "6988610", "name": "A. Carracedo"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "46996935", "name": + "D. Anastasiou"}, {"authorId": "2775065", "name": "K. Takeuchi"}, {"authorId": + "4049626", "name": "E. Kahoud"}, {"authorId": "13971664", "name": "Sasson + Haviv"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "4499580", + "name": "P. Pandolfi"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "5e664f9c1ccd6e484bc5881ff5fd3a77e65ea040", "externalIds": {"MAG": "2517306124", + "CorpusId": 184894453}, "corpusId": 184894453, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/5e664f9c1ccd6e484bc5881ff5fd3a77e65ea040", + "title": "Table 5, SAR of selected tetrahydroquinoline-sulfonamides", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-03-03", "journal": null, + "authors": [{"authorId": "3275486", "name": "M. Boxer"}, {"authorId": "4084746", + "name": "Jian-Kang Jiang"}, {"authorId": "35413264", "name": "M. V. Heiden"}, + {"authorId": "145829790", "name": "M. Shen"}, {"authorId": "1799343", "name": + "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2148769632", + "name": "Craig J. Thomas"}]}, {"paperId": "60366e4b5a285d162ac697b0412664b542625635", + "externalIds": {"MAG": "2094399892", "DOI": "10.1126/science.1199484", "CorpusId": + 30224632, "PubMed": "21659605"}, "corpusId": 30224632, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/60366e4b5a285d162ac697b0412664b542625635", + "title": "Phosphoproteomic Analysis Identifies Grb10 as an mTORC1 Substrate + That Negatively Regulates Insulin Signaling", "abstract": "A search for substrates + of a growth-promoting kinase revealed a regulatory feedback loop involved + in tumor suppression. The evolutionarily conserved serine-threonine kinase + mammalian target of rapamycin (mTOR) plays a critical role in regulating many + pathophysiological processes. Functional characterization of the mTOR signaling + pathways, however, has been hampered by the paucity of known substrates. We + used large-scale quantitative phosphoproteomics experiments to define the + signaling networks downstream of mTORC1 and mTORC2. Characterization of one + mTORC1 substrate, the growth factor receptor\u2013bound protein 10 (Grb10), + showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback + inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal\u2013regulated, + mitogen-activated protein kinase (ERK-MAPK) pathways. Grb10 expression is + frequently down-regulated in various cancers, and loss of Grb10 and loss of + the well-established tumor suppressor phosphatase PTEN appear to be mutually + exclusive events, suggesting that Grb10 might be a tumor suppressor regulated + by mTORC1.", "venue": "Science", "year": 2011, "referenceCount": 17, "citationCount": + 651, "influentialCitationCount": 39, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3195509?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-06-10", "journal": {"volume": "332", "pages": "1322 + - 1326", "name": "Science"}, "authors": [{"authorId": "40508577", "name": + "Yonghao Yu"}, {"authorId": "6168327", "name": "Sang-Oh Yoon"}, {"authorId": + "4612853", "name": "G. Poulogiannis"}, {"authorId": "144785850", "name": "Qian + Yang"}, {"authorId": "50088305", "name": "X. Ma"}, {"authorId": "1705488", + "name": "J. Vill\u00e9n"}, {"authorId": "8429203", "name": "Neil Kubica"}, + {"authorId": "34846304", "name": "G. Hoffman"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2665934", "name": "S. Gygi"}, {"authorId": "4037343", + "name": "J. Blenis"}]}, {"paperId": "6525943ff6dcba1547fa65929b1b3f002c86e310", + "externalIds": {"MAG": "2339444939", "DOI": "10.1158/1538-7445.AM2011-LB-247", + "CorpusId": 87778108}, "corpusId": 87778108, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/6525943ff6dcba1547fa65929b1b3f002c86e310", + "title": "Mutation and functional analysis of PIK3CA and PIK3R1 in endometrial + cancer", "abstract": "The phosphatidylinositol 3 kinase (PI3K) pathway is + the most frequently activated pathway across multiple tumor lineages and this + is a potential therapeutic target. As a critical step to accelerate therapeutic + development in endometrial cancer, we performed a comprehensive analysis of + mutation and function of PI3K pathway members in a set of 243 highly characterized + endometrial tumors. Whole gene resequencing revealed the highest frequencies + of mutation in the PI3K pathway of any tumor lineage including PTEN (44%), + PIK3CA (40%; encoding the p110\u03b1 catalytic subunit of PI3K) and PIK3R1 + (20%; encoding the p85a regulatory subunit). Indeed, when complete protein + loss is considered, almost 80% of endometrioid endometrial cancers demonstrate + an aberration in the PI3K pathway. Remarkably, mutations in the PI3K pathway + were not mutually exclusive and indeed co-existence of PIK3CA or PIK3R1 mutation + with heterozygous PTEN mutation occurred at frequencies higher than predicted + by the frequency of each lesion alone. High-throughput reverse-phase protein + array suggested that the dominant signaling effects occurred with PTEN protein + loss and that PIK3CA or PIK3R1 mutation functionally mimic PTEN protein loss + as indicated by protein markers including phosphorylated Akt and stathmin. + Thus it appears likely that co-mutations in the PI3K pathway are selected + to compensate haploinsufficiency of PTEN due to PTEN heterozygous mutation. + To determine the functional consequences of mutations in PIK3R1, we demonstrated + that several somatic PIK3R1 mutations tested conferred cytokine-independent + growth on interleukin-3-dependent Ba/F3 cells and induced Akt phosphorylation + in endometrial cancer cell lines indicating that they were gain of function + mutations likely acting as oncogenes. Strikingly two of the gain of function + mutations (E160* and R348*) lacked the ability to bind to the p110 catalytic + subunit and E160* failed to bind to both p110 and PTEN. We demonstrate that + E160* disrupts a novel mechanism of pathway regulation wherein p85 binds and + stabilizes PTEN. Together, the data indicate that the PI3K pathway is targeted + in the vast majority of endometrioid endometrial cancers representing a novel + opportunity for implementation of targeted therapy. Citation Format: {Authors}. + {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of + the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia + (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-247. doi:10.1158/1538-7445.AM2011-LB-247", + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-04-15", "journal": {"volume": "71", "name": "Cancer Research"}, "authors": + [{"authorId": "50005741", "name": "L. W. Cheung"}, {"authorId": "2030236", + "name": "B. Hennessy"}, {"authorId": "2149869719", "name": "Jie Li"}, {"authorId": + "5875584", "name": "Shuangxing Yu"}, {"authorId": "6324437", "name": "A. Myers"}, + {"authorId": "120452446", "name": "B. Djordjevic"}, {"authorId": "144004727", + "name": "Yiling Lu"}, {"authorId": "1399421060", "name": "K. Stemke\u2010Hale"}, + {"authorId": "2153304992", "name": "Fan Zhang"}, {"authorId": "152983291", + "name": "Z. Ju"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "6757042", "name": "S. Scherer"}, {"authorId": "67149842", "name": "Han Liang"}, + {"authorId": "8500699", "name": "K. Lu"}, {"authorId": "152788293", "name": + "Broaddus R. Russell"}, {"authorId": "2241330", "name": "G. Mills"}]}, {"paperId": + "67ea0e4011c6558644aa076882f0b89b5fdd5325", "externalIds": {"MAG": "2004329237", + "DOI": "10.1158/2159-8290.CD-11-0061", "CorpusId": 8952786, "PubMed": "22116793"}, + "corpusId": 8952786, "publicationVenue": {"id": "de16002a-77c3-4d03-9348-5a1813238e0b", + "name": "Cancer Discovery", "type": "journal", "alternate_names": ["Cancer + Discov"], "issn": "2159-8274", "url": "https://cancerdiscovery.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/67ea0e4011c6558644aa076882f0b89b5fdd5325", + "title": "The APL paradigm and the \"co-clinical trial\" project.", "abstract": + "Tremendous advances in technologies have allowed the attainment of powerful + insights into the molecular and genetic determinants that drive human cancers. + However, this acquired knowledge has been translated into effective therapeutics + very slowly, in part due to difficulty in predicting which drug or drug combination + is likely to be effective in the complex mutational background of human cancers. + To address this difficulty we have proposed and initiated the \"co-clinical + trial\" project, in which we exploit mouse models that faithfully replicate + the variety of mutational events observed in human cancers, to conduct preclinical + trials that parallel ongoing human phase I/II clinical trials. Here, we focus + on concepts relevant to the application of this novel paradigm and the essential + components required for its implementation to ultimately achieve the rational + and rapid development of new therapeutic treatments.", "venue": "Cancer Discovery", + "year": 2011, "referenceCount": 33, "citationCount": 118, "influentialCitationCount": + 3, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3222327?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "2011-07-01", + "journal": {"volume": "1 2", "pages": "\n 108-16\n ", "name": + "Cancer discovery"}, "authors": [{"authorId": "3547827", "name": "C. Nardella"}, + {"authorId": "5729169", "name": "A. Lunardi"}, {"authorId": "40501341", "name": + "A. Patnaik"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4499580", "name": "P. Pandolfi"}]}, {"paperId": "6b2ffc9cbee8d421836061642643d9f1ccc676ff", + "externalIds": {"MAG": "1993989698", "DOI": "10.1101/sqb.2012.76.010900", + "CorpusId": 27702757, "PubMed": "22262476"}, "corpusId": 27702757, "publicationVenue": + {"id": "e24353f5-13a9-4d82-8e33-329cd22634a0", "name": "Cold Spring Harbor + Symposia on Quantitative Biology", "type": "journal", "alternate_names": ["Cold + Spring Harb Symp Quant Biology"], "issn": "0091-7451", "url": "https://www.cshlpress.com/", + "alternate_urls": ["http://symposium.cshlp.org/content/by/year", "http://symposium.cshlp.org/", + "http://symposium.cshlp.org/site/misc/index_archive.xhtml"]}, "url": "https://www.semanticscholar.org/paper/6b2ffc9cbee8d421836061642643d9f1ccc676ff", + "title": "Metabolic pathway alterations that support cell proliferation.", + "abstract": "Proliferating cells adapt metabolism to support the conversion + of available nutrients into biomass. How cell metabolism is regulated to balance + the production of ATP, metabolite building blocks, and reducing equivalents + remains uncertain. Proliferative metabolism often involves an increased rate + of glycolysis. A key regulated step in glycolysis is catalyzed by pyruvate + kinase to convert phosphoenolpyruvate (PEP) to pyruvate. Surprisingly, there + is strong selection for expression of the less active M2 isoform of pyruvate + kinase (PKM2) in tumors and other proliferative tissues. Cell growth signals + further decrease PKM2 activity, and cells with less active PKM2 use another + pathway with separate regulatory properties to convert PEP to pyruvate. One + consequence of using this alternative pathway is an accumulation of 3-phosphoglycerate + (3PG) that leads to the diversion of 3PG into the serine biosynthesis pathway. + In fact, in some cancers a substantial portion of the total glucose flux is + directed toward serine synthesis, and genetic evidence suggests that glucose + flux into this pathway can promote cell transformation. Environmental conditions + can also influence the pathways that cells use to generate biomass with the + source of carbon for lipid synthesis changing based on oxygen availability. + Together, these findings argue that distinct metabolic phenotypes exist among + proliferating cells, and both genetic and environmental factors influence + how metabolism is regulated to support cell growth.", "venue": "Cold Spring + Harbor Symposia on Quantitative Biology", "year": 2011, "referenceCount": + 43, "citationCount": 263, "influentialCitationCount": 14, "isOpenAccess": + true, "openAccessPdf": {"url": "http://symposium.cshlp.org/content/76/325.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": null, "journal": {"volume": + "76", "pages": "\n 325-34\n ", "name": "Cold Spring Harbor + symposia on quantitative biology"}, "authors": [{"authorId": "3804233", "name": + "M. V. Vander Heiden"}, {"authorId": "39089704", "name": "S. Lunt"}, {"authorId": + "40576003", "name": "T. Dayton"}, {"authorId": "8143199", "name": "B. Fiske"}, + {"authorId": "5553029", "name": "W. J. Israelsen"}, {"authorId": "6160202", + "name": "K. Mattaini"}, {"authorId": "8971766", "name": "N. Vokes"}, {"authorId": + "1813278", "name": "G. Stephanopoulos"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "2281284", "name": "C. Metallo"}, {"authorId": "2268976", + "name": "J. Locasale"}]}, {"paperId": "6cebb7a72591c4fee0d5a2b330c0701ee423e566", + "externalIds": {"MAG": "2009762318", "DOI": "10.4161/cc.10.22.18224", "CorpusId": + 21098011, "PubMed": "22064516"}, "corpusId": 21098011, "publicationVenue": + {"id": "1bce1796-d800-4a09-91e5-d3e3ed025037", "name": "Cell Cycle", "type": + "journal", "issn": "1551-4005", "url": "http://www.landesbioscience.com/journals/cc/", + "alternate_urls": ["http://www.tandfonline.com/loi/kccy20"]}, "url": "https://www.semanticscholar.org/paper/6cebb7a72591c4fee0d5a2b330c0701ee423e566", + "title": "Genetic selection for enhanced serine metabolism in cancer development", + "abstract": "Comment on: Locasale JW, et al. Nat Genet 2011; 43:869-74.", + "venue": "Cell Cycle", "year": 2011, "referenceCount": 0, "citationCount": + 36, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Editorial"], + "publicationDate": "2011-11-15", "journal": {"volume": "10", "pages": "3812 + - 3813", "name": "Cell Cycle"}, "authors": [{"authorId": "2268976", "name": + "J. Locasale"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "73e6f70f34d6ca5ba1a984bac26d02efc53138dd", "externalIds": {"MAG": "2289062540", + "DOI": "10.1016/j.bmcl.2011.08.114", "CorpusId": 13780824, "PubMed": "21958545"}, + "corpusId": 13780824, "publicationVenue": {"id": "56cde9e1-007e-4232-b5ea-ac20f55c39e8", + "name": "Bioorganic & Medicinal Chemistry Letters", "type": "journal", "alternate_names": + ["Bioorganic Med Chem Lett"], "issn": "0960-894X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/972/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/0960894X", + "https://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry"]}, + "url": "https://www.semanticscholar.org/paper/73e6f70f34d6ca5ba1a984bac26d02efc53138dd", + "title": "2-Oxo-N-aryl-1,2,3,4-tetrahydroquinoline-6-sulfonamides as activators + of the tumor cell specific M2 isoform of pyruvate kinase.", "abstract": null, + "venue": "Bioorganic & Medicinal Chemistry Letters", "year": 2011, "referenceCount": + 17, "citationCount": 54, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3224553?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-09-01", "journal": {"volume": "21 21", "pages": "\n 6322-7\n ", + "name": "Bioorganic & medicinal chemistry letters"}, "authors": [{"authorId": + "1699620778", "name": "M. Walsh"}, {"authorId": "2435894", "name": "K. Brimacombe"}, + {"authorId": "1799343", "name": "H. Veith"}, {"authorId": "15778492", "name": + "James M. Bougie"}, {"authorId": "144782742", "name": "T. Daniel"}, {"authorId": + "3802281", "name": "W. Leister"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5553029", "name": "W. J. Israelsen"}, {"authorId": "3804233", + "name": "M. V. Vander Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, + {"authorId": "2607088", "name": "D. Auld"}, {"authorId": "2148769632", "name": + "Craig J. Thomas"}, {"authorId": "3275486", "name": "M. Boxer"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '242694' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:44 GMT + Via: + - 1.1 3780d885214ffe62a324a7c3ec8567b0.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - ZhLGwVoT3vJvYP6xTTHddY1gGf76GafDMn5lyj0Tvn7-uN9uyi26lg== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOapHMpvHcFsIA= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '242694' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:44 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - a87237b9-9bd3-4dbf-a00e-20b53b1ca1d5 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=400&limit=100 + response: + body: + string: '{"offset": 400, "next": 500, "data": [{"paperId": "78d79be1f873972ad393761c85edd2997dd5c12d", + "externalIds": {"MAG": "2050966347", "DOI": "10.1158/1538-7445.AM2011-2808", + "CorpusId": 84891159}, "corpusId": 84891159, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/78d79be1f873972ad393761c85edd2997dd5c12d", + "title": "Abstract 2808: Characterization of KRAS rearrangements in metastatic + prostate cancer", "abstract": "Proceedings: AACR 102nd Annual Meeting 2011\u2010\u2010 + Apr 2\u20106, 2011; Orlando, FL\n\nIn this study, we employed a novel integrative + genomic-based approach to explore driving gene fusions contributing to the + progression of advanced prostate cancer. This method, called amplification + breakpoint ranking and assembly (ABRA), leverages the in vivo amplification + and breakpoint analysis in cancer cells to assemble novel gene fusions and + predict their tumorigenicity. Using ABRA, we nominated KRAS as a gene fusion + with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line- which + was originally derived from a metastatic prostate cancer to the brain. Interestingly, + analysis of tissues revealed that 2 out of 62 metastatic prostate cancers + harbored aberrations at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces + a chimerical protein which is readily ubiquitinated and relative instable, + whereas specific knock-down of the fusion attenuates cell invasion and xenograft + growth. Further, ectopic expression of the UBE2L3-KRAS fusion protein in NIH + 3T3 fibroblasts and RWPE prostate epithelial cells exhibits substantial transforming + activity in vitro and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates the + MEK/ERK pathway, which is commonly engaged by oncogenic mutant KRAS. Instead, + it enriches Ras proteins in late endosome, and diverts signaling to the AKT + and p38 MAPK pathways. While a number of oncogenic activating point mutations + of KRAS have been identified, this is the first description of a mutant chimeric + version of KRAS that is oncogenic and thus may represent a new class of cancer-related + alteration. This study also suggests that this aberration may drive metastatic + progression in a subset of prostate cancers, which may be targeted by anti-KRAS + therapies.\n\nCitation Format: {Authors}. {Abstract title} [abstract]. In: + Proceedings of the 102nd Annual Meeting of the American Association for Cancer + Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 + Suppl):Abstract nr 2808. doi:10.1158/1538-7445.AM2011-2808", "venue": "", + "year": 2011, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-04-15", "journal": {"volume": "71", "pages": "2808-2808", "name": "Cancer + Research"}, "authors": [{"authorId": "2107975065", "name": "Xiaosong Wang"}, + {"authorId": "39560950", "name": "Sunita Shankar"}, {"authorId": "3113892", + "name": "S. Dhanasekaran"}, {"authorId": "3913657", "name": "Bushra Ateeq"}, + {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "49737962", "name": + "X. Jing"}, {"authorId": "48706636", "name": "Daniel H. Robinson"}, {"authorId": + "144457382", "name": "Q. Cao"}, {"authorId": "4059774", "name": "A. Gopalan"}, + {"authorId": "30582790", "name": "V. Reuter"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "144014266", "name": "M. Rubin"}, {"authorId": + "145158003", "name": "N. Palanisamy"}, {"authorId": "6088770", "name": "S. + Varambally"}, {"authorId": "2186786", "name": "A. Chinnaiyan"}]}, {"paperId": + "7f05984e35474cfe410cce91b3aa540de3468dac", "externalIds": {"MAG": "2313737236", + "DOI": "10.1158/1538-7445.AM2011-956", "CorpusId": 88287914}, "corpusId": + 88287914, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7f05984e35474cfe410cce91b3aa540de3468dac", + "title": "Abstract 956: Receptor tyrosine kinases, not KRAS, activate PI3K + in KRAS mutant colorectal cancers", "abstract": "Proceedings: AACR 102nd Annual + Meeting 2011\u2010\u2010 Apr 2\u20106, 2011; Orlando, FL\n\nIntroduction: + Therapies inhibiting receptor tyrosine kinases (RTKs) are effective when they + lead to simultaneous downregulation of phosphoinositide 3-kinase (PI3K)-AKT + and mitogen-activated protein kinase (MEK)-ERK signaling. Although cetuximab + has demonstrated activity in KRAS wildtype cancers, it remains unknown if + RTK inhibition alone can suppress one or both of these pathways in colorectal + cancers, especially in cancers with KRAS mutations.\n\nExperimental Procedures + and Results: Colorectal cancer cells were treated with gefitinib (1 \u03bcM) + or Cetuximab (10 \u03bcg/mL) to compare the consequences of EGFR inhibition + on downstream signaling events between KRAS wt (n=6) and mt (n=8) cell lines. + In KRAS wt cancers, either cetuximab or gefitinib led to loss of ERK phosphorylation, + but had only a modest effect on PI3K signaling. However, in most KRAS mutant + cancers, EGFR inhibition minimally impacted ERK signaling and had neglible + effects on PI3K signaling. To determine if KRAS constitutively activates ERK + and PI3K signaling in KRAS mutant colorectal cancers, we utilized shRNA in + eight KRAS mutant cancer cell lines and abruptly turned off KRAS expression + in an vivo transgenic model. In all models, the phosphorylation of ERK was + markedly decreased by KRAS knockdown, but this was not associated with downregulation + of PI3K signaling. To determine how PI3K was activated in KRAS mutant cancers, + we immunoprecipitated the p85 regulatory subunit and identified that IRS proteins + co-precipitated with PI3K in KRAS mutant cancer. These complexes were disrupted + by an IGF-IR inhibitor, NVP-AEW541, but not by gefitinib, and accordingly, + NVP-AEW541 led to loss of AKT phosphorylation. Of the eight KRAS mutant cell + lines, we found p85/IRS-1 or p85/IRS-2 complexes in 7 cell lines. We also + observed that a monoclonal anti-IGF-IR antibody R1507 (18 mg/kg twice a week) + downregulated PI3K signaling in SW837 xenografts in vivo. Biochemical assessment + of patient specimens with KRAS mutations also suggested that PI3K was regulated + primarily by IGF-IR. Importantly, by combining RTK inhibitors with MEK inhibitors + in KRAS mutant cancers, both the PI3K and ERK pathways were concomitantly + downregulated leading to marked growth suppression and robust apoptosis. Furthermore, + combining R1507 (18 mg/kg twice a week) with a MEK inhibitor (AZD6244 25 mg/kg + twice daily) induced marked tumor regressions of a KRAS mutant colorectal + cancer in vivo.\n\nConclusions: In this study, we provide evidence that KRAS + does not drive PI3K signaling in KRAS mutant cancers, and demonstrate that + specific RTK inhibition potently suppresses PI3K signaling in vitro and in + vivo. These findings provide a framework for utilizing RTK inhibitors in the + treatment of KRAS mutant colorectal cancers.\n\nCitation Format: {Authors}. + {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of + the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia + (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 956. doi:10.1158/1538-7445.AM2011-956", + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-04-15", "journal": {"volume": "71", "pages": "956-956", "name": "Cancer + Research"}, "authors": [{"authorId": "1899940", "name": "H. Ebi"}, {"authorId": + "5956914", "name": "R. Corcoran"}, {"authorId": "153342143", "name": "Anurag + Singh"}, {"authorId": "1491946371", "name": "Zhao Chen"}, {"authorId": "4846062", + "name": "Youngchul Song"}, {"authorId": "144609942", "name": "E. Lifshits"}, + {"authorId": "2946715", "name": "D. Ryan"}, {"authorId": "3859322", "name": + "J. Meyerhardt"}, {"authorId": "1714039", "name": "C. Benes"}, {"authorId": + "88647391", "name": "J. Settleman"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "32596484", "name": "Kwok-Kin Wong"}, {"authorId": "6828387", + "name": "J. Engelman"}]}, {"paperId": "8155405e5acfca1dcc0b724eee83f0f9430de772", + "externalIds": {"MAG": "2312620101", "DOI": "10.1158/1538-7445.AM2011-5121", + "CorpusId": 74776458}, "corpusId": 74776458, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/8155405e5acfca1dcc0b724eee83f0f9430de772", + "title": "Abstract 5121: A targeted approach to identify activators of class + IA phosphoinositide-3-kinase in cancers using tandem mass spectrometry", "abstract": + "A majority of human cancers exhibit aberrant activation of the phosphoinositide + 3-Kinase (PI3K) pathway. In many cases this activation is due to mutations + or amplifications in upstream activators of PI3K resulting in activation by + direct binding of phosphotyrosine proteins (e.g., receptor tyrosine kinases + (RTK) or adaptors such as IRS-1/2 or Gab1/2) to the p85 regulatory subunit + of PI3K. To date, experiments to identify the mechanisms of PI3K activation + in cancer have remained difficult and cumbersome. Since inhibitors of many + of these RTKs are either already approved or in clinical trials, identification + of the major upstream activators of PI3K in a given tumor could suggest the + appropriate therapeutic intervention. Here we present a quantitative mass + spectrometry approach (targeted ion MS/MS \u2013 TIMM) for identifying the + upstream activators of PI3K in cancer cell lines grown on plastic as well + as in tumor Xenografts. Importantly, we show that in a series of non small + cell lung carcinoma cell lines, it is possible to predict the appropriate + drug for treating the cells based on the upstream activator of PI3K as revealed + by TIMM. Specifically, we identified how PI3K is activated in MET amplified, + EGFR and EML4-ALK driven non-small cell lung cancers (NSCLCs) both in vitro + and in vivo, and were successful in identifying the optimal RTK inhibitor + treatment for the H1703 NSCLC cell line. Additionally, this technology revealed + that TORC1 inhibition leads to activation of PI3K via IRS-2, not IRS-1 in + KRAS mutant cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. + In: Proceedings of the 102nd Annual Meeting of the American Association for + Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer + Res 2011;71(8 Suppl):Abstract nr 5121. doi:10.1158/1538-7445.AM2011-5121", + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-04-15", "journal": {"volume": "71", "pages": "5121-5121", "name": "Cancer + Research"}, "authors": [{"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6828387", "name": "J. Engelman"}]}, + {"paperId": "82307456412752c3701d7a4adc378a6662bceded", "externalIds": {"MAG": + "2508329323", "CorpusId": 99932392}, "corpusId": 99932392, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/82307456412752c3701d7a4adc378a6662bceded", + "title": "Figure 2, PBS Buffer Stability of NCGC00185916/CID-44543605", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-03-03", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "3275486", "name": "M. Boxer"}, + {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, {"authorId": + "1799343", "name": "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2148769632", "name": "Craig J. Thomas"}]}, {"paperId": "8233f48bd51990b9b6545798e2c793ec03e7925d", + "externalIds": {"MAG": "3018915888", "DOI": "10.3410/f.13411030.14782154", + "CorpusId": 223711066}, "corpusId": 223711066, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/8233f48bd51990b9b6545798e2c793ec03e7925d", + "title": "Faculty Opinions recommendation of Acetylation targets the M2 isoform + of pyruvate kinase for degradation through chaperone-mediated autophagy and + promotes tumor growth.", "abstract": null, "venue": "", "year": 2011, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://facultyopinions.com/download/13411030", + "status": null}, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-12-19", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "83516a169e8c70276efc7be9b262b53fb731a74f", "externalIds": {"MAG": + "2322629870", "DOI": "10.1158/1538-7445.AM2011-LB-255", "CorpusId": 86892367}, + "corpusId": 86892367, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/83516a169e8c70276efc7be9b262b53fb731a74f", + "title": "Abstract LB-255: A mass spectrometry platform to quantitatively + profile cancer cell metabolism from cells, tumors, and fixed tissue", "abstract": + "The metabolic requirements of cancer and proliferating cells are different + from that of normal differential tissue and may have diverse applications + in the treatment of cancers. However, many of the molecular mechanisms that + reorganize metabolism to support cell proliferation are unknown. To study + cancer cell metabolism, we implemented a mass spectrometry based platform + to quantitatively profile endogenous metabolites from proliferating cell lines, + tumor tissues and formalin fixed paraffin embedded (FFPE) tissue. Cell lines + are derived from several cancers including lung, multiple myeloma, prostate, + and gliobastoma (GBM). In some cases, these were compared to a drosophila + reference cell line. Patients were also profiled for disease classification + from their cerebrospinal fluid (CSF). We also were successful in extracting + polar metabolites from FFPE tissue more than five years old stored at room + temperature. For FFPE tissue samples, we show that we can observe differences + in disease states involving PI3K-TSC-TOR pathway and we compared different + extraction methods for acquiring metabolomics data from FFPE blocks. We show + that we can cluster GBM versus normal patients from analyzing their CSF. We + target more than 255 unique metabolites using selected reaction monitoring + (SRM) based analyses with an AB/Sciex 5500 QTRAP mass spectrometer coupled + to a Shimadzu UFLC using normal phase chromatography. For a single 18 min + run, our platform allows for unprecedented sensitivity, quantitation and coverage + of metabolites that comprise of diverse metabolic pathways from as little + as a single 6 cm tissue culture dish of cells or approximately 2\u20133 million + cells from tissue samples. We find that amide XBridge columns (Waters) at + 275 uL/min perform well in both negative and positive ion switching mode and + that the sampling rate of the instrument is sufficiently fast (cycle time + of 1.6 sec with 3 msec dwell times) to effectively capture up to 300 metabolite + targets without scheduled SRM runs. Peak areas of metabolites are integrated + using MultiQuant 1.1 software (Applied Biosystems). Peak areas from triplicate + runs are hierarchically clustered and statistical analyses are applied to + generate P values for metabolite changes over different biological conditions. + We also probed metabolic flux in pathways by targeting a set of 13C glucose + labeled metabolites. In addition, we have also analyzed a model cell line + after stimulation with Insulin and EGF to examine if growth factor induced + metabolic changes are evolutionarily conserved. Using metabolic inhibitors, + such as Iodoacetic acid, KCN, etc., we have been able to characterize the + consequences of inhibiting glycolysis and oxidative phosphorylation, respectively. + Finally, we considered kinase inhibitors and measured their effects on metabolism + in proliferating cancer cell lines. Citation Format: {Authors}. {Abstract + title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American + Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): + AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-255. doi:10.1158/1538-7445.AM2011-LB-255", + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-04-15", "journal": {"volume": "71", "name": "Cancer Research"}, "authors": + [{"authorId": "48520140", "name": "Xuemei Yang"}, {"authorId": "2268976", + "name": "J. Locasale"}, {"authorId": "49680398", "name": "R. Rahal"}, {"authorId": + "3739417", "name": "S. Breitkopf"}, {"authorId": "89152193", "name": "M. VanderHeiden"}, + {"authorId": "8663787", "name": "D. Spentzos"}, {"authorId": "48251343", "name": + "Chin-Lee Wu"}, {"authorId": "2001255", "name": "N. Perrimon"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "1913037", "name": "E. Wong"}, + {"authorId": "3028470", "name": "J. Asara"}]}, {"paperId": "8792f0b5d29918c5704d8fc26aed8926afad15ac", + "externalIds": {"MAG": "2512427951", "CorpusId": 100519416}, "corpusId": 100519416, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/8792f0b5d29918c5704d8fc26aed8926afad15ac", + "title": "Table 4, SAR of selected thieno[3,2-b]pyrrole[3,2-d]pyridazinones", + "abstract": null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-03-03", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "3275486", "name": "M. Boxer"}, + {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, {"authorId": + "1799343", "name": "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2148769632", "name": "Craig J. Thomas"}]}, {"paperId": "9773d7e86ac78e68c34d086a4dd228a8bbeb843d", + "externalIds": {"MAG": "2507977278", "CorpusId": 100232622}, "corpusId": 100232622, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9773d7e86ac78e68c34d086a4dd228a8bbeb843d", + "title": "Figure 3, PBS Buffer Stability of NCGC00186527/CID-44246498", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-03-03", "journal": null, + "authors": [{"authorId": "3275486", "name": "M. Boxer"}, {"authorId": "4084746", + "name": "Jian-Kang Jiang"}, {"authorId": "35413264", "name": "M. V. Heiden"}, + {"authorId": "145829790", "name": "M. Shen"}, {"authorId": "1799343", "name": + "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2148769632", + "name": "Craig J. Thomas"}]}, {"paperId": "9905df45a72f23d3db52911bce92a7a9d5710f08", + "externalIds": {"PubMedCentral": "3352081", "MAG": "2125669886", "DOI": "10.1098/rsob.110012", + "CorpusId": 215534261, "PubMed": "22645651"}, "corpusId": 215534261, "publicationVenue": + {"id": "5c640382-d1f2-4258-80f5-11f02570f2fc", "name": "Open Biology", "type": + "journal", "issn": "2046-2441", "url": "https://royalsocietypublishing.org/journal/rsob", + "alternate_urls": ["http://rsob.royalsocietypublishing.org/"]}, "url": "https://www.semanticscholar.org/paper/9905df45a72f23d3db52911bce92a7a9d5710f08", + "title": "Discovery of catalytically active orthologues of the Parkinson''s + disease kinase PINK1: analysis of substrate specificity and impact of mutations", + "abstract": "Missense mutations of the phosphatase and tensin homolog (PTEN)-induced + kinase 1 (PINK1) gene cause autosomal-recessive Parkinson''s disease. To date, + little is known about the intrinsic catalytic properties of PINK1 since the + human enzyme displays such low kinase activity in vitro. We have discovered + that, in contrast to mammalian PINK1, insect orthologues of PINK1 we have + investigated\u2014namely Drosophila melanogaster (dPINK1), Tribolium castaneum + (TcPINK1) and Pediculus humanus corporis (PhcPINK1)\u2014are active as judged + by their ability to phosphorylate the generic substrate myelin basic protein. + We have exploited the most active orthologue, TcPINK1, to assess its substrate + specificity and elaborated a peptide substrate (PINKtide, KKWIpYRRSPRRR) that + can be employed to quantify PINK1 kinase activity. Analysis of PINKtide variants + reveal that PINK1 phosphorylates serine or threonine, but not tyrosine, and + we show that PINK1 exhibits a preference for a proline at the +1 position + relative to the phosphorylation site. We have also, for the first time, been + able to investigate the effect of Parkinson''s disease-associated PINK1 missense + mutations, and found that nearly all those located within the kinase domain, + as well as the C-terminal non-catalytic region, markedly suppress kinase activity. + This emphasizes the crucial importance of PINK1 kinase activity in preventing + the development of Parkinson''s disease. Our findings will aid future studies + aimed at understanding how the activity of PINK1 is regulated and the identification + of physiological substrates.", "venue": "Open Biology", "year": 2011, "referenceCount": + 25, "citationCount": 91, "influentialCitationCount": 8, "isOpenAccess": true, + "openAccessPdf": {"url": "http://rsob.royalsocietypublishing.org/content/1/3/110012.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-11-01", "journal": {"volume": + "1", "name": "Open biology"}, "authors": [{"authorId": "6827525", "name": + "Helen I. Woodroof"}, {"authorId": "4742185", "name": "J. Pogson"}, {"authorId": + "69874482", "name": "M. Begley"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4206645", "name": "M. De\u00e1k"}, {"authorId": "144004440", + "name": "D. Campbell"}, {"authorId": "143949689", "name": "D. V. van Aalten"}, + {"authorId": "6049024", "name": "A. Whitworth"}, {"authorId": "3475566", "name": + "D. Alessi"}, {"authorId": "50684409", "name": "M. Muqit"}]}, {"paperId": + "9a1aec82181e0ea356cb11496a61482c3dcddd62", "externalIds": {"MAG": "2232391401", + "DOI": "10.1007/978-1-4419-9911-5_9", "CorpusId": 85976444}, "corpusId": 85976444, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9a1aec82181e0ea356cb11496a61482c3dcddd62", + "title": "AMP-Activated Protein Kinase and Cancer Cell Metabolism", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 111, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "pages": "193-211", "name": ""}, "authors": [{"authorId": "143918840", "name": + "B. Zheng"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "a34b686a799b9559d53d1a618c403d71801a1e90", "externalIds": {"MAG": "2465085905", + "CorpusId": 183596868}, "corpusId": 183596868, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/a34b686a799b9559d53d1a618c403d71801a1e90", + "title": "[Table, Probe Chemical Characterization].", "abstract": null, "venue": + "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Materials + Science"], "s2FieldsOfStudy": [{"category": "Materials Science", "source": + "external"}], "publicationTypes": null, "publicationDate": "2011-03-03", "journal": + {"volume": "", "name": ""}, "authors": [{"authorId": "3275486", "name": "M. + Boxer"}, {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": + "35413264", "name": "M. V. Heiden"}, {"authorId": "145829790", "name": "M. + Shen"}, {"authorId": "1799343", "name": "H. Veith"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "2148769632", "name": "Craig J. Thomas"}]}, + {"paperId": "ab63932f66167b1a720fd39193283bace5f82e68", "externalIds": {"CorpusId": + 54725771}, "corpusId": 54725771, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/ab63932f66167b1a720fd39193283bace5f82e68", + "title": "Quantitative Phosphoproteomic Analysis Identifies the Adaptor Protein + Grb 10 as an mTORC 1 Substrate that Negatively Regulates Insulin Signaling", + "abstract": "The evolutionarily conserved Ser-Thr kinase mTOR plays a critical + role in regulating many pathophysiological processes. Functional characterization + of the mTOR signaling pathways, however, has been hampered by the paucity + of known substrates. We used large-scale quantitative phospho-proteomics experiments + to define the signaling networks downstream of mTORC1 and mTORC2. Characterization + of one mTORC1 substrate, the growth factor receptor-bound protein 10 (Grb10), + showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback + inhibition of the phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated, + mitogen-activated protein kinase (ERK-MAPK) pathways. Grb10 expression is + frequently downregulated in various cancers, and loss of Grb10 and loss of + the well-established tumor suppressor phosphatase PTEN appear to be mutually + exclusive events, suggesting that Grb10 might be a tumor suppressor regulated + by mTORC1. The evolutionarily conserved Ser-Thr protein kinase mTOR functions + as the core catalytic component of two structurally and functionally distinct + signaling complexes. mTOR complex 1 (mTORC1) regulates protein translation, + autophagy and cell growth whereas mTOR complex 2 (mTORC2) regulates the actin + cytoskeleton and cell survival (1\u20133). mTORC1 and mTORC2 respond to upstream + inputs such as growth factors, energetic status, and amino acid levels (3) + but relatively few downstream targets of mTOR have been identified. Misregulated + mTOR activity is a common feature of most cancers (1) but clinical trials + evaluating the mTORC1 selective inhibitor rapamycin as an anti-cancer agent + have met with limited success (2). Rapamycin resistance has emerged as a major + challenge to its clinical use (4), and is caused in part by feedback loops + that activate the PI3K and ERK-MAPK signaling pathways in rapamycin treated + cells through poorly understood mechanisms (5, 6). Identifying substrates + of mTORC1 and mTORC2 will be important for understanding how mTOR signals + downstream, and for defining components of feedback loops involved in rapamycin + resistance. *To whom correspondence should be addressed. Steven_gygi@hms.harvard.edu + (S.P.G); john_blenis@hms.harvard.edu (J. B.). 4Current address, Department + of Cancer and Cell Biology, University of Cincinnati, College of Medicine, + Cincinnati, OH, 45267 5Current address, Department of Research Oncology Diagnostics, + Genentech Inc., 1 DNA Way, South San Francisco, CA, 94080 6Current address, + Department of Genome Sciences, University of Washington, Seattle, WA, 98195 + 7Current address, Developmental and Molecular Pathways, Novartis Institutes + for Biomedical Research, Cambridge, MA, 02139 NIH Public Access", "venue": + "", "year": 2011, "referenceCount": 0, "citationCount": 20, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "40508577", + "name": "Yonghao Yu"}, {"authorId": "6168327", "name": "Sang-Oh Yoon"}, {"authorId": + "4612853", "name": "G. Poulogiannis"}, {"authorId": "144785850", "name": "Qian + Yang"}, {"authorId": "50088305", "name": "X. Ma"}, {"authorId": "1705488", + "name": "J. Vill\u00e9n"}, {"authorId": "8429203", "name": "Neil Kubica"}, + {"authorId": "34846304", "name": "G. Hoffman"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2665934", "name": "S. Gygi"}, {"authorId": "4037343", + "name": "J. Blenis"}]}, {"paperId": "b0d2b1baac5a531e06ff01b1e1fec78a91b40548", + "externalIds": {"MAG": "2141240740", "DOI": "10.1038/emboj.2011.436", "CorpusId": + 734426, "PubMed": "22166995"}, "corpusId": 734426, "publicationVenue": {"id": + "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": "journal", + "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", "url": + "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/b0d2b1baac5a531e06ff01b1e1fec78a91b40548", + "title": "Human pluripotent stem cells decouple respiration from energy production", + "abstract": null, "venue": "EMBO Journal", "year": 2011, "referenceCount": + 10, "citationCount": 37, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3242981?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["LettersAndComments", "JournalArticle"], "publicationDate": "2011-12-14", + "journal": {"volume": "30", "name": "The EMBO Journal"}, "authors": [{"authorId": + "1397529716", "name": "Ng Shyh\u2010Chang"}, {"authorId": "1723564", "name": + "Yuxiang Zheng"}, {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "b4d12b89c8a3e23260c43349a843b736395ab1d7", + "externalIds": {"MAG": "2507756443", "CorpusId": 184627428}, "corpusId": 184627428, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/b4d12b89c8a3e23260c43349a843b736395ab1d7", + "title": "Table 1, Final optimized 1536-well assay protocol", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Computer Science"], "s2FieldsOfStudy": [{"category": "Computer + Science", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-03-03", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "3275486", "name": "M. Boxer"}, + {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, {"authorId": + "1799343", "name": "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2148769632", "name": "Craig J. Thomas"}]}, {"paperId": "b62cb441ccd0904cc047e895f250c648c0d7a58b", + "externalIds": {"MAG": "2038578974", "DOI": "10.1016/j.cmet.2011.03.006", + "CorpusId": 206837719, "PubMed": "21459332"}, "corpusId": 206837719, "publicationVenue": + {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", "name": "Cell Metabolism", + "type": "journal", "alternate_names": ["Cell Metab"], "issn": "1550-4131", + "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": ["http://www.sciencedirect.com/science/journal/15504131", + "http://www.cellmetabolism.org/"]}, "url": "https://www.semanticscholar.org/paper/b62cb441ccd0904cc047e895f250c648c0d7a58b", + "title": "A fluorescent reporter of AMPK activity and cellular energy stress.", + "abstract": null, "venue": "Cell Metabolism", "year": 2011, "referenceCount": + 39, "citationCount": 127, "influentialCitationCount": 12, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S1550413111000933/pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2011-04-06", "journal": + {"volume": "13 4", "pages": "\n 476-486\n ", "name": "Cell + metabolism"}, "authors": [{"authorId": "143971134", "name": "P. Tsou"}, {"authorId": + "143918840", "name": "B. Zheng"}, {"authorId": "5027028", "name": "Chia-Hsien + Hsu"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "bafaba286dd649d81592ab9cd40e677a1e1d4796", + "externalIds": {"MAG": "2122481965", "DOI": "10.1016/j.molcel.2011.08.030", + "CorpusId": 6847269, "PubMed": "22017875"}, "corpusId": 6847269, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/bafaba286dd649d81592ab9cd40e677a1e1d4796", + "title": "mTOR drives its own activation via SCF(\u03b2TrCP)-dependent degradation + of the mTOR inhibitor DEPTOR.", "abstract": null, "venue": "Molecules and + Cells", "year": 2011, "referenceCount": 45, "citationCount": 228, "influentialCitationCount": + 13, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276511007222/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-10-21", "journal": {"volume": + "44 2", "pages": "\n 290-303\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "7642679", "name": "Daming Gao"}, {"authorId": "4403700", + "name": "H. Inuzuka"}, {"authorId": "46699189", "name": "Mengyao Tan"}, {"authorId": + "50274365", "name": "H. Fukushima"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "3420906", "name": "Pengda Liu"}, {"authorId": "49048640", "name": + "L. Wan"}, {"authorId": "1859720", "name": "B. Zhai"}, {"authorId": "50611901", + "name": "Y. R. Chin"}, {"authorId": "39696512", "name": "Shavali Shaik"}, + {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "2665934", "name": + "S. Gygi"}, {"authorId": "145751285", "name": "A. Toker"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "143851342", "name": "J. Harper"}, {"authorId": "144084152", "name": "Wenyi + Wei"}]}, {"paperId": "bff6cc68ad806cde3886d5972f03bf9d3e2959d6", "externalIds": + {"MAG": "2110393953", "DOI": "10.1158/0008-5472.CAN-11-0445", "CorpusId": + 4970323, "PubMed": "21775521"}, "corpusId": 4970323, "publicationVenue": {"id": + "b0bd78b2-6591-460e-af71-196409b62e2c", "name": "Cancer Research", "type": + "journal", "alternate_names": ["Cancer Res"], "issn": "0008-5472", "url": + "https://cancerres.aacrjournals.org/", "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/bff6cc68ad806cde3886d5972f03bf9d3e2959d6", + "title": "Using tandem mass spectrometry in targeted mode to identify activators + of class IA PI3K in cancer.", "abstract": "Phosphatiditylinositide-3-kinase + (PI3K) is activated in some cancers by direct mutation, but it is activated + more commonly in cancer by mutation of upstream acting receptor tyrosine kinases + (TK). At present, there is no systematic method to determine which TK signaling + cascades activate PI3K in certain cancers, despite the likely utility of such + information to help guide selection of tyrosine kinase inhibitor (TKI) drug + strategies for personalized therapy. Here, we present a quantitative liquid + chromatography tandem mass spectrometry approach that identifies upstream + activators of PI3K both in vitro and in vivo. Using non-small cell lung carcinoma + to illustrate this approach, we show a correct identification of the mechanism + of PI3K activation in several models, thereby identifying the most appropriate + TKI to downregulate PI3K signaling. This approach also determined the molecular + mechanisms and adaptors required for PI3K activation following inhibition + of the mTOR kinase TORC1. We further validated the approach in breast cancer + cells with mutational activation of PIK3CA, where tandem mass spectrometry + detected and quantitatively measured the abundance of a helical domain mutant + (E545K) of PIK3CA connected to PI3K activation. Overall, our findings establish + a mass spectrometric approach to identify functional interactions that govern + PI3K regulation in cancer cells. Using this technique to define the pathways + that activate PI3K signaling in a given tumor could help inform clinical decision + making by helping guide personalized therapeutic strategies for different + patients.", "venue": "Cancer Research", "year": 2011, "referenceCount": 54, + "citationCount": 15, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "http://cancerres.aacrjournals.org/content/71/18/5965.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-09-15", "journal": {"volume": "71 18", "pages": "\n 5965-75\n ", + "name": "Cancer research"}, "authors": [{"authorId": "48520140", "name": "Xuemei + Yang"}, {"authorId": "4039016", "name": "Alexa B. Turke"}, {"authorId": "46315599", + "name": "J. Qi"}, {"authorId": "4846062", "name": "Youngchul Song"}, {"authorId": + "5162072", "name": "B. Rexer"}, {"authorId": "34988079", "name": "T. Miller"}, + {"authorId": "5984202", "name": "P. J\u00e4nne"}, {"authorId": "2057460", + "name": "C. Arteaga"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "6828387", "name": "J. Engelman"}, {"authorId": "3028470", "name": "J. Asara"}]}, + {"paperId": "c242b3e7618c27f4c0c89cc9db39523328bf1fdb", "externalIds": {"MAG": + "2515220964", "CorpusId": 113594604}, "corpusId": 113594604, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/c242b3e7618c27f4c0c89cc9db39523328bf1fdb", + "title": "Figure 8, Critical Workflow to Lead to in vivo studies of HPykM2 + activators", "abstract": null, "venue": "", "year": 2011, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Engineering"], "s2FieldsOfStudy": + [{"category": "Engineering", "source": "external"}], "publicationTypes": null, + "publicationDate": "2011-03-03", "journal": {"volume": "", "name": ""}, "authors": + [{"authorId": "3275486", "name": "M. Boxer"}, {"authorId": "4084746", "name": + "Jian-Kang Jiang"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "145829790", "name": "M. Shen"}, {"authorId": "1799343", "name": "H. Veith"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2148769632", + "name": "Craig J. Thomas"}]}, {"paperId": "c6840388ee0d73d08f80dcf00b38cc41d95fe281", + "externalIds": {"CorpusId": 17137963}, "corpusId": 17137963, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/c6840388ee0d73d08f80dcf00b38cc41d95fe281", + "title": "Using Departments of Pathology And", "abstract": "intRoDuction To + understand the characteristic features of driving gene fusions in cancer, + we previously carried out a large-scale integrative analysis of cancer genomic + datasets matched with gene rearrangement data (1). As part of this analysis, + we observed that in many instances a small subset of tumors or cancer cell + lines harboring an oncogenic gene fusion displays characteristic amplification + at the site of genomic rearrangement (refs. 2\u20136; Supplementary Fig. S1A + and B). Such amplifications usually affect a portion of the fusion gene and + are generally considered secondary genetic lesions associated with disease + progression, drug resistance, and poor prognosis (2, 4\u20138). In contrast, + high-level copy number changes that result in the marked overexpression of + oncogenes usually encompass the target genes at the center of overlapping + amplifications across a panel of tumor samples. Thus, a \u201cpartially\u201d + amplified cancer gene may suggest that this gene participates ReseARcH BRieF + JUNE 2011 CANCER DISCOVERY | 35 doi: 10.1158/2159-8274.CD-10-0022 \u00a92011 + American Association for Cancer Research. Cancer Research. on April 20, 2017. + \u00a9 2011 American Association for cancerdiscovery.aacrjournals.org Downloaded + from Published OnlineFirst April 3, 2011; DOI: 10.1158/2159-8274.CD-10-0022", + "venue": "", "year": 2011, "referenceCount": 29, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "48631932", + "name": "Xiao-Song Wang"}, {"authorId": "39560950", "name": "Sunita Shankar"}, + {"authorId": "3113892", "name": "S. Dhanasekaran"}, {"authorId": "3913657", + "name": "Bushra Ateeq"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": + "49737962", "name": "X. Jing"}, {"authorId": "48706636", "name": "Daniel H. + Robinson"}, {"authorId": "144457382", "name": "Q. Cao"}, {"authorId": "5608756", + "name": "John R. Prensner"}, {"authorId": "4221039", "name": "A. Yocum"}, + {"authorId": "2037452760", "name": "Rui Wang"}, {"authorId": "145571865", + "name": "Daniel F. Fries"}, {"authorId": "144202024", "name": "B. Han"}, {"authorId": + "6382794", "name": "I. Asangani"}, {"authorId": "152167434", "name": "Xuhong + Cao"}, {"authorId": "2154403330", "name": "Yong Li"}, {"authorId": "2716422", + "name": "G. Omenn"}, {"authorId": "5715823", "name": "D. Pflueger"}, {"authorId": + "4059774", "name": "A. Gopalan"}, {"authorId": "30582790", "name": "V. Reuter"}, + {"authorId": "4049626", "name": "E. Kahoud"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "144014266", "name": "M. Rubin"}, {"authorId": + "145158003", "name": "N. Palanisamy"}, {"authorId": "6088770", "name": "S. + Varambally"}, {"authorId": "2186786", "name": "A. Chinnaiyan"}]}, {"paperId": + "d12781afde75f3aa3083c3653d5d469b2df86294", "externalIds": {"MAG": "2164405838", + "DOI": "10.1042/BJ20110276", "CorpusId": 12583063, "PubMed": "21548880"}, + "corpusId": 12583063, "publicationVenue": {"id": "64838252-a209-4424-a778-3b86b4a83c48", + "name": "Biochemical Journal", "type": "journal", "alternate_names": ["Biochem + J"], "issn": "0264-6021", "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, + "url": "https://www.semanticscholar.org/paper/d12781afde75f3aa3083c3653d5d469b2df86294", + "title": "TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing + mutations on expression, activity, localization and development.", "abstract": + "Mutations that truncate the C-terminal non-catalytic moiety of TTBK2 (tau + tubulin kinase 2) cause the inherited, autosomal dominant, SCA11 (spinocerebellar + ataxia type\u00a011) movement disorder. In the present study we first assess + the substrate specificity of TTBK2 and demonstrate that it has an unusual + preference for a phosphotyrosine residue at the +2 position relative to the + phosphorylation site. We elaborate a peptide substrate (TTBKtide, RRKDLHDDEEDEAMSIYpA) + that can be employed to quantify TTBK2 kinase activity. Through modelling + and mutagenesis we identify a putative phosphate-priming groove within the + TTBK2 kinase domain. We demonstrate that SCA11 truncating mutations promote + TTBK2 protein expression, suppress kinase activity and lead to enhanced nuclear + localization. We generate an SCA11-mutation-carrying knockin mouse and show + that this leads to inhibition of endogenous TTBK2 protein kinase activity. + Finally, we find that, in homozygosity, the SCA11 mutation causes embryonic + lethality at embryonic day 10. These findings provide the first insights into + some of the intrinsic properties of TTBK2 and reveal how SCA11-causing mutations + affect protein expression, catalytic activity, localization and development. + We hope that these findings will be helpful for future investigation of the + regulation and function of TTBK2 and its role in SCA11.", "venue": "Biochemical + Journal", "year": 2011, "referenceCount": 24, "citationCount": 45, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3739326?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2011-07-01", "journal": {"volume": + "437 1", "pages": "\n 157-67\n ", "name": "The Biochemical + journal"}, "authors": [{"authorId": "6572211", "name": "M. Bouskila"}, {"authorId": + "6809445", "name": "Noor Esoof"}, {"authorId": "5740524", "name": "L. Gay"}, + {"authorId": "48043585", "name": "Emily Fang"}, {"authorId": "4206645", "name": + "M. De\u00e1k"}, {"authorId": "69874482", "name": "M. Begley"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2646124", "name": "A. Prescott"}, + {"authorId": "3917018", "name": "K. Storey"}, {"authorId": "3475566", "name": + "D. Alessi"}]}, {"paperId": "d17743cae27a10fc1a84da92bff397fcf461fa72", "externalIds": + {"MAG": "2516911901", "CorpusId": 185106799}, "corpusId": 185106799, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/d17743cae27a10fc1a84da92bff397fcf461fa72", + "title": "Table 3, SAR of selected N,N-bisarylsulfonamides", "abstract": null, + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Mathematics"], + "s2FieldsOfStudy": [{"category": "Mathematics", "source": "external"}, {"category": + "Mathematics", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-03-03", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "3275486", "name": "M. Boxer"}, {"authorId": "4084746", "name": "Jian-Kang + Jiang"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "145829790", + "name": "M. Shen"}, {"authorId": "1799343", "name": "H. Veith"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2148769632", "name": "Craig + J. Thomas"}]}, {"paperId": "d5e6a178c9d12a042bbba7fd5bb45029da7541db", "externalIds": + {"MAG": "1916946492", "DOI": "10.1111/j.1755-148X.2011.00919.x", "CorpusId": + 42241825, "PubMed": "21981974"}, "corpusId": 42241825, "publicationVenue": + {"id": "d4fab1a0-4b1b-43b8-a2e5-4d2a5d0dc3d6", "name": "Pigment Cell & Melanoma + Research", "type": "journal", "alternate_names": ["Pigment Cell Melanoma + Res"], "issn": "1755-1471", "url": "http://www.pigment.org/"}, "url": "https://www.semanticscholar.org/paper/d5e6a178c9d12a042bbba7fd5bb45029da7541db", + "title": "PHGDH amplification and altered glucose metabolism in human melanoma", + "abstract": "The metabolic requirements of cancer cells differ from that of + their normal counterparts. To support their proliferation, cancer cells switch + to a fermentative metabolism that is thought to support biomass production. + Instances where metabolic enzymes promote tumorigenesis remain rare. However, + an enzyme involved in the de novo synthesis of serine, 3\u2010phosphoglycerate + dehydrogenase (PHGDH), was recently identified as a putative oncogene. The + potential mechanisms by which PHGDH promotes cancer are discussed.", "venue": + "Pigment Cell & Melanoma Research", "year": 2011, "referenceCount": 33, "citationCount": + 115, "influentialCitationCount": 4, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "2011-12-01", "journal": {"volume": "24", "name": "Pigment + Cell & Melanoma Research"}, "authors": [{"authorId": "6424987", "name": "Edouard + Mullarky"}, {"authorId": "6160202", "name": "K. Mattaini"}, {"authorId": "3804233", + "name": "M. V. Vander Heiden"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2268976", "name": "J. Locasale"}]}, {"paperId": "d5e87e8391ac4798e14e9c6138610d18fc6a37e6", + "externalIds": {"MAG": "2511153834", "CorpusId": 99510790}, "corpusId": 99510790, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d5e87e8391ac4798e14e9c6138610d18fc6a37e6", + "title": "Figure 4, PBS Buffer Stability of NCGC00185939/CID-4547230", "abstract": + null, "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Materials Science"], "s2FieldsOfStudy": [{"category": "Materials + Science", "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-03-03", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "3275486", "name": "M. Boxer"}, + {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, {"authorId": + "1799343", "name": "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2148769632", "name": "Craig J. Thomas"}]}, {"paperId": "d9758f49728d9173fb1417c58decd4baaf7c065a", + "externalIds": {"MAG": "2028974980", "DOI": "10.1016/j.cmet.2011.07.014", + "CorpusId": 5150796, "PubMed": "21982705"}, "corpusId": 5150796, "publicationVenue": + {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", "name": "Cell Metabolism", + "type": "journal", "alternate_names": ["Cell Metab"], "issn": "1550-4131", + "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": ["http://www.sciencedirect.com/science/journal/15504131", + "http://www.cellmetabolism.org/"]}, "url": "https://www.semanticscholar.org/paper/d9758f49728d9173fb1417c58decd4baaf7c065a", + "title": "Metabolic flux and the regulation of mammalian cell growth.", "abstract": + null, "venue": "Cell Metabolism", "year": 2011, "referenceCount": 84, "citationCount": + 357, "influentialCitationCount": 16, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1550413111003457/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2011-10-05", "journal": {"volume": + "14 4", "pages": "\n 443-51\n ", "name": "Cell metabolism"}, + "authors": [{"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "e3d4b1b66d4c82e4b8d40327c943b20188a0be59", + "externalIds": {"CorpusId": 46937701}, "corpusId": 46937701, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/e3d4b1b66d4c82e4b8d40327c943b20188a0be59", + "title": "The Increasing Dominance of Teams in Production of Knowledge", "abstract": + ", 1036 (2007); 316 Science et al. Stefan Wuchty The Increasing Dominance + of Teams in Production of Knowledge This copy is for your personal, non-commercial + use only. clicking here. colleagues, clients, or customers by , you can order + high-quality copies for your If you wish to distribute this article to others + here. following the guidelines can be obtained by Permission to republish + or repurpose articles or portions of articles ): June 1, 2014 www.sciencemag.org + (this information is current as of The following resources related to this + article are available online at http://www.sciencemag.org/content/316/5827/1036.full.html + version of this article at: including high-resolution figures, can be found + in the online Updated information and services, http://www.sciencemag.org/content/suppl/2007/04/10/1136099.DC1.html + can be found at: Supporting Online Material http://www.sciencemag.org/content/316/5827/1036.full.html#related + found at: can be related to this article A list of selected additional articles + on the Science Web sites http://www.sciencemag.org/content/316/5827/1036.full.html#ref-list-1 + , 2 of which can be accessed free: cites 14 articles This article 70 article(s) + on the ISI Web of Science cited by This article has been http://www.sciencemag.org/content/316/5827/1036.full.html#related-urls + 73 articles hosted by HighWire Press; see: cited by This article has been + http://www.sciencemag.org/cgi/collection/sociology Sociology subject collections: + This article appears in the following", "venue": "", "year": 2011, "referenceCount": + 0, "citationCount": 320, "influentialCitationCount": 23, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Business", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": null, "authors": [{"authorId": "5610750", "name": "K. Zejnullahu"}, + {"authorId": "4441512", "name": "T. Mitsudomi"}, {"authorId": "121610638", + "name": "Youngchul Song"}, {"authorId": "40053421", "name": "Courtney Hyland"}, + {"authorId": "48490520", "name": "Joon-Oh Park"}, {"authorId": "3734755", + "name": "N. Lindeman"}, {"authorId": "77094637", "name": "Christopher-Michael + Gale"}, {"authorId": "2111027786", "name": "Xiaojun Zhao"}, {"authorId": "2054179920", + "name": "J. Christensen"}, {"authorId": "2638484", "name": "T. Kosaka"}, {"authorId": + "48115918", "name": "A. Holmes"}, {"authorId": "2056849769", "name": "A. M. + Rogers"}, {"authorId": "3740336", "name": "F. Cappuzzo"}, {"authorId": "17750315", + "name": "T. Mok"}, {"authorId": "2118593740", "name": "Charles Lee"}, {"authorId": + "2111408112", "name": "Bruce E. Johnson"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "e45b7d8040426d10d5d0afb970e29398aca9fe4e", "externalIds": + {"MAG": "2059019158", "DOI": "10.1016/j.molcel.2011.03.017", "CorpusId": 5171934, + "PubMed": "21474067"}, "corpusId": 5171934, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/e45b7d8040426d10d5d0afb970e29398aca9fe4e", + "title": "Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular + size.", "abstract": null, "venue": "Molecules and Cells", "year": 2011, "referenceCount": + 49, "citationCount": 245, "influentialCitationCount": 15, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276511002176/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Medicine", "source": "s2-fos-model"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-04-08", "journal": {"volume": "42 1", "pages": "\n 50-61\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "50149612", "name": "A. + Saci"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2972505", + "name": "C. Carpenter"}]}, {"paperId": "e58f4de259573ec03beef312bf66b4238221b599", + "externalIds": {"MAG": "2320941668", "DOI": "10.1158/1538-7445.AM2011-LB-418", + "CorpusId": 58321411}, "corpusId": 58321411, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/e58f4de259573ec03beef312bf66b4238221b599", + "title": "Abstract LB-418: Targeting the PI3K/mTOR pathway in genetically + engineered mouse models of prostate cancer", "abstract": "The PTEN and p53 + tumor suppressors are among the most commonly inactivated or mutated genes + in human cancer, including prostate cancer. Loss of PTEN is associated with + increased pathologic Gleason score and risk of clinical recurrence, and 20-60% + of human metastatic prostate cancers have loss of heterozygosity at the PTEN + locus, resulting in hyperactivation of the PI3K/mTOR pathway. Mice with germline + heterozygosity for PTEN have been shown to develop prostate intraepithelial + neoplasia (PIN) at a high rate (>60%) and mice with prostate specific homozygous + deletion of PTEN develop invasive prostate cancer, albeit with prolonged latency + of approx. 6 months. Combined inactivation of PTEN and p53 in mouse prostate + elicits invasive cancer by 9 weeks of age and invariable lethality by 7 months + of age. There are several PI3K pathway-directed therapies currently in Phase + I clinical trials, but the underlying tumor genetic signature of patients + most likely to respond to these therapies is largely unknown. To understand + the significance of targeting the PI3K/mTOR pathway in advanced prostate cancer + driven by PTEN +/\u2212 p53 loss, we evaluated the impact of GSK458 (a dual + PI3K/mTOR inhibitor) in prostate-specific PTEN/p53 double knockout mice and + prostate-specific PTEN-knockout mice. The mice were imaged by synchronized + 18 FDG-PET and T2-weighted MRI, respectively, for baseline tumor metabolic + and volumetric assessment prior to drug administration. GSK458 was administered + at 3 mg/kg by daily oral gavage for 3 weeks with serial 18 FDG-PET and T2-weighted + MRI imaging at 2 days, 1 week, 2 weeks and 3 weeks after initiation of treatment, + followed by sacrifice, prostate harvest and standard hisopathologic and immunohistochemical + staining. GSK458 treatment of PTEN/p53-deficient and PTEN-deficient mice results + in target inhibition, based on pharmacodynamic assessment by 18 FDG-PET uptake. + MRI and histopathologic analysis demonstrate that there is a significant reduction, + but not complete regression of tumor burden in both intraepithelial and poorly + differentiated atypical components within stroma and partial stromal collapse + following 3 weeks of GSK458 treatment. These data highlight the feasibility + of monitoring dual pharmacodynamics/antitumor effects of PI3K-directed therapies + using 18 FDG-PET/MRI imaging and underscore the utility of genetically engineered + mouse models to predict response to targeted therapies in genetically stratified + human clinical trials. The evaluation of PI3K-isoform specific inhibitors + and the design of rational combinations to overcome de novo and acquired resistance + mechanisms to PI3K-directed therapies are currently being explored in multiple + genetically engineered mouse model systems. Citation Format: {Authors}. {Abstract + title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American + Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): + AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-418. doi:10.1158/1538-7445.AM2011-LB-418", + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2011-04-15", "journal": {"volume": + "71", "name": "Cancer Research"}, "authors": [{"authorId": "40501341", "name": + "A. Patnaik"}, {"authorId": "13782167", "name": "K. Courtney"}, {"authorId": + "5679020", "name": "G. Bellinger"}, {"authorId": "3772950", "name": "E. Lunsford"}, + {"authorId": "40638403", "name": "K. Robichaud"}, {"authorId": "33624537", + "name": "A. Grant"}, {"authorId": "2177723", "name": "R. Lenkinski"}, {"authorId": + "3135556", "name": "I. Pedrosa"}, {"authorId": "7505152", "name": "S. Signoretti"}, + {"authorId": "46825918", "name": "R. Wooster"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "ed22246af3a264953ab2e9e6912256fa0a4a240a", "externalIds": + {"MAG": "2063082413", "DOI": "10.1158/1538-7445.AM2011-SY34-01", "CorpusId": + 84854706}, "corpusId": 84854706, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/ed22246af3a264953ab2e9e6912256fa0a4a240a", + "title": "Abstract SY34-01: Biomarkers for predicting response to PI3K inhibitors", + "abstract": "Proceedings: AACR 102nd Annual Meeting 2011\u2010\u2010 Apr 2\u20106, + 2011; Orlando, FL\n\nPhosphoinositide 3-kinase (PI 3-kinase) is a central + enzyme in a signaling pathway that mediates cellular responses to growth factors. + The pathway is highly conserved from worms and flies to humans and genetic + analysis of the pathway has revealed a conserved role in regulating glucose + metabolism, cell growth and organism longevity. Based on deletion of genes + encoding the catalytic or regulatory subunits of PI 3-kinase in the mouse, + PI 3-kinase mediates insulin-dependent regulation of glucose metabolism, and + defects in activation of this pathway result in insulin resistance and type + 2 diabetes. In contrast, mutational events that lead to hyperactivation of + PI 3-kinase result in cancers. Activating mutations in PIK3CA, encoding the + p110alpha catalytic subunit of PI 3-kinase or inactivating mutations in PTEN, + a phosphoinositide 3-phosphatases that reverses the effects of PI 3-kinase, + are among the most common events in solid tumors. We, and others have generated + mouse models in which a mutated form of the PIK3CA gene is expressed in a + tissue-specific and reversibly inducible manner. These mice develop cancers + that are dependent on continuous expression of the mutant PIK3CA gene. The + PIK3CA driven tumors are FDG-PET positive and turning off PI 3-kinase with + drugs results in an acute decline in FDG-PET signal that precedes tumor shrinkage. + These results suggest that the ability of PI 3-kinase to stimulate high rates + of glucose uptake and metabolism may be critical for the survival of PIK3CA + mutant tumors.\n\nCitation Format: {Authors}. {Abstract title} [abstract]. + In: Proceedings of the 102nd Annual Meeting of the American Association for + Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer + Res 2011;71(8 Suppl):Abstract nr SY34-01. doi:10.1158/1538-7445.AM2011-SY34-01", + "venue": "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-04-15", "journal": {"volume": "71", "name": "Cancer Research"}, "authors": + [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "f48a646988ffee21399639bef5d12b7ef86d529a", + "externalIds": {"MAG": "1506178278", "DOI": "10.1016/j.molcel.2011.11.005", + "CorpusId": 17520689, "PubMed": "22137581"}, "corpusId": 17520689, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/f48a646988ffee21399639bef5d12b7ef86d529a", + "title": "Chemical genetic screen for AMPK\u03b12 substrates uncovers a network + of proteins involved in mitosis.", "abstract": null, "venue": "Molecules and + Cells", "year": 2011, "referenceCount": 75, "citationCount": 220, "influentialCitationCount": + 15, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276511008550/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-12-01", "journal": {"volume": "44 6", "pages": "\n 878-92\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "3534122", "name": "M. + Banko"}, {"authorId": "3996589", "name": "J. Allen"}, {"authorId": "31358846", + "name": "B. Schaffer"}, {"authorId": "50693404", "name": "E. Wilker"}, {"authorId": + "143971134", "name": "P. Tsou"}, {"authorId": "144206424", "name": "Jamie + L. White"}, {"authorId": "1705488", "name": "J. Vill\u00e9n"}, {"authorId": + "2109253161", "name": "Beatrice T. Wang"}, {"authorId": "1508120753", "name": + "Sara R Kim"}, {"authorId": "152590916", "name": "K. Sakamoto"}, {"authorId": + "2665934", "name": "S. Gygi"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "88402408", "name": "M. Yaffe"}, {"authorId": "143818078", "name": + "K. Shokat"}, {"authorId": "47295224", "name": "A. Brunet"}]}, {"paperId": + "f54303976532e05b4f38d12a172130698faa60be", "externalIds": {"MAG": "2030733555", + "DOI": "10.1172/JCI57909", "CorpusId": 4969082, "PubMed": "21985784"}, "corpusId": + 4969082, "publicationVenue": {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", + "name": "Journal of Clinical Investigation", "type": "journal", "alternate_names": + ["J Clin Investig"], "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": + ["http://www.jci.org/", "https://www.jci.org/archive", "http://www.jci.org/impact"]}, + "url": "https://www.semanticscholar.org/paper/f54303976532e05b4f38d12a172130698faa60be", + "title": "Receptor tyrosine kinases exert dominant control over PI3K signaling + in human KRAS mutant colorectal cancers.", "abstract": "Therapies inhibiting + receptor tyrosine kinases (RTKs) are effective against some human cancers + when they lead to simultaneous downregulation of PI3K/AKT and MEK/ERK signaling. + However, mutant KRAS has the capacity to directly activate ERK and PI3K signaling, + and this is thought to underlie the resistance of KRAS mutant cancers to RTK + inhibitors. Here, we have elucidated the molecular regulation of both the + PI3K/AKT and MEK/ERK signaling pathways in KRAS mutant colorectal cancer cells + and identified combination therapies that lead to robust cancer cell apoptosis. + KRAS knockdown using shRNA suppressed ERK signaling in all of the human KRAS + mutant colorectal cancer cell lines examined. However, no decrease, and actually + a modest increase, in AKT phosphorylation was often seen. By performing PI3K + immunoprecipitations, we determined that RTKs, often IGF-IR, regulated PI3K + signaling in the KRAS mutant cell lines. This conclusion was also supported + by the observation that specific RTK inhibition led to marked suppression + of PI3K signaling and biochemical assessment of patient specimens. Interestingly, + combination of RTK and MEK inhibitors led to concomitant inhibition of PI3K + and MEK signaling, marked growth suppression, and robust apoptosis of human + KRAS mutant colorectal cancer cell lines in vitro and upon xenografting in + mice. These findings provide a framework for utilizing RTK inhibitors in the + treatment of KRAS mutant colorectal cancers.", "venue": "Journal of Clinical + Investigation", "year": 2011, "referenceCount": 58, "citationCount": 201, + "influentialCitationCount": 19, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.jci.org/articles/view/57909/files/pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2011-11-01", "journal": + {"volume": "121 11", "pages": "\n 4311-21\n ", "name": "The + Journal of clinical investigation"}, "authors": [{"authorId": "1899940", "name": + "H. Ebi"}, {"authorId": "5956914", "name": "R. Corcoran"}, {"authorId": "153342143", + "name": "Anurag Singh"}, {"authorId": "1491946371", "name": "Zhao Chen"}, + {"authorId": "4846062", "name": "Youngchul Song"}, {"authorId": "144609942", + "name": "E. Lifshits"}, {"authorId": "2946715", "name": "D. Ryan"}, {"authorId": + "3859322", "name": "J. Meyerhardt"}, {"authorId": "1714039", "name": "C. Benes"}, + {"authorId": "88647391", "name": "J. Settleman"}, {"authorId": "32596484", + "name": "Kwok-Kin Wong"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "6828387", "name": "J. Engelman"}]}, {"paperId": "f774644cf805bc0c4add320c02178d7c28368a49", + "externalIds": {"MAG": "2016535776", "DOI": "10.1126/science.1211485", "CorpusId": + 29899342, "PubMed": "22052977"}, "corpusId": 29899342, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/f774644cf805bc0c4add320c02178d7c28368a49", + "title": "Inhibition of Pyruvate Kinase M2 by Reactive Oxygen Species Contributes + to Cellular Antioxidant Responses", "abstract": "The glycolytic metabolism + of cancers differs from normal tissues, allowing tumor cells to survive under + oxidative stress. Control of intracellular reactive oxygen species (ROS) concentrations + is critical for cancer cell survival. We show that, in human lung cancer cells, + acute increases in intracellular concentrations of ROS caused inhibition of + the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys358. + This inhibition of PKM2 is required to divert glucose flux into the pentose + phosphate pathway and thereby generate sufficient reducing potential for detoxification + of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys358 + to Ser358 oxidation-resistant mutant exhibited increased sensitivity to oxidative + stress and impaired tumor formation in a xenograft model. Besides promoting + metabolic changes required for proliferation, the regulatory properties of + PKM2 may confer an additional advantage to cancer cells by allowing them to + withstand oxidative stress.", "venue": "Science", "year": 2011, "referenceCount": + 33, "citationCount": 965, "influentialCitationCount": 67, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3471535?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2011-11-01", "journal": {"volume": "334", "pages": "1278 + - 1283", "name": "Science"}, "authors": [{"authorId": "46996935", "name": + "D. Anastasiou"}, {"authorId": "4612853", "name": "G. Poulogiannis"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "3275486", "name": "M. Boxer"}, + {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "145829790", + "name": "M. Shen"}, {"authorId": "5679020", "name": "G. Bellinger"}, {"authorId": + "47742211", "name": "A. Sasaki"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "2607088", "name": "D. Auld"}, {"authorId": "2148769632", "name": + "Craig J. Thomas"}, {"authorId": "3804233", "name": "M. V. Vander Heiden"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "fb13058dbf5f65a98669bc2ff96f7012b44ec1a2", + "externalIds": {"MAG": "2902408540", "DOI": "10.3410/f.1383974.14782147", + "CorpusId": 92672560}, "corpusId": 92672560, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/fb13058dbf5f65a98669bc2ff96f7012b44ec1a2", + "title": "Faculty of 1000 evaluation for Q''s next: the diverse functions + of glutamine in metabolism, cell biology and cancer.", "abstract": null, "venue": + "", "year": 2011, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2011-12-19", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "06a531252a14f358a36fc664b45e454306489b62", + "externalIds": {"MAG": "2238925984", "DOI": "10.7490/F1000RESEARCH.413.1", + "CorpusId": 83230986}, "corpusId": 83230986, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/06a531252a14f358a36fc664b45e454306489b62", + "title": "A Mass Spectrometry Platform to Quantitatively Profile Cancer Cell + Metabolism from Cell Lines to Tissues.", "abstract": "RP-60 \n \nThe metabolic + requirements of cancer and proliferating cells are different from that of + normal differential tissue (the Warburg effect) and may have diverse applications + in the treatment of cancers and other neoplastic diseases. However, many of + the molecular mechanisms that conspire to reorganize metabolism to support + cell proliferation are unknown. To study the mechanisms of cancer cell metabolism, + we have implemented a mass spectrometry based platform to robustly quantitatively + profile endogenous metabolites from proliferating cell lines and tumor tissues + to extensively study cancer cell metabolism. Cell lines are derived from several + cancers including lung, multiple myeloma and prostate, as well as from a fast + proliferating Drosophila cell line. In addition, endogenous and Xenograft + tumor tissue from tumors such as prostate are profiled before and after drug + treatments. We routinely target nearly 250 metabolites using multiple reaction + monitoring (MRM) based analyses with an AB/Sciex 5500 QTRAP mass spectrometer + coupled to a Shimadzu UFLC using normal phase Hydrophilic interaction chromatography + (HILIC) at pH=9.0 with positive/negative switching within the same experimental + 25 minute LC/MS/MS run. For a single experiment, our platform allows for unprecedented + sensitivity, quantitation and coverage of metabolites that comprise of diverse + metabolic pathways from as little as a single 6 cm tissue culture dish of + cells or approximately 3 million cells from tissue samples. We find that 2.00mm + id x 10cm Luna NH2 HILIC columns (Phenomenex) at 250uL/min perform well in + both negative and positive ion mode and that the sampling rate of the instrument + is sufficiently fast to effectively capture up to 300 metabolite targets within + approximately a 20-25 minute gradient without the need for scheduled MRM runs + resulting in a cycle time of approximately 2 seconds with 5ms dwell times. + Peak areas of metabolites are integrated post run using MultiQuant 1.1 software + (Applied Biosystems). Peak areas from triplicate runs are then clustered using + hierarchical clustering and statistical analyses are applied in order to generate + P values for metabolite changes over different cellular conditions. We have + also carried out preliminary studies to probe flux in pathways by targeting + a set of 13C labeled metabolites from experiments where 13C labeled glucose + is added to cells. Using this platform, we have observed the metabolic effects + of growth factor signaling by analyzing metabolites from serum-starved versus + serum-fed cells derived from several cancers. We have also analyzed the metabolism + of a Drosophila model cell line after stimulation with Insulin and EGF (Spitz) + to examine if growth factor induced metabolic changes are evolutionarily conserved. + Using metabolic inhibitors, such as Iodoacetic acid and KCN, we have also + been able to characterize the consequences of inhibiting glycolysis and oxidative + phosphorylation, respectively. Finally, we considered a dual-pan PI3K/mTOR + catalytic site inhibitor and measured its effects on metabolism in a proliferating + breast epithelial cell line. In addition, we have profiled cerebral spinal + fluid (CSF) from gliobastoma (GBM) patients and noticed several metabolioc + profiles that are unique to GBM patients with mutated genes.", "venue": "", + "year": 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2010-08-13", "journal": {"volume": "21", "name": "Journal of biomolecular + techniques"}, "authors": [{"authorId": "48520140", "name": "Xuemei Yang"}, + {"authorId": "49680398", "name": "R. Rahal"}, {"authorId": "2268976", "name": + "J. Locasale"}, {"authorId": "9673009", "name": "S. Song"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "1913037", "name": "E. Wong"}, {"authorId": + "2001255", "name": "N. Perrimon"}, {"authorId": "35413264", "name": "M. V. + Heiden"}, {"authorId": "3028470", "name": "J. Asara"}]}, {"paperId": "0c385479fb72a13e819d76ef724eb50c05553a1a", + "externalIds": {"MAG": "2038424997", "DOI": "10.1042/BJ20090380", "CorpusId": + 36558141, "PubMed": "19857203"}, "corpusId": 36558141, "publicationVenue": + {"id": "64838252-a209-4424-a778-3b86b4a83c48", "name": "Biochemical Journal", + "type": "journal", "alternate_names": ["Biochem J"], "issn": "0264-6021", + "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, "url": + "https://www.semanticscholar.org/paper/0c385479fb72a13e819d76ef724eb50c05553a1a", + "title": "Development of an intracellularly acting inhibitory peptide selective + for PKN.", "abstract": "PKNs form a subfamily of the AGC serine/threonine + protein kinases, and have a catalytic domain homologous with that of PKC (protein + kinase C) in the C-terminal region and three characteristic ACC (antiparallel + coiled-coil) domain repeats in the N-terminal region. The preferred peptide + phosphorylation motif for PKNs determined by a combinatorial peptide library + method was highly similar to that of PKCs within a 10-amino-acid stretch. + Previously reported PKN inhibitory compounds also inhibit PKCs to a similar + extent, and no PKN selective inhibitors have been commercially available. + We have identified a 15-amino-acid peptide inhibitor of PKNs based on amino + acids 485-499 of the C-terminal region of the C2-like domain of PKN1. This + peptide, designated as PRL, selectively inhibits the kinase activity of all + isoforms of PKN (Ki=0.7 muM) towards a peptide substrate, as well as autophosphorylation + activity of PKN in vitro, in contrast with PKC. Reversible conjugation by + a disulfide bond of a carrier peptide bearing a penetration accelerating sequence + to PRL, facilitated the cellular uptake of this peptide and significantly + inhibited phosphorylation of tau by PKN1 at the PKN1-specific phosphorylation + site in vivo. This peptide may serve as a valuable tool for investigating + PKN activation and PKN-mediated responses.", "venue": "Biochemical Journal", + "year": 2010, "referenceCount": 62, "citationCount": 19, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3755880?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2010-01-15", "journal": {"volume": "425 2", "pages": "\n 445-53\n ", + "name": "The Biochemical journal"}, "authors": [{"authorId": "2074613771", + "name": "Kazuhiro Shiga"}, {"authorId": "8210553", "name": "Kentaro Takayama"}, + {"authorId": "3953054", "name": "S. Futaki"}, {"authorId": "6742227", "name": + "Jessica E. Hutti"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "32288616", "name": "K. Ueki"}, {"authorId": "47167461", "name": "Y. Ono"}, + {"authorId": "2463839", "name": "H. Mukai"}]}, {"paperId": "114d8e66a557f837bc8a25847410adb6c4f27f7b", + "externalIds": {"MAG": "2071759747", "DOI": "10.1158/1538-7445.AM10-34", "CorpusId": + 85201222}, "corpusId": 85201222, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/114d8e66a557f837bc8a25847410adb6c4f27f7b", + "title": "Abstract 34: Oncogenic tyrosine kinases phosphorylate and inhibit + PKM2 to provide a metabolic advantage to tumor growth", "abstract": "Proceedings: + AACR 101st Annual Meeting 2010\u2010\u2010 Apr 17\u201021, 2010; Washington, + DC\n\nCancer cells show increased aerobic glycolysis and enhanced lactate + production compared to healthy cells, a phenomenon known as the Warburg effect. + Cell surface growth factor receptors, which often carry tyrosine kinase activities + in their cytoplasmic domains, are overexpressed in many human cancers and + are believed to play a key role in determining cell metabolism. Thus, we explored + the hypothesis that tyrosine kinase signaling, which is commonly increased + in tumors, regulates the Warburg effect and contributes to tumorigenesis and + maintenance of the tumor.\n\nWe performed phospho-proteomics studies and found + that oncogenic forms of fibroblast growth factor (FGF) receptor type 1 (FGFR1) + inhibit the pyruvate kinase M2 isoform (PKM2) in cancer cells. Pyruvate kinase + is a rate-limiting enzyme during glycolysis and catalyzes the production of + pyruvate and ATP from phosphoenolpyruvate (PEP) and ADP. Recent studies demonstrated + that the enzymatic activity of the pyruvate kinase M2 isoform (PKM2) is inhibited + by phosphotyrosine binding; moreover, these researchers found that PKM2 is + crucial for aerobic glycolysis and provides a growth advantage to tumors. + However, it remains unclear which tyrosine kinase pathways are physiologically + responsible for this inhibition of PKM2 activity and which protein factors + undergo tyrosine phosphorylation, allowing them to bind to and thereby inhibit + PKM2. We found that PKM2 is itself tyrosine phosphorylated in cancer cells + and such a physiological modification of PKM2 promotes the switch to aerobic + glycolysis from oxidative phosphorylation. FGFR1 directly phosphorylates PKM2 + at tyrosine residue 105 (Y105). This inhibits the formation of active, tetrameric + PKM2 by disrupting binding of the PKM2 cofactor fructose-1,6-bisphosphate + (FBP). Moreover, we found that phosphorylation of PKM2 Y105 is common in human + cancers. Immunoblotting revealed that PKM2 is phosphorylated at Y105 in diverse + human breast cancer, lung cancer, prostate cancer and leukemia cell lines. + Oncogenic tyrosien kianses including BCR-ABL, FLT3-ITD and JAK2 also directly + phosphorylate PKM2 Y105 in in vitro kinase assays using purified proteins. + Furthermore, the presence of a PKM2 mutant in which phenylalanine is substituted + for Y105 (Y105F) in cancer cells leads to decreased cell proliferation under + hypoxic conditions, increased oxidative phosphorylation with reduced lactate + production, and reduced tumor growth in xenografts in nude mice.\n\nOur findings + suggest that tyrosine phosphorylation regulates PKM2 to provide a metabolic + advantage to tumor cells, thereby promoting tumor growth. This may represent + a common, short-term molecular mechanism underlying the Warburg effect in + both leukemias and solid tumors, in addition to the chronic changes believed + to be regulated by transcription factors, including hypoxia inducible factor + 1 and Myc.\n\nCitation Format: {Authors}. {Abstract title} [abstract]. In: + Proceedings of the 101st Annual Meeting of the American Association for Cancer + Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer + Res 2010;70(8 Suppl):Abstract nr 34.", "venue": "", "year": 2010, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2010-04-15", "journal": {"volume": + "70", "pages": "34-34", "name": "Cancer Research"}, "authors": [{"authorId": + "5648825", "name": "T. Hitosugi"}, {"authorId": "6357969", "name": "Sumin + Kang"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "2151016785", + "name": "Tae-Wook Chung"}, {"authorId": "4891579", "name": "S. Lonial"}, {"authorId": + "2108598823", "name": "Xu Wang"}, {"authorId": "32401310", "name": "G. Chen"}, + {"authorId": "143740055", "name": "Jianxin Xie"}, {"authorId": "40075084", + "name": "T. Gu"}, {"authorId": "4032764", "name": "R. Polakiewicz"}, {"authorId": + "6151924", "name": "J. Roesel"}, {"authorId": "3907849", "name": "T. Boggon"}, + {"authorId": "5531063", "name": "F. Khuri"}, {"authorId": "2246160", "name": + "D. Gilliland"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5224106", "name": "J. Kaufman"}, {"authorId": "5152140", "name": "J. Chen"}]}, + {"paperId": "13c26c21b7feeff49d9420445da524d35e8f54d6", "externalIds": {"MAG": + "2257121093", "CorpusId": 88164633}, "corpusId": 88164633, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/13c26c21b7feeff49d9420445da524d35e8f54d6", + "title": "Role of the PI 3-kinase signaling pathway in cell regulation and + human disease", "abstract": null, "venue": "", "year": 2010, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2010-11-30", "journal": null, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "1c92589ae4a6758b818e08792be4f07976e4080b", + "externalIds": {"CorpusId": 251597021}, "corpusId": 251597021, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/1c92589ae4a6758b818e08792be4f07976e4080b", + "title": "Characterization of PXK as a Protein Involved in Epidermal Growth + Factor Receptor Traf\ufb01cking (cid:1)", "abstract": "The phox homology (PX) + domain is a phosphoinositide-binding module that typically binds phosphatidyl- + inositol 3-phosphate. Out of 47 mammalian proteins containing PX domains, + more than 30 are denoted sorting nexins and several of these have been implicated + in internalization of cell surface proteins to the endosome, where phosphatidylinositol-3-phosphate + is concentrated. Here we investigated a multimodular protein termed PXK, composed + of a PX domain, a protein kinase-like domain, and a WASP homology 2 domain. + We show that the PX domain of PXK localizes this protein to the endosomal + membrane via binding to phosphatidylinositol 3-phosphate. PXK expression in + COS7 cells accelerated the ligand-induced internalization and degradation + of epidermal growth factor receptors by a mechanism requiring phosphatidylinositol + 3-phosphate binding but not involving the WASP homology 2 domain. Conversely, + depletion of PXK using RNA interference decreased the rate of epidermal growth + factor receptor internalization and degradation. Ubiquitination of epidermal + growth factor receptor by the ligand stimulation was enhanced in PXK-expressing + cells. These results indicate that PXK plays a critical role in epidermal + growth GST- FLAG-tagged PX domain cDNA PCR pEGFP-N1 PXK \ufb02uorescent protein + \ufb02uorescent protein (EYFP), HA-tagged wild-type mutant PXK subcloning + cDNA PX do- PXK subcloning corresponding cDNA PCR cDNAs amplify PXK and subcloned + into pEGFP-N1 vector. The constructs GST-fused proteins of the PX domain of + p40 phox (GST-p40 phox PX) and EGFP-FYVE3 have been described previously All + PXK mutants carrying one or two substitutions of amino acid residues were + produced using QuikChange site-directed mutagenesis All constructs were fully + sequenced to verify their integrity at the Beth Israel Deaconess Medical Center + DNA Sequencing Core Facility. More details of all constructs are on request.", + "venue": "", "year": 2010, "referenceCount": 76, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "46914940", + "name": "H. Takeuchi"}, {"authorId": "2115094818", "name": "Takako Takeuchi"}, + {"authorId": "2115556384", "name": "Jing Gao"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "144519906", "name": "M. Hirata"}]}, {"paperId": + "240f644722d188b80c54c48118679b49bea98704", "externalIds": {"MAG": "2166848534", + "DOI": "10.1073/pnas.1005642107", "CorpusId": 205248976, "PubMed": "20534477"}, + "corpusId": 205248976, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/240f644722d188b80c54c48118679b49bea98704", + "title": "A constitutively activated form of the p110\u03b2 isoform of PI3-kinase + induces prostatic intraepithelial neoplasia in mice", "abstract": "Recent + work has shown that ablation of p110\u03b2, but not p110\u03b1, markedly impairs + tumorigenesis driven by loss of phosphatase and tensin homolog (PTEN) in the + mouse prostate. Other laboratories have reported complementary data in human + prostate tumor lines, suggesting that p110\u03b2 activation is necessary for + tumorigenesis driven by PTEN loss. Given the multiple functions of PTEN, we + wondered if p110\u03b2 activation also is sufficient for tumorigenesis. Here, + we report that transgenic expression of a constitutively activated p110\u03b2 + allele in the prostate drives prostate intraepithelial neoplasia formation. + The resulting lesions are similar to, but are clearly distinct from, the ones + arising from PTEN loss or Akt activation. Array analyses of transcription + in multiple murine prostate tumor models featuring PI3K/AKT pathway activation + allowed construction of a pathway signature that may be useful in predicting + the prognosis of human prostate tumors.", "venue": "Proceedings of the National + Academy of Sciences", "year": 2010, "referenceCount": 62, "citationCount": + 57, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc2890726?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], + "publicationDate": "2010-06-01", "journal": {"volume": "107", "pages": "11002 + - 11007", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "2152572449", "name": "Sang Hyun Lee"}, {"authorId": "4612853", + "name": "G. Poulogiannis"}, {"authorId": "2411964", "name": "Saumyadipta Pyne"}, + {"authorId": "48143584", "name": "S. Jia"}, {"authorId": "2599871", "name": + "L. Zou"}, {"authorId": "7505152", "name": "S. Signoretti"}, {"authorId": + "6213932", "name": "M. Loda"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "6665338", "name": "T. Roberts"}]}, {"paperId": "2439e559caaf2918cf435879a72b69dfd5867ea0", + "externalIds": {"MAG": "1988097276", "DOI": "10.4161/CC.9.21.13925", "CorpusId": + 19530489, "PubMed": "21045562"}, "corpusId": 19530489, "publicationVenue": + {"id": "1bce1796-d800-4a09-91e5-d3e3ed025037", "name": "Cell Cycle", "type": + "journal", "issn": "1551-4005", "url": "http://www.landesbioscience.com/journals/cc/", + "alternate_urls": ["http://www.tandfonline.com/loi/kccy20"]}, "url": "https://www.semanticscholar.org/paper/2439e559caaf2918cf435879a72b69dfd5867ea0", + "title": "Rewiring of glycolysis in cancer cell metabolism", "abstract": "Comment + on: Vander Heiden MG, et al. Science 2010; 329:1492-9.", "venue": "Cell Cycle", + "year": 2010, "referenceCount": 0, "citationCount": 30, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.tandfonline.com/doi/pdf/10.4161/cc.9.21.13925?needAccess=true", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Editorial"], "publicationDate": "2010-11-01", "journal": {"volume": "9", + "pages": "4253 - 4253", "name": "Cell Cycle"}, "authors": [{"authorId": "2268976", + "name": "J. Locasale"}, {"authorId": "3804233", "name": "M. V. Vander Heiden"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "2e07af6def620ebec00412d700d45de7d1eb4ad1", + "externalIds": {"MAG": "1557882277", "CorpusId": 209613479}, "corpusId": 209613479, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/2e07af6def620ebec00412d700d45de7d1eb4ad1", + "title": "The Phosphoinositide 3-Kinase Regulatory Subunit p85 Can Exert Tumor + Suppressor Properties through Negative Regulation of Growth Factor Signaling", + "abstract": "Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, + and the PI3K p85 regulatory subunit exerts both positive and negative effects + on signaling. Expression of Pik3r1 , the gene encoding p85, is decreased in + human prostate, lung, ovarian, bladder, and liver cancers, consistent with + the possibility that p85 has tumor suppressor properties. We tested this hypothesis + by studying mice with a liver-specific deletion of the Pik3r1 gene. These + mice exhibited enhanced insulin and growth factor signaling and progressive + changes in hepatic pathology, leading to the development of aggressive hepatocellular + carcinomas with pulmonary metastases. Liver tumors that arose exhibited markedly + elevated levels of phosphatidylinositol (3,4,5)-trisphosphate, along with + Akt activation and decreased PTEN expression, at both the mRNA and protein + levels. Together, these results substantiate the concept that the p85 subunit + of PI3K has a tumor-suppressive role in the liver and possibly other tissues. + Cancer Res; 70(13); 5305 \u2013", "venue": "", "year": 2010, "referenceCount": + 55, "citationCount": 10, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2010-06-01", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "48311527", "name": "C. Taniguchi"}, + {"authorId": "3687146", "name": "J. Winnay"}, {"authorId": "16114256", "name": + "Tatsuya Kondo"}, {"authorId": "40803408", "name": "R. Bronson"}, {"authorId": + "145030722", "name": "A. Guimaraes"}, {"authorId": "47567005", "name": "J. + Alem\u00e1n"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": "1813278", + "name": "G. Stephanopoulos"}, {"authorId": "3127756", "name": "R. Weissleder"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": + "C. Kahn"}]}, {"paperId": "34bc4d15e1b1f97e8ccbf8bb2fd20407f06c202e", "externalIds": + {"MAG": "2780984082", "DOI": "10.1038/nature09132", "CorpusId": 4428604, "PubMed": + "20559394"}, "corpusId": 4428604, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/34bc4d15e1b1f97e8ccbf8bb2fd20407f06c202e", + "title": "Cancer-associated IDH1 mutations produce 2-hydroxyglutarate", "abstract": + null, "venue": "Nature", "year": 2010, "referenceCount": 1, "citationCount": + 193, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/nature09132.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "465", "pages": "966-966", + "name": "Nature"}, "authors": [{"authorId": "38799894", "name": "L. Dang"}, + {"authorId": "143657476", "name": "D. White"}, {"authorId": "144707828", "name": + "S. Gross"}, {"authorId": "36199097", "name": "B. Bennett"}, {"authorId": + "3564730", "name": "M. Bittinger"}, {"authorId": "4691854", "name": "E. Driggers"}, + {"authorId": "4936699", "name": "V. Fantin"}, {"authorId": "5240350", "name": + "H. G. Jang"}, {"authorId": "5210229", "name": "Shengfang Jin"}, {"authorId": + "46624965", "name": "M. Keenan"}, {"authorId": "145638995", "name": "K. Marks"}, + {"authorId": "2148693", "name": "R. Prins"}, {"authorId": "35327932", "name": + "P. Ward"}, {"authorId": "4886372", "name": "K. Yen"}, {"authorId": "5557307", + "name": "L. Liau"}, {"authorId": "35264286", "name": "J. Rabinowitz"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "31604076", "name": "C. Thompson"}, + {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "4297092", + "name": "S. Su"}]}, {"paperId": "393e3ea5c41b8d2d88cf0178687a3b6edbfb468b", + "externalIds": {"MAG": "2110134310", "DOI": "10.1126/scitranslmed.3001251", + "CorpusId": 206676697, "PubMed": "20826838"}, "corpusId": 206676697, "publicationVenue": + {"id": "1cd4baea-5ccc-4522-9dbf-0566f39d3b37", "name": "Science Translational + Medicine", "type": "journal", "alternate_names": ["Sci Transl Med"], "issn": + "1946-6234", "url": "https://stm.sciencemag.org/", "alternate_urls": ["https://stm.sciencemag.org/site/misc/about.xhtml"]}, + "url": "https://www.semanticscholar.org/paper/393e3ea5c41b8d2d88cf0178687a3b6edbfb468b", + "title": "Targeting a Common Collaborator in Cancer Development", "abstract": + "A small-molecule inhibitor of phosphatidylinositol 3-kinase enhances the + cytotoxic effects of the common chemotherapeutic agent doxorubicin in breast + and ovarian cancer cell lines. In this issue of Science Translational Medicine, + Wallin et al. have identified a subset of breast and ovarian cancer cell lines + that show synergistic response to the combination of doxorubicin and GDC-0941, + a class IA phosphatidylinositol 3-kinase (PI3K) inhibitor. Here, we discuss + the potential implications of these data on the clinical development of PI3K + pathway inhibitors as cancer therapeutics.", "venue": "Science Translational + Medicine", "year": 2010, "referenceCount": 54, "citationCount": 32, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3425950?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "LettersAndComments"], "publicationDate": "2010-09-08", + "journal": {"volume": "2", "pages": "48ps45 - 48ps45", "name": "Science Translational + Medicine"}, "authors": [{"authorId": "6324437", "name": "A. Myers"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "3c4c747325b8eee2f4d587842951431dbc8f4fd4", + "externalIds": {"CorpusId": 9137319}, "corpusId": 9137319, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/3c4c747325b8eee2f4d587842951431dbc8f4fd4", + "title": "Pr R moprevention Meets Glucose Control", "abstract": "wnloade report + by Memmott et al. (beginning on page 1066 in this issue of the journal) assessing + the efficacy antidiabetes drug metformin in a mouse model of lung carcinogenesis + suggests protective effects via ossible avenues: Decreased circulating insulin + and insulin-like growth factor levels and energy stress g to inhibition of + mammalian target of rapamycin signaling. These potential mechanisms are disleadin + cussed in this perspective, as are their implications for cancer prevention + and therapy. Cancer Prev Res; 3(9); 1049\u201352. \u00a92010 AACR.", "venue": + "", "year": 2010, "referenceCount": 46, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "103572289", "name": "Y. Engelman"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "406beec9864c052113713ba06b5025054940802f", + "externalIds": {"MAG": "2146042394", "DOI": "10.1158/1940-6207.CAPR-10-0178", + "CorpusId": 43822428, "PubMed": "20810671"}, "corpusId": 43822428, "publicationVenue": + {"id": "30248bd8-0140-4a2a-b2f7-d817cf173fdd", "name": "Cancer Prevention + Research", "type": "journal", "alternate_names": ["Cancer Prev Res"], "issn": + "1940-6215", "url": "https://cancerpreventionresearch.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/406beec9864c052113713ba06b5025054940802f", + "title": "Chemoprevention Meets Glucose Control", "abstract": "The report + by Memmott et al. (beginning on page 1066 in this issue of the journal) assessing + the efficacy of the antidiabetes drug metformin in a mouse model of lung carcinogenesis + suggests protective effects via two possible avenues: Decreased circulating + insulin and insulin-like growth factor levels and energy stress leading to + inhibition of mammalian target of rapamycin signaling. These potential mechanisms + are discussed in this perspective, as are their implications for cancer prevention + and therapy. Cancer Prev Res; 3(9); 1049\u201352. \u00a92010 AACR.", "venue": + "Cancer Prevention Research", "year": 2010, "referenceCount": 31, "citationCount": + 59, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "LettersAndComments"], "publicationDate": "2010-09-01", "journal": {"volume": + "3", "pages": "1049 - 1052", "name": "Cancer Prevention Research"}, "authors": + [{"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "43178192d84b1bcce32dadb8059a11124fe02f2b", "externalIds": + {"MAG": "2054668653", "DOI": "10.1016/S1359-6349(10)71748-1", "CorpusId": + 72809559}, "corpusId": 72809559, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/43178192d84b1bcce32dadb8059a11124fe02f2b", + "title": "43 Targeting PI3K: where are we?", "abstract": null, "venue": "", + "year": 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}], "publicationTypes": + null, "publicationDate": "2010-11-01", "journal": {"volume": "8", "pages": + "23", "name": "Ejc Supplements"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "45e4cd831750e7f8024683090632782817d76874", "externalIds": + {"MAG": "2017496419", "DOI": "10.1016/j.bmcl.2010.04.015", "CorpusId": 13777093, + "PubMed": "20451379"}, "corpusId": 13777093, "publicationVenue": {"id": "56cde9e1-007e-4232-b5ea-ac20f55c39e8", + "name": "Bioorganic & Medicinal Chemistry Letters", "type": "journal", "alternate_names": + ["Bioorganic Med Chem Lett"], "issn": "0960-894X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/972/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/0960894X", + "https://www.journals.elsevier.com/bioorganic-and-medicinal-chemistry"]}, + "url": "https://www.semanticscholar.org/paper/45e4cd831750e7f8024683090632782817d76874", + "title": "Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators + of the tumor cell specific M2 isoform of pyruvate kinase.", "abstract": null, + "venue": "Bioorganic & Medicinal Chemistry Letters", "year": 2010, "referenceCount": + 35, "citationCount": 104, "influentialCitationCount": 4, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2874658?pdf=render", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2010-06-01", "journal": {"volume": + "20 11", "pages": "\n 3387-93\n ", "name": "Bioorganic & medicinal + chemistry letters"}, "authors": [{"authorId": "4084746", "name": "Jian-Kang + Jiang"}, {"authorId": "3275486", "name": "M. Boxer"}, {"authorId": "3804233", + "name": "M. V. Vander Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, + {"authorId": "5914392", "name": "A. P. Skoumbourdis"}, {"authorId": "49134285", + "name": "Noel Southall"}, {"authorId": "1799343", "name": "H. Veith"}, {"authorId": + "3802281", "name": "W. Leister"}, {"authorId": "4066869", "name": "C. Austin"}, + {"authorId": "2117003935", "name": "H. Park"}, {"authorId": "3155966", "name": + "James Inglese"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2607088", "name": "D. Auld"}, {"authorId": "2148769632", "name": "Craig J. + Thomas"}]}, {"paperId": "496d78960822abfab3138b17da56ead8db445e82", "externalIds": + {"MAG": "2054339272", "DOI": "10.1158/1538-7445.AM10-33", "CorpusId": 85048723}, + "corpusId": 85048723, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/496d78960822abfab3138b17da56ead8db445e82", + "title": "Abstract 33: Cancer-associated IDH1 mutations produce 2-hydroxyglutarate", + "abstract": "Proceedings: AACR 101st Annual Meeting 2010\u2010\u2010 Apr 17\u201021, + 2010; Washington, DC\n\nMutations in the enzyme isocitrate dehydrogenase 1 + (IDH1) are a common feature of most gliomas and secondary glioblastomas, as + well as approx 10% acute myeloid leukemias. This event results in loss of + the enzyme''s ability to catalyze conversion of isocitrate to \u03b1 -ketoglutarate. + However, these mutations are all heterozygous and occur at a single amino + acid residue of the IDH1 active site consistent with an enzymatic gain of + function rather than a simple loss of function. To test this hypothesis we + characterized mutant IDH1 (IDH1m) biochemically. We have shown that cancer-associated + IDH1 mutations result in a new ability of the enzyme to catalyze the NADPH-dependent + reduction of \u03b1-ketoglutarate to R(-)-2-hydroxyglutarate (2-HG). Patients + with an inherited, neurometabolic disorders called 2-hydroxyglutaric aciduria + exhibit an accumulation of 2-HG in their CNS, and an increased risk of developing + malignant brain tumors. Similarly, in human malignant gliomas harboring IDH1 + mutations, we find elevated levels of 2-HG. Altogether our data demonstrate + that the IDH1 mutations result in production of 2-HG, and suggest that the + excess 2HG which accumulates in vivo contributes to the formation and malignant + progression of gliomas.\n\nCitation Format: {Authors}. {Abstract title} [abstract]. + In: Proceedings of the 101st Annual Meeting of the American Association for + Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; + Cancer Res 2010;70(8 Suppl):Abstract nr 33.", "venue": "", "year": 2010, "referenceCount": + 0, "citationCount": 3, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": "2010-04-15", "journal": {"volume": "70", "pages": "33-33", + "name": "Cancer Research"}, "authors": [{"authorId": "4936699", "name": "V. + Fantin"}, {"authorId": "38799894", "name": "L. Dang"}, {"authorId": "143657476", + "name": "D. White"}, {"authorId": "144707828", "name": "S. Gross"}, {"authorId": + "3564730", "name": "M. Bittinger"}, {"authorId": "4691854", "name": "E. Driggers"}, + {"authorId": "5240350", "name": "H. G. Jang"}, {"authorId": "5210229", "name": + "Shengfang Jin"}, {"authorId": "46624965", "name": "M. Keenan"}, {"authorId": + "145638995", "name": "K. Marks"}, {"authorId": "4886372", "name": "K. Yen"}, + {"authorId": "35327932", "name": "P. Ward"}, {"authorId": "2148693", "name": + "R. Prins"}, {"authorId": "5557307", "name": "L. Liau"}, {"authorId": "36199097", + "name": "B. Bennett"}, {"authorId": "35264286", "name": "J. Rabinowitz"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "31604076", "name": + "C. Thompson"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "4297092", "name": "S. Su"}]}, {"paperId": "4ab10117cbe2875f5f0515d32f82e228f95a10c5", + "externalIds": {"MAG": "2152445360", "DOI": "10.1073/pnas.0914845107", "CorpusId": + 24685399, "PubMed": "20133837"}, "corpusId": 24685399, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/4ab10117cbe2875f5f0515d32f82e228f95a10c5", + "title": "The alternative splicing repressors hnRNP A1/A2 and PTB influence + pyruvate kinase isoform expression and cell metabolism", "abstract": "Cancer + cells preferentially metabolize glucose by aerobic glycolysis, characterized + by increased lactate production. This distinctive metabolism involves expression + of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme + normally expressed in differentiated cells, and it confers a proliferative + advantage to tumor cells. The M1 and M2 pyruvate-kinase isozymes are expressed + from a single gene through alternative splicing of a pair of mutually exclusive + exons. We measured the expression of M1 and M2 mRNA and protein isoforms in + mouse tissues, tumor cell lines, and during terminal differentiation of muscle + cells, and show that alternative splicing regulation is sufficient to account + for the levels of expressed protein isoforms. We further show that the M1-specific + exon is actively repressed in cancer-cell lines\u2014although some M1 mRNA + is expressed in cell lines derived from brain tumors\u2014and demonstrate + that the related splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding + protein PTB, contribute to this control. Downregulation of these splicing + repressors in cancer-cell lines using shRNAs rescues M1 isoform expression + and decreases the extent of lactate production. These findings extend the + links between alternative splicing and cancer, and begin to define some of + the factors responsible for the switch to aerobic glycolysis.", "venue": "Proceedings + of the National Academy of Sciences", "year": 2010, "referenceCount": 32, + "citationCount": 375, "influentialCitationCount": 27, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.pnas.org/content/107/5/1894.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2010-01-19", "journal": {"volume": + "107", "pages": "1894 - 1899", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "14815404", "name": "C. V. Clower"}, + {"authorId": "145584048", "name": "D. Chatterjee"}, {"authorId": "47196879", + "name": "Zhenxun Wang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3804233", "name": "M. V. Vander Heiden"}, {"authorId": "2742032", "name": + "A. Krainer"}]}, {"paperId": "4f4e7cd92193b67dba2639f3f92de95a3288b67b", "externalIds": + {"MAG": "1965341570", "DOI": "10.1021/jm901577g", "CorpusId": 13795326, "PubMed": + "20017496"}, "corpusId": 13795326, "publicationVenue": {"id": "4cce60a8-2106-4240-bece-fb6488df6bd1", + "name": "Journal of Medicinal Chemistry", "type": "journal", "alternate_names": + ["J Med Chem"], "issn": "0022-2623", "url": "https://pubs.acs.org/journal/jmcmar", + "alternate_urls": ["http://pubs.acs.org/journal/jmcmar", "http://pubs.acs.org/journals/jmcmar/index.html"]}, + "url": "https://www.semanticscholar.org/paper/4f4e7cd92193b67dba2639f3f92de95a3288b67b", + "title": "Evaluation of substituted N,N''-diarylsulfonamides as activators + of the tumor cell specific M2 isoform of pyruvate kinase.", "abstract": "The + metabolism of cancer cells is altered to support rapid proliferation. Pharmacological + activators of a tumor cell specific pyruvate kinase isozyme (PKM2) may be + an approach for altering the classic Warburg effect characteristic of aberrant + metabolism in cancer cells yielding a novel antiproliferation strategy. In + this manuscript, we detail the discovery of a series of substituted N,N''-diarylsulfonamides + as activators of PKM2. The synthesis of numerous analogues and the evaluation + of structure-activity relationships are presented as well as assessments of + mechanism and selectivity. Several agents are found that have good potencies + and appropriate solubility for use as chemical probes of PKM2 including 55 + (AC(50) = 43 nM, maximum response = 84%; solubility = 7.3 microg/mL), 56 (AC(50) + = 99 nM, maximum response = 84%; solubility = 5.7 microg/mL), and 58 (AC(50) + = 38 nM, maximum response = 82%; solubility = 51.2 microg/mL). The small molecules + described here represent first-in-class activators of PKM2.", "venue": "Journal + of Medicinal Chemistry", "year": 2010, "referenceCount": 26, "citationCount": + 141, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc2818804?pdf=render", "status": + null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], + "publicationDate": "2010-02-11", "journal": {"volume": "53 3", "pages": "\n 1048-55\n ", + "name": "Journal of medicinal chemistry"}, "authors": [{"authorId": "3275486", + "name": "M. Boxer"}, {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": + "3804233", "name": "M. V. Vander Heiden"}, {"authorId": "145829790", "name": + "M. Shen"}, {"authorId": "5914392", "name": "A. P. Skoumbourdis"}, {"authorId": + "49134285", "name": "Noel Southall"}, {"authorId": "1799343", "name": "H. + Veith"}, {"authorId": "3802281", "name": "W. Leister"}, {"authorId": "4066869", + "name": "C. Austin"}, {"authorId": "2117003935", "name": "H. Park"}, {"authorId": + "3155966", "name": "James Inglese"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2607088", "name": "D. Auld"}, {"authorId": "2148769632", "name": + "Craig J. Thomas"}]}, {"paperId": "5cb4f3ce25d6eae9b1aacb9073c4946e02e7b855", + "externalIds": {"MAG": "2082410084", "DOI": "10.1016/j.bcp.2009.12.003", "CorpusId": + 45020461, "PubMed": "20005212"}, "corpusId": 45020461, "publicationVenue": + {"id": "c2ed7282-3d57-4734-ac70-51f9bffc1368", "name": "Biochemical Pharmacology", + "type": "journal", "alternate_names": ["Biochem Pharmacol"], "issn": "0006-2952", + "alternate_issns": ["1356-1839"], "url": "http://www.elsevier.com/locate/issn/00062952", + "alternate_urls": ["http://www.elsevier.com/wps/find/journaldescription.cws_home/525454/description", + "http://www.sciencedirect.com/science/journal/00062952"]}, "url": "https://www.semanticscholar.org/paper/5cb4f3ce25d6eae9b1aacb9073c4946e02e7b855", + "title": "Identification of small molecule inhibitors of pyruvate kinase M2.", + "abstract": null, "venue": "Biochemical Pharmacology", "year": 2010, "referenceCount": + 23, "citationCount": 227, "influentialCitationCount": 14, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2823991?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2010-04-15", "journal": {"volume": + "79 8", "pages": "\n 1118-24\n ", "name": "Biochemical pharmacology"}, + "authors": [{"authorId": "3804233", "name": "M. V. Vander Heiden"}, {"authorId": + "4164415", "name": "H. Christofk"}, {"authorId": "37745571", "name": "E. Schuman"}, + {"authorId": "6866092", "name": "Alexander O. Subtelny"}, {"authorId": "4536882", + "name": "H. Sharfi"}, {"authorId": "143686358", "name": "E. Harlow"}, {"authorId": + "13566176", "name": "Jun Xian"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "672d2ce11f6654613125b5b83e758289f3314949", "externalIds": {"MAG": + "2149161430", "DOI": "10.1158/0008-5472.CAN-09-3399", "CorpusId": 23377345, + "PubMed": "20530665"}, "corpusId": 23377345, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/672d2ce11f6654613125b5b83e758289f3314949", + "title": "The phosphoinositide 3-kinase regulatory subunit p85alpha can exert + tumor suppressor properties through negative regulation of growth factor signaling.", + "abstract": "Phosphoinositide 3-kinase (PI3K) plays a critical role in tumorigenesis, + and the PI3K p85 regulatory subunit exerts both positive and negative effects + on signaling. Expression of Pik3r1, the gene encoding p85, is decreased in + human prostate, lung, ovarian, bladder, and liver cancers, consistent with + the possibility that p85 has tumor suppressor properties. We tested this hypothesis + by studying mice with a liver-specific deletion of the Pik3r1 gene. These + mice exhibited enhanced insulin and growth factor signaling and progressive + changes in hepatic pathology, leading to the development of aggressive hepatocellular + carcinomas with pulmonary metastases. Liver tumors that arose exhibited markedly + elevated levels of phosphatidylinositol (3,4,5)-trisphosphate, along with + Akt activation and decreased PTEN expression, at both the mRNA and protein + levels. Together, these results substantiate the concept that the p85 subunit + of PI3K has a tumor-suppressive role in the liver and possibly other tissues.", + "venue": "Cancer Research", "year": 2010, "referenceCount": 53, "citationCount": + 114, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3204358?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2010-07-01", "journal": {"volume": "70 13", "pages": "\n 5305-15\n ", + "name": "Cancer research"}, "authors": [{"authorId": "48311527", "name": "C. + Taniguchi"}, {"authorId": "3687146", "name": "J. Winnay"}, {"authorId": "16114256", + "name": "Tatsuya Kondo"}, {"authorId": "40803408", "name": "R. Bronson"}, + {"authorId": "145030722", "name": "A. Guimaraes"}, {"authorId": "47567005", + "name": "J. Alem\u00e1n"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "1813278", "name": "G. Stephanopoulos"}, {"authorId": "3127756", "name": "R. + Weissleder"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144391716", "name": "C. Kahn"}]}, {"paperId": "69134a64931c2f2a499162757540cf8979f62f57", + "externalIds": {"CorpusId": 25459724}, "corpusId": 25459724, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/69134a64931c2f2a499162757540cf8979f62f57", + "title": "Rapidly Proliferating Cells Evidence for an Alternative Glycolytic + Pathway in", "abstract": ". clicking here colleagues, clients, or customers + by , you can order high-quality copies for your If you wish to distribute + this article to others . here following the guidelines can be obtained by + Permission to republish or repurpose articles or portions of articles (this + information is current as of September 20, 2010 ): The following resources + related to this article are available online at www.sciencemag.org http://www.sciencemag.org/cgi/content/full/329/5998/1492 + version of this article at: including high-resolution figures, can be found + in the online Updated information and services, http://www.sciencemag.org/cgi/content/full/329/5998/1492/DC1 + can be found at: Supporting Online Material http://www.sciencemag.org/cgi/content/full/329/5998/1492#otherarticles + , 8 of which can be accessed for free: cites 33 articles This article http://www.sciencemag.org/cgi/collection/cell_biol + Cell Biology : subject collections This article appears in the following", + "venue": "", "year": 2010, "referenceCount": 0, "citationCount": 88, "influentialCitationCount": + 10, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Business", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "6784962", "name": "K. Swanson"}, {"authorId": "4536882", "name": "H. Sharfi"}, + {"authorId": "6886706", "name": "G. Heffron"}, {"authorId": "1397671921", + "name": "D. Amador-Noguez"}, {"authorId": "4164415", "name": "H. Christofk"}, + {"authorId": "145241228", "name": "G. Wagner"}, {"authorId": "35264286", "name": + "J. Rabinowitz"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "6cb36fabb309de3a9d4466c32a149780ea2276db", + "externalIds": {"MAG": "988130218", "CorpusId": 82777837}, "corpusId": 82777837, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/6cb36fabb309de3a9d4466c32a149780ea2276db", + "title": "PTEN PATHWAYS & TARGETS", "abstract": null, "venue": "", "year": + 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}], "publicationTypes": + null, "publicationDate": "2010-03-01", "journal": {"volume": "", "name": ""}, + "authors": [{"authorId": "46748541", "name": "S. Baker"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4499580", "name": "P. Pandolfi"}, {"authorId": + "47689907", "name": "R. Parsons"}]}, {"paperId": "70878a703e97b15bc8a5afa8008a1048fce77c9c", + "externalIds": {"MAG": "2052771249", "DOI": "10.1126/scisignal.2000998", "CorpusId": + 39057842, "PubMed": "20736484"}, "corpusId": 39057842, "publicationVenue": + {"id": "c0efe552-8a0a-41a7-8ce2-340fb0dbfe6f", "name": "Science Signaling", + "type": "journal", "alternate_names": ["Sci Signal"], "issn": "1945-0877", + "url": "https://www.sciencemag.org/", "alternate_urls": ["https://stke.sciencemag.org/about/", + "https://stke.sciencemag.org/"]}, "url": "https://www.semanticscholar.org/paper/70878a703e97b15bc8a5afa8008a1048fce77c9c", + "title": "Akt\u2013RSK\u2013S6 Kinase Signaling Networks Activated by Oncogenic + Receptor Tyrosine Kinases", "abstract": "A phosphoproteomic analysis of signaling + pathways downstream of oncogenic receptor tyrosine kinases identified potential + therapeutic targets. Breaking a Deadly Addiction Most carcinomas are driven + by aberrant signaling from receptor tyrosine kinases (RTKs) and, indeed, may + become so dependent on these signals that they rely on them for survival. + The enormous complexity of the downstream pathways, however, and the sheer + numbers of potential targets, have made determining the substrates that mediate + this \u201concogene addiction\u201d a daunting task. Moritz et al. developed + a phosphoproteomic approach to identify targets of three core signaling pathways\u2014all + of which involve activation of AGC family kinases\u2014downstream of oncogenic + RTKs. They identified more than 300 phosphorylation targets of these signaling + pathways, including a set of proteins downstream of three different oncogenic + RTKs [c-Met, epidermal growth factor receptor (EGFR), and platelet-derived + growth factor receptor \u03b1 (PDGFR\u03b1)]. Moreover, they identified six + targets of RTK signaling whose knockdown affected cell viability. A detailed + analysis of one of these proteins\u2014the chaperone SGTA\u2014revealed a + role for it in stabilization of PDGFR\u03b1 and survival of cancer cells addicted + to PDGFR\u03b1 signaling. Receptor tyrosine kinases (RTKs) activate pathways + mediated by serine-threonine kinases, such as the PI3K (phosphatidylinositol + 3-kinase)\u2013Akt pathway, the Ras\u2013MAPK (mitogen-activated protein kinase)\u2013RSK + (ribosomal S6 kinase) pathway, and the mTOR (mammalian target of rapamycin)\u2013p70 + S6 pathway, that control important aspects of cell growth, proliferation, + and survival. The Akt, RSK, and p70 S6 family of protein kinases transmits + signals by phosphorylating substrates on an RxRxxS/T motif (R, arginine; S, + serine; T, threonine; and x, any amino acid). We developed a large-scale proteomic + approach to identify more than 300 substrates of this kinase family in cancer + cell lines driven by the c-Met, epidermal growth factor receptor (EGFR), or + platelet-derived growth factor receptor \u03b1 (PDGFR\u03b1) RTKs. We identified + a subset of proteins with RxRxxS/T sites for which phosphorylation was decreased + by RTK inhibitors (RTKIs), as well as by inhibitors of the PI3K, mTOR, and + MAPK pathways, and we determined the effects of small interfering RNA directed + against these substrates on cell viability. Phosphorylation of the protein + chaperone SGTA (small glutamine-rich tetratricopeptide repeat\u2013containing + protein \u03b1) at serine-305 was essential for PDGFR\u03b1 stabilization + and cell survival in PDGFR\u03b1-dependent cancer cells. Our approach provides + a new view of RTK and Akt\u2013RSK\u2013S6 kinase signaling, revealing previously + unidentified Akt\u2013RSK\u2013S6 kinase substrates that merit further consideration + as targets for combination therapy with RTKIs.", "venue": "Science Signaling", + "year": 2010, "referenceCount": 44, "citationCount": 293, "influentialCitationCount": + 20, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3137639?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2010-08-24", "journal": {"volume": + "3", "pages": "ra64 - ra64", "name": "Science Signaling"}, "authors": [{"authorId": + "47890210", "name": "A. Moritz"}, {"authorId": "47002721", "name": "Y. Li"}, + {"authorId": "49688792", "name": "A. Guo"}, {"authorId": "1705488", "name": + "J. Vill\u00e9n"}, {"authorId": "2154459653", "name": "Yi Wang"}, {"authorId": + "4804575", "name": "J. Macneill"}, {"authorId": "2269300", "name": "J. Kornhauser"}, + {"authorId": "46975075", "name": "K. Sprott"}, {"authorId": "2145786143", + "name": "Jing Zhou"}, {"authorId": "6536164", "name": "A. Possemato"}, {"authorId": + "48116069", "name": "J. Ren"}, {"authorId": "46627576", "name": "P. Hornbeck"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2665934", "name": + "S. Gygi"}, {"authorId": "1762119", "name": "J. Rush"}, {"authorId": "1756003", + "name": "M. Comb"}]}, {"paperId": "70e3782c102c70490ac8038dff212d0ac87dea85", + "externalIds": {"MAG": "100733775", "CorpusId": 68110415}, "corpusId": 68110415, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/70e3782c102c70490ac8038dff212d0ac87dea85", + "title": "Abstract 12839: Cardiac-Specific Deletion of RhoA Results in the + Development of Cardiac Hypertrophy via Effects on the Erk/MAPK and PI3K/Akt + pathways", "abstract": "Increased cardiac hypertrophy in response to pathological + stimuli can, over time, become decompensatory, leading to dilated cardiomyopathy + (DCM) and heart failure. Though several hypertrophic signa...", "venue": "", + "year": 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2010-11-23", "journal": {"volume": "122", "name": "Circulation"}, "authors": + [{"authorId": "40013703", "name": "P. Guha"}, {"authorId": "4328102", "name": + "A. Couvillon"}, {"authorId": "39988752", "name": "T. M. Marin"}, {"authorId": + "50403088", "name": "K. Keith"}, {"authorId": "50285364", "name": "Nina Mann"}, + {"authorId": "39514826", "name": "S. Choudhury"}, {"authorId": "2302010", + "name": "P. Kang"}, {"authorId": "144061154", "name": "A. Rosenzweig"}, {"authorId": + "2064407011", "name": "Christopher L. Carpenter"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "5806645", "name": "M. Kontaridis"}]}, + {"paperId": "727ea38d24c33bf3728c8dac321e433d80768ad2", "externalIds": {"MAG": + "2112313590", "DOI": "10.1128/MCB.01105-09", "CorpusId": 35649091, "PubMed": + "20086096"}, "corpusId": 35649091, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/727ea38d24c33bf3728c8dac321e433d80768ad2", + "title": "Characterization of PXK as a Protein Involved in Epidermal Growth + Factor Receptor Trafficking", "abstract": "ABSTRACT The phox homology (PX) + domain is a phosphoinositide-binding module that typically binds phosphatidylinositol + 3-phosphate. Out of 47 mammalian proteins containing PX domains, more than + 30 are denoted sorting nexins and several of these have been implicated in + internalization of cell surface proteins to the endosome, where phosphatidylinositol-3-phosphate + is concentrated. Here we investigated a multimodular protein termed PXK, composed + of a PX domain, a protein kinase-like domain, and a WASP homology 2 domain. + We show that the PX domain of PXK localizes this protein to the endosomal + membrane via binding to phosphatidylinositol 3-phosphate. PXK expression in + COS7 cells accelerated the ligand-induced internalization and degradation + of epidermal growth factor receptors by a mechanism requiring phosphatidylinositol + 3-phosphate binding but not involving the WASP homology 2 domain. Conversely, + depletion of PXK using RNA interference decreased the rate of epidermal growth + factor receptor internalization and degradation. Ubiquitination of epidermal + growth factor receptor by the ligand stimulation was enhanced in PXK-expressing + cells. These results indicate that PXK plays a critical role in epidermal + growth factor receptor trafficking through modulating ligand-induced ubiquitination + of the receptor.", "venue": "Molecular and Cellular Biology", "year": 2010, + "referenceCount": 76, "citationCount": 27, "influentialCitationCount": 3, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2838084?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2010-01-19", "journal": {"volume": + "30", "pages": "1689 - 1702", "name": "Molecular and Cellular Biology"}, "authors": + [{"authorId": "46914940", "name": "H. Takeuchi"}, {"authorId": "2115094818", + "name": "Takako Takeuchi"}, {"authorId": "2115556384", "name": "Jing Gao"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144519906", "name": + "M. Hirata"}]}, {"paperId": "791df30a33cd20a9875134af59c138ca4d1e6561", "externalIds": + {"MAG": "2071727216", "DOI": "10.1016/S1359-6349(10)71731-6", "CorpusId": + 72912698}, "corpusId": 72912698, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/791df30a33cd20a9875134af59c138ca4d1e6561", + "title": "27A Targeting the PI3K/mTOR pathway in genetically engineered mouse + models of advanced prostate cancer", "abstract": null, "venue": "", "year": + 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2010-11-01", "journal": {"volume": "8", "pages": "18-19", "name": "Ejc Supplements"}, + "authors": [{"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": "13782167", + "name": "K. Courtney"}, {"authorId": "7505152", "name": "S. Signoretti"}, + {"authorId": "6213932", "name": "M. Loda"}, {"authorId": "33624537", "name": + "A. Grant"}, {"authorId": "3135556", "name": "I. Pedrosa"}, {"authorId": "3772950", + "name": "E. Lunsford"}, {"authorId": "1788876", "name": "J. Frangioni"}, {"authorId": + "4499580", "name": "P. Pandolfi"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "7ad1bd3392c5f940ff6cf943c3470cbd3400b5ad", "externalIds": {"MAG": + "2146569590", "DOI": "10.1126/science.1188015", "CorpusId": 7314606, "PubMed": + "20847263"}, "corpusId": 7314606, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/7ad1bd3392c5f940ff6cf943c3470cbd3400b5ad", + "title": "Evidence for an Alternative Glycolytic Pathway in Rapidly Proliferating + Cells", "abstract": "Glucose Metabolism Revisited Cancer cells are revved + up to reproduce rapidly and typically consume glucose rapidly by glycolysis. + Why then do cancer cells express an isoform of a rate-limiting enzyme in glycolysis, + pyruvate kinase M2, which has decreased activity? Vander Heiden et al. (p. + 1492) propose that consequent accumulation of phosphoenolpyruvate, with the + help of an enzymatic activity that remains to be characterized, can lead to + phosphate transfer to phosphoglycerate mutase, another glycolytic enzyme, + providing the cell with a different way to make pyruvate. This may allow cancer + cells to produce pyruvate without generating excess adenosine triphosphate, + which can act through feedback to inhibit glycolyis. Characterization of cancer + cell metabolism provides evidence for a previously uncharacterized metabolic + pathway. Proliferating cells, including cancer cells, require altered metabolism + to efficiently incorporate nutrients such as glucose into biomass. The M2 + isoform of pyruvate kinase (PKM2) promotes the metabolism of glucose by aerobic + glycolysis and contributes to anabolic metabolism. Paradoxically, decreased + pyruvate kinase enzyme activity accompanies the expression of PKM2 in rapidly + dividing cancer cells and tissues. We demonstrate that phosphoenolpyruvate + (PEP), the substrate for pyruvate kinase in cells, can act as a phosphate + donor in mammalian cells because PEP participates in the phosphorylation of + the glycolytic enzyme phosphoglycerate mutase (PGAM1) in PKM2-expressing cells. + We used mass spectrometry to show that the phosphate from PEP is transferred + to the catalytic histidine (His11) on human PGAM1. This reaction occurred + at physiological concentrations of PEP and produced pyruvate in the absence + of PKM2 activity. The presence of histidine-phosphorylated PGAM1 correlated + with the expression of PKM2 in cancer cell lines and tumor tissues. Thus, + decreased pyruvate kinase activity in PKM2-expressing cells allows PEP-dependent + histidine phosphorylation of PGAM1 and may provide an alternate glycolytic + pathway that decouples adenosine triphosphate production from PEP-mediated + phosphotransfer, allowing for the high rate of glycolysis to support the anabolic + metabolism observed in many proliferating cells.", "venue": "Science", "year": + 2010, "referenceCount": 71, "citationCount": 531, "influentialCitationCount": + 23, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3030121?pdf=render", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Computer Science", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2010-09-01", "journal": {"volume": "329", "pages": "1492 - 1499", "name": + "Science"}, "authors": [{"authorId": "3804233", "name": "M. V. Vander Heiden"}, + {"authorId": "2268976", "name": "J. Locasale"}, {"authorId": "6784962", "name": + "K. Swanson"}, {"authorId": "4536882", "name": "H. Sharfi"}, {"authorId": + "6886706", "name": "G. Heffron"}, {"authorId": "1397671921", "name": "D. Amador-Noguez"}, + {"authorId": "4164415", "name": "H. Christofk"}, {"authorId": "145241228", + "name": "G. Wagner"}, {"authorId": "35264286", "name": "J. Rabinowitz"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "808b4eba03bbf952999adaabfff110dfcd4da0e7", "externalIds": {"MAG": + "2148420701", "PubMedCentral": "2892450", "DOI": "10.1186/1741-7007-8-88", + "CorpusId": 11874960, "PubMed": "20598111"}, "corpusId": 11874960, "publicationVenue": + {"id": "1617f5c3-5410-462d-91c9-7aa8ced2d91d", "name": "BMC Biology", "type": + "journal", "issn": "1741-7007", "url": "http://www.biomedcentral.com/1741-7007/", + "alternate_urls": ["http://www.biomedcentral.com/bmcbiol/", "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=215"]}, + "url": "https://www.semanticscholar.org/paper/808b4eba03bbf952999adaabfff110dfcd4da0e7", + "title": "Altered metabolism in cancer", "abstract": null, "venue": "BMC Biology", + "year": 2010, "referenceCount": 19, "citationCount": 147, "influentialCitationCount": + 11, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2010-06-25", "journal": {"volume": "8", "pages": "88 - 88", "name": "BMC + Biology"}, "authors": [{"authorId": "2268976", "name": "J. Locasale"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "82ae500805536ee0f9e7cfb62e39ee0c0f8b8183", + "externalIds": {"MAG": "1996926758", "DOI": "10.1073/pnas.1009941107", "CorpusId": + 24844395, "PubMed": "20696900"}, "corpusId": 24844395, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/82ae500805536ee0f9e7cfb62e39ee0c0f8b8183", + "title": "PARK2 deletions occur frequently in sporadic colorectal cancer and + accelerate adenoma development in Apc mutant mice", "abstract": "In 100 primary + colorectal carcinomas, we demonstrate by array comparative genomic hybridization + (aCGH) that 33% show DNA copy number (DCN) loss involving PARK2, the gene + encoding PARKIN, the E3 ubiquitin ligase whose deficiency is responsible for + a form of autosomal recessive juvenile parkinsonism. PARK2 is located on chromosome + 6 (at 6q25\u201327), a chromosome with one of the lowest overall frequencies + of DNA copy number alterations recorded in colorectal cancers. The PARK2 deletions + are mostly focal (31% \u223c0.5 Mb on average), heterozygous, and show maximum + incidence in exons 3 and 4. As PARK2 lies within FRA6E, a large common fragile + site, it has been argued that the observed DCN losses in PARK2 in cancer may + represent merely the result of enforced replication of locally vulnerable + DNA. However, we show that deficiency in expression of PARK2 is significantly + associated with adenomatous polyposis coli (APC) deficiency in human colorectal + cancer. Evidence of some PARK2 mutations and promoter hypermethylation is + described. PARK2 overexpression inhibits cell proliferation in vitro. Moreover, + interbreeding of Park2 heterozygous knockout mice with ApcMin mice resulted + in a dramatic acceleration of intestinal adenoma development and increased + polyp multiplicity. We conclude that PARK2 is a tumor suppressor gene whose + haploinsufficiency cooperates with mutant APC in colorectal carcinogenesis.", + "venue": "Proceedings of the National Academy of Sciences", "year": 2010, + "referenceCount": 49, "citationCount": 202, "influentialCitationCount": 13, + "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/107/34/15145.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2010-08-09", "journal": {"volume": + "107", "pages": "15145 - 15150", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "4612853", "name": "G. Poulogiannis"}, + {"authorId": "1852968", "name": "R. McIntyre"}, {"authorId": "49235150", "name": + "M. Dimitriadi"}, {"authorId": "6683881", "name": "J. Apps"}, {"authorId": + "2841675", "name": "Catherine H. Wilson"}, {"authorId": "4040402", "name": + "K. Ichimura"}, {"authorId": "48784567", "name": "F. Luo"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "2184292", "name": "A. Wyllie"}, {"authorId": + "145669576", "name": "D. Adams"}, {"authorId": "118353344", "name": "M. Arends"}]}, + {"paperId": "8851d6e9d18610713205e84c3cfb972d21ee8f72", "externalIds": {"MAG": + "2493822482", "CorpusId": 89179986}, "corpusId": 89179986, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/8851d6e9d18610713205e84c3cfb972d21ee8f72", + "title": "Figure 1, Pyruvate kinase-luciferase coupled assay", "abstract": + null, "venue": "", "year": 2010, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2010-08-06", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "3275486", "name": "M. Boxer"}, + {"authorId": "4084746", "name": "Jian-Kang Jiang"}, {"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "145829790", "name": "M. Shen"}, {"authorId": + "1799343", "name": "H. Veith"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2148769632", "name": "Craig J. Thomas"}]}, {"paperId": "91fde10af79259e572c71b10f4b3ea2de0012e38", + "externalIds": {"MAG": "2167699749", "DOI": "10.1158/1538-7445.AM10-LB-188", + "CorpusId": 74544484}, "corpusId": 74544484, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/91fde10af79259e572c71b10f4b3ea2de0012e38", + "title": "Abstract LB-188: Positive regulation of the Ras oncogene by ubiquitination", + "abstract": "Proceedings: AACR 101st Annual Meeting 2010\u2010\u2010 Apr 17\u201021, + 2010; Washington, DC\n\nDiscussion \n\nCitation Format: {Authors}. {Abstract + title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American + Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia + (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-188.", "venue": "", + "year": 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Physics", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2010-04-15", "journal": {"volume": "70", "name": "Cancer Research"}, "authors": + [{"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "9e88c75f809f013914433cc83f73cf44f3d8a3cb", "externalIds": + {"MAG": "2077223675", "DOI": "10.1016/j.gde.2009.11.002", "CorpusId": 205003010, + "PubMed": "20006486"}, "corpusId": 205003010, "publicationVenue": {"id": "c828ed19-475e-4afd-ab62-1eac0a2dae95", + "name": "Current Opinion in Genetics and Development", "type": "journal", + "alternate_names": ["Current Opinion in Genetics & Development", "Curr Opin + Genet Dev", "Curr Opin Genet Dev"], "issn": "0959-437X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/601302/description#description", + "alternate_urls": ["https://www.sciencedirect.com/journal/current-opinion-in-genetics-and-development", + "http://www.sciencedirect.com/science/journal/0959437X"]}, "url": "https://www.semanticscholar.org/paper/9e88c75f809f013914433cc83f73cf44f3d8a3cb", + "title": "Targeting the PI3K signaling pathway in cancer.", "abstract": null, + "venue": "Current Opinion in Genetics and Development", "year": 2010, "referenceCount": + 32, "citationCount": 543, "influentialCitationCount": 16, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2822054?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "2010-02-01", "journal": {"volume": "20 1", "pages": "\n 87-90\n ", + "name": "Current opinion in genetics & development"}, "authors": [{"authorId": + "32596484", "name": "Kwok-Kin Wong"}, {"authorId": "6828387", "name": "J. + Engelman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "a9b7191f238cd3c74ccff2b364869dfc2c56b33d", + "externalIds": {"PubMedCentral": "2965861", "MAG": "2052299248", "DOI": "10.1038/sj.bjc.6605846", + "CorpusId": 876260, "PubMed": "20808308"}, "corpusId": 876260, "publicationVenue": + {"id": "a7abfa95-0b9f-4416-9cd2-3271591663d2", "name": "British Journal of + Cancer", "type": "journal", "alternate_names": ["Br J Cancer"], "issn": "0007-0920", + "url": "http://www.bjcancer.com/", "alternate_urls": ["http://www.nature.com/bjc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/a9b7191f238cd3c74ccff2b364869dfc2c56b33d", + "title": "Prognostic significance of AMP-activated protein kinase expression + and modifying effect of MAPK3/1 in colorectal cancer", "abstract": null, "venue": + "British Journal of Cancer", "year": 2010, "referenceCount": 67, "citationCount": + 72, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.nature.com/articles/6605846.pdf", "status": null}, "fieldsOfStudy": + ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "external"}, {"category": "Medicine", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2010-08-31", "journal": + {"volume": "103", "pages": "1025 - 1033", "name": "British Journal of Cancer"}, + "authors": [{"authorId": "4428601", "name": "Y. Baba"}, {"authorId": "5913727", + "name": "K. Nosho"}, {"authorId": "1921948", "name": "K. Shima"}, {"authorId": + "1398014051", "name": "J. Meyerhardt"}, {"authorId": "2168928633", "name": + "A. Chan"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "6213932", "name": "M. Loda"}, {"authorId": + "144786791", "name": "E. Giovannucci"}, {"authorId": "1710084", "name": "C. + Fuchs"}, {"authorId": "3513211", "name": "S. Ogino"}]}, {"paperId": "ac219e4a263eac45831bbc0cb7d5eb0740f554be", + "externalIds": {"MAG": "2091903353", "DOI": "10.1016/j.molcel.2010.05.007", + "CorpusId": 23547764, "PubMed": "20513425"}, "corpusId": 23547764, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/ac219e4a263eac45831bbc0cb7d5eb0740f554be", + "title": "Glucose addiction of TSC null cells is caused by failed mTORC1-dependent + balancing of metabolic demand with supply.", "abstract": null, "venue": "Molecules + and Cells", "year": 2010, "referenceCount": 36, "citationCount": 256, "influentialCitationCount": + 11, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2010-05-28", "journal": {"volume": "38 4", "pages": "\n 487-99\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "32210637", "name": "A. + Y. Choo"}, {"authorId": "46876889", "name": "Sang Gyun Kim"}, {"authorId": + "3804233", "name": "M. V. Vander Heiden"}, {"authorId": "48247811", "name": + "S. J. Mahoney"}, {"authorId": "46470616", "name": "H. Vu"}, {"authorId": + "6168327", "name": "Sang-Oh Yoon"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4037343", "name": "J. Blenis"}]}, {"paperId": "bd359739df1868773ee3193ea970f1558f15bb7a", + "externalIds": {"CorpusId": 199399923}, "corpusId": 199399923, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/bd359739df1868773ee3193ea970f1558f15bb7a", + "title": "Identification of small molecule inhibitors of pyruvate kinase M + 2", "abstract": "A common feature of tumors arising from diverse tissue types + is a reliance on aerobic glycolysis for glucose metabolism. This metabolic + difference between cancer cells and normal cells could be exploited for therapeutic + benefit in patients. Cancer cells universally express the M2 isoform of the + glycolytic enzyme pyruvate kinase (PKM2), and previous work has demonstrated + that PKM2 expression is necessary for aerobic glycolysis and cell proliferation + in vivo. Because most normal tissues express an isoform of pyruvate kinase + other than PKM2, selective targeting of PKM2 provides an opportunity to target + cell metabolism for cancer therapy. PKM2 has an identical catalytic site as + the related M1 splice variant (PKM1). However, isoform selective inhibition + is possible as PKM2 contains a unique region for allosteric regulation. We + have screened a library of greater than 100,000 small molecules to identify + such inhibitors. The inhibitors identified for PKM2 fell primarily into three + distinct structural classes. The most potent PKM2 inhibitor resulted in decreased + glycolysis and increased cell death following loss of growth factor signaling. + At least part of this effect was due to on-target PKM2 inhibition as less + cell death was observed in cells engineered to express PKM1. These data suggest + that isoform selective inhibition of PKM2 with small molecules is feasible + and support the hypothesis that inhibition of glucose metabolism in cancer + cells is a viable strategy to treat human malignancy.", "venue": "", "year": + 2010, "referenceCount": 22, "citationCount": 22, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "4164415", "name": "H. Christofk"}, + {"authorId": "37745571", "name": "E. Schuman"}, {"authorId": "90190441", "name": + "O. Alexander"}, {"authorId": "2105377681", "name": "Subtelny"}, {"authorId": + "4536882", "name": "H. Sharfi"}, {"authorId": "143686358", "name": "E. Harlow"}, + {"authorId": "13566176", "name": "Jun Xian"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "d5b1fb5b851050629034b90521a7346bd6acc610", "externalIds": + {"MAG": "1985599023", "DOI": "10.1016/j.cmet.2010.11.005", "CorpusId": 27643634, + "PubMed": "21109194"}, "corpusId": 27643634, "publicationVenue": {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", + "name": "Cell Metabolism", "type": "journal", "alternate_names": ["Cell Metab"], + "issn": "1550-4131", "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/15504131", "http://www.cellmetabolism.org/"]}, + "url": "https://www.semanticscholar.org/paper/d5b1fb5b851050629034b90521a7346bd6acc610", + "title": "Class IA phosphatidylinositol 3-kinase in pancreatic \u03b2 cells + controls insulin secretion by multiple mechanisms.", "abstract": null, "venue": + "Cell Metabolism", "year": 2010, "referenceCount": 62, "citationCount": 96, + "influentialCitationCount": 7, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.cell.com/article/S1550413110003979/pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2010-12-01", "journal": + {"volume": "12 6", "pages": "\n 619-32\n ", "name": "Cell + metabolism"}, "authors": [{"authorId": "2061403809", "name": "Kazuma Kaneko"}, + {"authorId": "5177377", "name": "K. Ueki"}, {"authorId": "47893508", "name": + "N. Takahashi"}, {"authorId": "123302527", "name": "Shinji Hashimoto"}, {"authorId": + "123075443", "name": "M. Okamoto"}, {"authorId": "4292978", "name": "M. Awazawa"}, + {"authorId": "40289171", "name": "Yukiko Okazaki"}, {"authorId": "35179845", + "name": "M. Ohsugi"}, {"authorId": "6805315", "name": "K. Inabe"}, {"authorId": + "37289333", "name": "T. Umehara"}, {"authorId": "145329883", "name": "Masashi + Yoshida"}, {"authorId": "4801935", "name": "M. Kakei"}, {"authorId": "32660808", + "name": "T. Kitamura"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "144242661", "name": "R. Kulkarni"}, {"authorId": "144391716", "name": "C. + Kahn"}, {"authorId": "32414353", "name": "H. Kasai"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "34587810", "name": "T. Kadowaki"}]}, + {"paperId": "e3bea883d3a051fbde6a4c2f3b430622036ed965", "externalIds": {"CorpusId": + 35625091}, "corpusId": 35625091, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e3bea883d3a051fbde6a4c2f3b430622036ed965", + "title": "Cancer evention esearch pective rspective on Memmott et al . , p + . 1066 Pr R moprevention Meets Glucose Control", "abstract": "Downlo report + by Memmott et al. (beginning on page 1066 in this issue of the journal) assessing + the efficacy antidiabetes drug metformin in a mouse model of lung carcinogenesis + suggests protective effects via ossible avenues: Decreased circulating insulin + and insulin-like growth factor levels and energy stress g to inhibition of + mammalian target of rapamycin signaling. These potential mechanisms are disleadin + cussed in this perspective, as are their implications for cancer prevention + and therapy. Cancer Prev Res; 3(9); 1049\u201352. \u00a92010 AACR.", "venue": + "", "year": 2010, "referenceCount": 25, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Medicine", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "103572289", "name": "Y. Engelman"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "e8c7c243658808e72432469b164067d5855fd123", + "externalIds": {"MAG": "2556333180", "DOI": "10.1182/BLOOD.V116.21.3142.3142", + "CorpusId": 89600254}, "corpusId": 89600254, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/e8c7c243658808e72432469b164067d5855fd123", + "title": "Leukemogenic Tyrosine Kinases Inhibit PKM2 to Promote the Warburg + Effect and Tumor Growth", "abstract": "Abstract 3142 The Warburg effect describes + a pro-oncogenic metabolic switch in which cancer cells, including leukemia + cells, take up more glucose than normal tissue, yet use less glucose for oxidative + phosphorylation and favor glycolysis even in the presence of oxygen (aerobic + glycolysis). However, the molecular mechanisms underlying the Warburg effect + remain unclear. Growth factor (GF) receptors are believed to play a key role + in programming cancer cell metabolism. These GF receptors are expressed in + many hematopoietic malignancies as constitutively activated tyrosine kinase + mutants. Thus, we examinined whether tyrosine kinase signaling \u2014 commonly + upregulated in hematopoietic malignancies \u2014 regulates the Warburg effect + to contribute to leukemogenesis and disease progression. We performed phospho-proteomics + studies and found that pyruvate kinase M2 isoform (PKM2), which is a rate-limiting + enzyme of glycolysis, is tyrosine phosphorylated in leukemia cells expressing + FGFR1 fusion tyrosine kinases, which are associated with 8p11 leukemia/lymphoma + syndrome. We also found that 8p11 leukemogenic FGFR1 directly phosphorylates + and inhibits PKM2. Recent seminal studies from Dr. Lew Cantley9s group demonstrated + that the enzymatic activity of PKM2 is inhibited by phosphotyrosine binding; + PKM2 expression is important for aerobic glycolysis and provides a growth + advantage to tumors. However, it remains unclear which dedicated tyrosine + kinase pathways are physiologically responsible for this regulation and whether + PKM2 itself is tyrosine phosphorylated to achieve inhibition of PKM2 in cancer + cells. Here we report that FGFR1 inhibits PKM2 by direct phosphorylation at + Y105. This consequently inhibits the formation of tetrameric, active PKM2 + by disrupting cofactor fructose-1,6-bisphosphate (FBP) binding in a putative + \u201cinter-molecule manner\u201d, where one molecule in an active PKM2 tetramer, + when phosphorylated, may function as an inhibitory binding partner to the + other sister molecules. In addition, phosphorylation of PKM2 at Y105 is common + in many human leukemia cell lines expressing oncogenic tyrosine kinases such + as BCR-ABL, FLT3-ITD, and JAK2V617F. Furthermore, expression of the PKM2 Y105F + mutant in cancer cells following RNAi-mediated knockdown of endogenous PKM2 + leads to decreased cell proliferation under hypoxia, increased oxidative phosphorylation + with reduced lactate production, and reduced tumor growth in xenograft nude + mice. Our findings suggest that tyrosine phosphorylation regulates PKM2 to + program cancer cell metabolism and promote tumor growth. This may represent + a common, acute molecular mechanism to regulate the Warburg effect, in addition + to the chronic changes that are believed to be regulated by hypoxia inducible + factor 1 and Myc. Disclosures: No relevant conflicts of interest to declare.", + "venue": "", "year": 2010, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "2010-11-19", + "journal": {"volume": "116", "pages": "3142-3142", "name": "Blood"}, "authors": + [{"authorId": "5648825", "name": "T. Hitosugi"}, {"authorId": "6357969", "name": + "Sumin Kang"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "3712752", "name": "T. Chung"}, {"authorId": "46955429", "name": "Shannon + E Elf"}, {"authorId": "13728283", "name": "Katherine Lythgoe"}, {"authorId": + "6137304", "name": "S. Dong"}, {"authorId": "4891579", "name": "S. Lonial"}, + {"authorId": "2108598823", "name": "Xu Wang"}, {"authorId": "32401310", "name": + "G. Chen"}, {"authorId": "143740055", "name": "Jianxin Xie"}, {"authorId": + "40075084", "name": "T. Gu"}, {"authorId": "4032764", "name": "R. Polakiewicz"}, + {"authorId": "6151924", "name": "J. Roesel"}, {"authorId": "3907849", "name": + "T. Boggon"}, {"authorId": "5531063", "name": "F. Khuri"}, {"authorId": "2246160", + "name": "D. Gilliland"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5224106", "name": "J. Kaufman"}, {"authorId": "5152140", "name": "J. Chen"}]}, + {"paperId": "ea552254f1f0d220bc05c7f2f8296486345607ea", "externalIds": {"PubMedCentral": + "2866327", "MAG": "1983839663", "DOI": "10.1371/journal.pone.0010504", "CorpusId": + 3872863, "PubMed": "20498699"}, "corpusId": 3872863, "publicationVenue": {"id": + "0aed7a40-85f3-4c66-9e1b-c1556c57001b", "name": "PLoS ONE", "type": "journal", + "alternate_names": ["Plo ONE", "PLOS ONE", "PLO ONE"], "issn": "1932-6203", + "url": "https://journals.plos.org/plosone/", "alternate_urls": ["http://www.plosone.org/"]}, + "url": "https://www.semanticscholar.org/paper/ea552254f1f0d220bc05c7f2f8296486345607ea", + "title": "Designed Inhibitors of Insulin-Degrading Enzyme Regulate the Catabolism + and Activity of Insulin", "abstract": "Background Insulin is a vital peptide + hormone that is a central regulator of glucose homeostasis, and impairments + in insulin signaling cause diabetes mellitus. In principle, it should be possible + to enhance the activity of insulin by inhibiting its catabolism, which is + mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily + distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition + of IDE as an attractive anti-diabetic approach dating to the 1950s, potent + and selective inhibitors of IDE have not yet emerged. Methodology/Principal + Findings We used a rational design approach based on analysis of combinatorial + peptide mixtures and focused compound libraries to develop novel peptide hydroxamic + acid inhibitors of IDE. The resulting compounds are \u223c106 times more potent + than existing inhibitors, non-toxic, and surprisingly selective for IDE vis-\u00e0-vis + conventional zinc-metalloproteases. Crystallographic analysis of an IDE-inhibitor + complex reveals a novel mode of inhibition based on stabilization of IDE''s + \u201cclosed,\u201d inactive conformation. We show further that pharmacological + inhibition of IDE potentiates insulin signaling by a mechanism involving reduced + catabolism of internalized insulin. Conclusions/Significance The inhibitors + we describe are the first to potently and selectively inhibit IDE or indeed + any member of this atypical zinc-metalloprotease superfamily. The distinctive + structure of IDE''s active site, and the mode of action of our inhibitors, + suggests that it may be possible to develop inhibitors that cross-react minimally + with conventional zinc-metalloproteases. Significantly, our results reveal + that insulin signaling is normally regulated by IDE activity not only extracellularly + but also within cells, supporting the longstanding view that IDE inhibitors + could hold therapeutic value for the treatment of diabetes.", "venue": "PLoS + ONE", "year": 2010, "referenceCount": 56, "citationCount": 96, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010504&type=printable", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2010-05-07", "journal": {"volume": "5", "name": "PLoS + ONE"}, "authors": [{"authorId": "6667807", "name": "M. Leissring"}, {"authorId": + "46377688", "name": "E. Malito"}, {"authorId": "6044838", "name": "Sabrine + H\u00e9douin"}, {"authorId": "4111437", "name": "L. Reinstatler"}, {"authorId": + "48713460", "name": "Tomoko Sahara"}, {"authorId": "1395003715", "name": "S. + Abdul-Hay"}, {"authorId": "35359166", "name": "Shakeel Choudhry"}, {"authorId": + "92904229", "name": "Ghulam M. Maharvi"}, {"authorId": "4218139", "name": + "A. Fauq"}, {"authorId": "49088275", "name": "M. Huzarska"}, {"authorId": + "2070635457", "name": "Philip S. May"}, {"authorId": "98570863", "name": "Sungwoong + Choi"}, {"authorId": "36589908", "name": "Todd Logan"}, {"authorId": "25581223", + "name": "B. Turk"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "34905390", "name": "M. Manolopoulou"}, {"authorId": "1766067", "name": "Wei-Jen + Tang"}, {"authorId": "113262814", "name": "R. Stein"}, {"authorId": "35117700", + "name": "G. Cuny"}, {"authorId": "4190578", "name": "D. Selkoe"}]}, {"paperId": + "f51f52bc076e2d0080c598fc90f2a2290c9066c2", "externalIds": {"MAG": "2013276658", + "DOI": "10.1016/S1359-6349(10)71865-6", "CorpusId": 71188166}, "corpusId": + 71188166, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/f51f52bc076e2d0080c598fc90f2a2290c9066c2", + "title": "160 Cancer-associated IDH1 and IDH2 mutations: therapeutic opportunities", + "abstract": null, "venue": "", "year": 2010, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2010-11-01", "journal": {"volume": + "8", "pages": "56", "name": "Ejc Supplements"}, "authors": [{"authorId": "5210229", + "name": "Shengfang Jin"}, {"authorId": "38799894", "name": "L. Dang"}, {"authorId": + "144707828", "name": "S. Gross"}, {"authorId": "4691854", "name": "E. Driggers"}, + {"authorId": "4886372", "name": "K. Yen"}, {"authorId": "3564730", "name": + "M. Bittinger"}, {"authorId": "31604076", "name": "C. Thompson"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "39135065", "name": "Michael + Su"}, {"authorId": "4936699", "name": "V. Fantin"}]}, {"paperId": "0d8f82ac6ac15f16debac0a968e66e9455942a94", + "externalIds": {"MAG": "2097259163", "DOI": "10.1126/science.1160809", "CorpusId": + 4598043, "PubMed": "19460998"}, "corpusId": 4598043, "publicationVenue": {"id": + "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": "journal", + "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/0d8f82ac6ac15f16debac0a968e66e9455942a94", + "title": "Understanding the Warburg Effect: The Metabolic Requirements of + Cell Proliferation", "abstract": "Fuel Economy for Growing Cells Sophisticated + 21st-century analyses of the signaling pathways that control cell growth have + led researchers back to the seminal work of Otto Warburg, who discovered in + the 1920s that tumor cells generate their energy in an unusual way\u2014by + switching from mitochondrial respiration to glycolysis. The advantage conferred + by this metabolic switch is puzzling because mitochondrial respiration is + a more efficient way to produce ATP. Vander Heiden et al. (p. 1029) review + arguments that rapidly growing cells have critical metabolic requirements + that extend beyond ATP and that a better understanding of these requirements + may shed new light on the \u201cWarburg effect\u201d and ultimately lead to + new therapies for cancer. In contrast to normal differentiated cells, which + rely primarily on mitochondrial oxidative phosphorylation to generate the + energy needed for cellular processes, most cancer cells instead rely on aerobic + glycolysis, a phenomenon termed \u201cthe Warburg effect.\u201d Aerobic glycolysis + is an inefficient way to generate adenosine 5\u2032-triphosphate (ATP), however, + and the advantage it confers to cancer cells has been unclear. Here we propose + that the metabolism of cancer cells, and indeed all proliferating cells, is + adapted to facilitate the uptake and incorporation of nutrients into the biomass + (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. + Supporting this idea are recent studies showing that (i) several signaling + pathways implicated in cell proliferation also regulate metabolic pathways + that incorporate nutrients into biomass; and that (ii) certain cancer-associated + mutations enable cancer cells to acquire and metabolize nutrients in a manner + conducive to proliferation rather than efficient ATP production. A better + understanding of the mechanistic links between cellular metabolism and growth + control may ultimately lead to better treatments for human cancer.", "venue": + "Science", "year": 2009, "referenceCount": 65, "citationCount": 11852, "influentialCitationCount": + 458, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2849637?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2009-05-22", "journal": + {"volume": "324", "pages": "1029 - 1033", "name": "Science"}, "authors": [{"authorId": + "3804233", "name": "M. V. Vander Heiden"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "31604076", "name": "C. Thompson"}]}, {"paperId": + "1104cfc1f233d9208b1b1177499b56cb8996e982", "externalIds": {"CorpusId": 17179248}, + "corpusId": 17179248, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/1104cfc1f233d9208b1b1177499b56cb8996e982", + "title": "Stefan Wuchty , of Knowledge The Increasing Dominance of Teams in + Production", "abstract": "http://www.sciencemag.org/cgi/content/full/316/5827/1036 + version of this article at: including high-resolution figures, can be found + in the online Updated information and services, http://www.sciencemag.org/cgi/content/full/1136099/DC1 + can be found at: Supporting Online Material found at: can be related to this + article A list of selected additional articles on the Science Web sites http://www.sciencemag.org/cgi/content/full/316/5827/1036#related-content + http://www.sciencemag.org/cgi/content/full/316/5827/1036#otherarticles , 3 + of which can be accessed for free: cites 14 articles This article 45 article(s) + on the ISI Web of Science. cited by This article has been http://www.sciencemag.org/cgi/content/full/316/5827/1036#otherarticles + 10 articles hosted by HighWire Press; see: cited by This article has been + http://www.sciencemag.org/cgi/collection/sociology Sociology : subject collections + This article appears in the following", "venue": "", "year": 2009, "referenceCount": + 36, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Business", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": null, "authors": [{"authorId": "5610750", "name": "K. Zejnullahu"}, + {"authorId": "4441512", "name": "T. Mitsudomi"}, {"authorId": "121610638", + "name": "Youngchul Song"}, {"authorId": "40053421", "name": "Courtney Hyland"}, + {"authorId": "48490520", "name": "Joon-Oh Park"}, {"authorId": "3734755", + "name": "N. Lindeman"}, {"authorId": "77094637", "name": "Christopher-Michael + Gale"}, {"authorId": "2111027786", "name": "Xiaojun Zhao"}, {"authorId": "2054179920", + "name": "J. Christensen"}, {"authorId": "2638484", "name": "T. Kosaka"}, {"authorId": + "48115918", "name": "A. Holmes"}, {"authorId": "2056849769", "name": "A. M. + Rogers"}, {"authorId": "3740336", "name": "F. Cappuzzo"}, {"authorId": "17750315", + "name": "T. Mok"}, {"authorId": "2118593740", "name": "Charles Lee"}, {"authorId": + "2111408112", "name": "Bruce E. Johnson"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "12567efdc6f85b862b3523fc9ece405950cc3b3c", "externalIds": + {"MAG": "2100260504", "DOI": "10.1126/scisignal.2000431", "CorpusId": 7194806, + "PubMed": "19920251"}, "corpusId": 7194806, "publicationVenue": {"id": "c0efe552-8a0a-41a7-8ce2-340fb0dbfe6f", + "name": "Science Signaling", "type": "journal", "alternate_names": ["Sci Signal"], + "issn": "1945-0877", "url": "https://www.sciencemag.org/", "alternate_urls": + ["https://stke.sciencemag.org/about/", "https://stke.sciencemag.org/"]}, "url": + "https://www.semanticscholar.org/paper/12567efdc6f85b862b3523fc9ece405950cc3b3c", + "title": "Tyrosine Phosphorylation Inhibits PKM2 to Promote the Warburg Effect + and Tumor Growth", "abstract": "Tyrosine phosphorylation of pyruvate kinase + M2 gives tumor cells a metabolic advantage. A Malignant Metabolic Switch Cancer + cells show aberrant metabolism, consuming more glucose than do healthy cells + and producing lactate even in the presence of abundant oxygen, rather than + shifting to oxidative phosphorylation. This phenomenon is called the Warburg + effect, after Otto Warburg, who described it many years ago. Building on recent + research implicating inhibition of the M2 isoform of the glycolytic enzyme + pyruvate kinase (PKM2) by phosphotyrosine binding as critical to the Warburg + effect\u2014and tumorigenesis\u2014Hitosugi et al. explored the role of signaling + from oncogenic forms of the fibroblast growth factor receptor type 1 (FGFR1) + in mediating this metabolic switch. They found that FGFR1, a receptor tyrosine + kinase, phosphorylated a tyrosine residue (Y105) on PKM2 itself. Further analysis + revealed that this tyrosine residue was commonly phosphorylated in human cancers + and that a mutant form of PKM2 lacking this tyrosine residue inhibited both + \u201cWarburg metabolism\u201d and tumor growth. They thus propose that phosphorylation + of PKM2 by oncogenic tyrosine kinases provides the very phosphotyrosine that + binds to and inhibits PKM2 to induce the Warburg effect and promote tumor + growth. The Warburg effect describes a pro-oncogenic metabolism switch such + that cancer cells take up more glucose than normal tissue and favor incomplete + oxidation of glucose even in the presence of oxygen. To better understand + how tyrosine kinase signaling, which is commonly increased in tumors, regulates + the Warburg effect, we performed phosphoproteomic studies. We found that oncogenic + forms of fibroblast growth factor receptor type 1 inhibit the pyruvate kinase + M2 (PKM2) isoform by direct phosphorylation of PKM2 tyrosine residue 105 (Y105). + This inhibits the formation of active, tetrameric PKM2 by disrupting binding + of the PKM2 cofactor fructose-1,6-bisphosphate. Furthermore, we found that + phosphorylation of PKM2 Y105 is common in human cancers. The presence of a + PKM2 mutant in which phenylalanine is substituted for Y105 (Y105F) in cancer + cells leads to decreased cell proliferation under hypoxic conditions, increased + oxidative phosphorylation with reduced lactate production, and reduced tumor + growth in xenografts in nude mice. Our findings suggest that tyrosine phosphorylation + regulates PKM2 to provide a metabolic advantage to tumor cells, thereby promoting + tumor growth.", "venue": "Science Signaling", "year": 2009, "referenceCount": + 35, "citationCount": 671, "influentialCitationCount": 50, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2812789?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-11-17", "journal": {"volume": "2", "pages": "ra73 + - ra73", "name": "Science Signaling"}, "authors": [{"authorId": "5648825", + "name": "T. Hitosugi"}, {"authorId": "6357969", "name": "Sumin Kang"}, {"authorId": + "3804233", "name": "M. V. Vander Heiden"}, {"authorId": "2151016785", "name": + "Tae-Wook Chung"}, {"authorId": "46955429", "name": "Shannon E Elf"}, {"authorId": + "13728283", "name": "Katherine Lythgoe"}, {"authorId": "6137304", "name": + "S. Dong"}, {"authorId": "4891579", "name": "S. Lonial"}, {"authorId": "2108598823", + "name": "Xu Wang"}, {"authorId": "32401310", "name": "G. Chen"}, {"authorId": + "143740055", "name": "Jianxin Xie"}, {"authorId": "40075084", "name": "T. + Gu"}, {"authorId": "4032764", "name": "R. Polakiewicz"}, {"authorId": "6151924", + "name": "J. Roesel"}, {"authorId": "3907849", "name": "T. Boggon"}, {"authorId": + "5531063", "name": "F. Khuri"}, {"authorId": "2246160", "name": "D. Gilliland"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5224106", "name": + "J. Kaufman"}, {"authorId": "40337424", "name": "Jing Chen"}]}, {"paperId": + "141c09067d0d54897476a5a8dc0b2365ca4d4c4b", "externalIds": {"MAG": "2108746644", + "DOI": "10.1158/1535-7163.MCT-08-1012", "CorpusId": 6528350, "PubMed": "19509266"}, + "corpusId": 6528350, "publicationVenue": {"id": "05590b5e-de5a-404d-bec3-bfe1e9d96382", + "name": "Molecular Cancer Therapeutics", "type": "journal", "alternate_names": + ["Mol Cancer Ther"], "issn": "1535-7163", "url": "https://mct.aacrjournals.org/"}, + "url": "https://www.semanticscholar.org/paper/141c09067d0d54897476a5a8dc0b2365ca4d4c4b", + "title": "The antiproliferative cytostatic effects of a self-activating viridin + prodrug", "abstract": "Although viridins like wortmannin (Wm) have long been + examined as anticancer agents, their ability to self-activate has only recently + been recognized. Here, we describe the cytostatic effects of a self-activating + viridin (SAV), which is an inactive, polymeric prodrug. SAV self-activates + to generate a bioactive, fluorescent viridin NBD-Wm with a half-time of 9.2 + hours. With cultured A549 cells, 10 \u03bcmol/L SAV caused growth arrest without + inducing apoptosis or cell death, a cytostatic action markedly different from + other chemotherapeutic agents (vinblastine, camptothecin, and paclitaxel). + In vivo, a SAV dosing of 1 mg/kg once in 48 hours (i.p.) resulted in growth + arrest of an A549 tumor xenograft, with growth resuming when dosing ceased. + With a peak serum concentration of SAV of 2.36 \u03bcmol/L (at 2 hours post + i.p. injection), the concentration of bioactive NBD-Wm was 41 nmol/L based + on the partial inhibition of neutrophil respiratory burst. Therefore, SAV + was present as an inactive prodrug in serum (peak = 2.36 \u03bcmol/L), which + generated low concentrations of active viridin (41 nmol/L). SAV is a prodrug, + the slow release and cytostatic activities of which suggest that it might + be useful as a component of metronomic-based chemotherapeutic strategies. + [Mol Cancer Ther 2009;8(6):1666\u201375]", "venue": "Molecular Cancer Therapeutics", + "year": 2009, "referenceCount": 31, "citationCount": 16, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://aacrjournals.org/mct/article-pdf/8/6/1666/1884036/1666.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}, {"category": "Medicine", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2009-06-01", "journal": {"volume": "8", "pages": "1666 - 1675", "name": "Molecular + Cancer Therapeutics"}, "authors": [{"authorId": "2109352731", "name": "Adam + Smith"}, {"authorId": "37048404", "name": "Joseph T. Blois"}, {"authorId": + "6230104", "name": "Hushan Yuan"}, {"authorId": "3280645", "name": "E. Aikawa"}, + {"authorId": "3579696", "name": "C. Ellson"}, {"authorId": "46728536", "name": + "Jose-Luiz Figueiredo"}, {"authorId": "3127756", "name": "R. Weissleder"}, + {"authorId": "3517894", "name": "Rainer H. Kohler"}, {"authorId": "88402408", + "name": "M. Yaffe"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5095505", "name": "L. Josephson"}]}, {"paperId": "2b793875fa5210f8c09f434be555e9c0350e600a", + "externalIds": {"MAG": "2103414735", "DOI": "10.1200/JCO.2008.18.6544", "CorpusId": + 37687233, "PubMed": "19237633"}, "corpusId": 37687233, "publicationVenue": + {"id": "a5913268-3957-484f-b41f-347b0ba23338", "name": "Journal of Clinical + Oncology", "type": "journal", "alternate_names": ["J Clin Oncol"], "issn": + "0732-183X", "url": "https://ascopubs.org/loi/jco", "alternate_urls": ["http://www.jco.org/", + "http://jco.ascopubs.org/"]}, "url": "https://www.semanticscholar.org/paper/2b793875fa5210f8c09f434be555e9c0350e600a", + "title": "PIK3CA mutation is associated with poor prognosis among patients + with curatively resected colon cancer.", "abstract": "PURPOSE\nPIK3CA mutation + and subsequent activation of the AKT pathway play an important role in colorectal + carcinogenesis. However, little is known about the prognostic role of PIK3CA + mutation in colon cancer.\n\n\nPATIENTS AND METHODS\nUsing 450 resectable + colon cancers (stage I to III) in two independent prospective cohorts, we + detected PIK3CA mutation in 82 tumors (18%) by pyrosequencing. Cox proportional + hazards models were used to calculate hazard ratios (HRs) of colon cancer-specific + and overall mortalities, adjusted for patient characteristics and tumoral + molecular features, including the CpG island methylation phenotype, microsatellite + instability (MSI), LINE-1 hypomethylation, and p53, CIMP, KRAS and BRAF mutation.\n\n\nRESULTS\nCompared + with patients with PIK3CA wild-type tumors, those with PIK3CA-mutated tumors + experienced an increase in colon cancer-specific mortality according to univariate + analysis (HR = 1.64; 95% CI, 0.95 to 2.86), which persisted after adjusting + for other known or potential risk factors for cancer recurrence (including + MSI; multivariate HR = 2.23; 95% CI, 1.21 to 4.11). The effect of PIK3CA mutation + on cancer survival seemed to differ according to KRAS mutational status. Among + patients with KRAS wild-type tumors, the presence of PIK3CA mutation was associated + with a significant increase in colon cancer-specific mortality (HR = 3.80; + 95% CI, 1.56 to 9.27). In contrast, PIK3CA mutation conferred no significant + effect on mortality among patients with KRAS-mutated tumors (HR = 1.25; 95% + CI, 0.52 to 2.96).\n\n\nCONCLUSION\nAmong patients who undergo a curative + resection of colon cancer, PIK3CA mutation is associated with shorter cancer-specific + survival. The adverse effect of PIK3CA mutation may be potentially limited + to patients with KRAS wild-type tumors.", "venue": "Journal of Clinical Oncology", + "year": 2009, "referenceCount": 45, "citationCount": 322, "influentialCitationCount": + 21, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2009-03-20", "journal": + {"volume": "27 9", "pages": "\n 1477-84\n ", "name": "Journal + of clinical oncology : official journal of the American Society of Clinical + Oncology"}, "authors": [{"authorId": "3513211", "name": "S. Ogino"}, {"authorId": + "5913727", "name": "K. Nosho"}, {"authorId": "5726687", "name": "G. Kirkner"}, + {"authorId": "1921948", "name": "K. Shima"}, {"authorId": "5888152", "name": + "N. Irahara"}, {"authorId": "21523224", "name": "Shoko Kure"}, {"authorId": + "2168928633", "name": "A. Chan"}, {"authorId": "6828387", "name": "J. Engelman"}, + {"authorId": "143832374", "name": "P. Kraft"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "144786791", "name": "E. Giovannucci"}, {"authorId": + "1710084", "name": "C. Fuchs"}]}, {"paperId": "32b1eaf84a1a3784fcddce31326be24410915f91", + "externalIds": {"MAG": "2154350109", "DOI": "10.1158/1078-0432.CCR-09-2305", + "CorpusId": 14250276, "PubMed": "19903790"}, "corpusId": 14250276, "publicationVenue": + {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", "name": "Clinical Cancer Research", + "type": "journal", "alternate_names": ["Clin Cancer Res"], "issn": "1078-0432", + "url": "https://clincancerres.aacrjournals.org/", "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, + "url": "https://www.semanticscholar.org/paper/32b1eaf84a1a3784fcddce31326be24410915f91", + "title": "Getting Knit-PI3Ky: PIK3CA Mutation Status to Direct Multimodality + Therapy?", "abstract": "There is high morbidity associated with local recurrence + of rectal cancer. However, the adjuvant therapies given to prevent such recurrences + also have significant side effects and associated risks. The ability to select + patients with the highest risk of recurrence and greatest therapeutic response + will improve rectal cancer care. (Clin Cancer Res 2009;15(22):674850)", "venue": + "Clinical Cancer Research", "year": 2009, "referenceCount": 13, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc3400141?pdf=render", "status": null}, "fieldsOfStudy": + ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-11-10", "journal": {"volume": "15", "pages": "6748 + - 6750", "name": "Clinical Cancer Research"}, "authors": [{"authorId": "6324437", + "name": "A. Myers"}, {"authorId": "3859322", "name": "J. Meyerhardt"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "4b03f59f6b553a36324d4849dacb00deb2900f6d", + "externalIds": {"MAG": "2753561643", "DOI": "10.1073/PNAS.0905401106", "CorpusId": + 59191106}, "corpusId": 59191106, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4b03f59f6b553a36324d4849dacb00deb2900f6d", + "title": "Sj\u00f6gren''s syndrome-like disease in mice with T cells lacking + class 1A phosphoinositide-3-kinase (Proceedings of the National Academy of + Sciences of the United States of America (2009) 103, 45, (16882-16887) 10.1073/pnas. + 0607984103)", "abstract": null, "venue": "", "year": 2009, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.pnas.org/content/106/26/10871.2.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2009-06-30", "journal": {"volume": + "106", "name": "Proceedings of the National Academy of Sciences of the United + States of America"}, "authors": [{"authorId": "39001132", "name": "J. Oak"}, + {"authorId": "33653557", "name": "Jonathan A. Deane"}, {"authorId": "152500082", + "name": "M. Kharas"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "2385578", "name": "T. Lane"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "6241317", "name": "D. Fruman"}]}, {"paperId": "593a97c57c763a51d1dd1ba8b6eb3109637ef860", + "externalIds": {"MAG": "2415206665", "DOI": "10.1016/j.cub.2009.06.010", "CorpusId": + 19060385, "PubMed": "19655422"}, "corpusId": 19060385, "publicationVenue": + {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", "name": "Current Biology", + "type": "journal", "alternate_names": ["Curr Biology"], "issn": "0960-9822", + "url": "http://www.current-biology.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/09609822"]}, + "url": "https://www.semanticscholar.org/paper/593a97c57c763a51d1dd1ba8b6eb3109637ef860", + "title": "Lewis C. Cantley", "abstract": null, "venue": "Current Biology", + "year": 2009, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0960982209012469/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Environmental Science", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2009-07-28", "journal": {"volume": + "19", "pages": "R540-R541", "name": "Current Biology"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "7ecfc763ee0c96cd424e39a088b6e31325ae7141", + "externalIds": {"MAG": "2080679736", "DOI": "10.1042/BJ20091035", "CorpusId": + 24699068, "PubMed": "19740074"}, "corpusId": 24699068, "publicationVenue": + {"id": "64838252-a209-4424-a778-3b86b4a83c48", "name": "Biochemical Journal", + "type": "journal", "alternate_names": ["Biochem J"], "issn": "0264-6021", + "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, "url": + "https://www.semanticscholar.org/paper/7ecfc763ee0c96cd424e39a088b6e31325ae7141", + "title": "Substrate specificity and inhibitors of LRRK2, a protein kinase + mutated in Parkinson''s disease.", "abstract": "The LRRK2 (leucine-rich repeat + protein kinase-2) is mutated in a significant number of Parkinson''s disease + patients, but little is known about its regulation and function. A common + mutation changing Gly2019 to serine enhances catalytic activity, suggesting + that small-molecule inhibitors might have utility in treating Parkinson''s + disease. We employed various approaches to explore the substrate-specificity + requirements of LRRK2 and elaborated a peptide substrate termed Nictide, that + had 20-fold lower Km and nearly 2-fold higher Vmax than the widely deployed + LRRKtide substrate. We demonstrate that LRRK2 has marked preference for phosphorylating + threonine over serine. We also observed that several ROCK (Rho kinase) inhibitors + such as Y-27632 and H-1152, suppressed LRRK2 with similar potency to which + they inhibited ROCK2. In contrast, GSK429286A, a selective ROCK inhibitor, + did not significantly inhibit LRRK2. We also identified a mutant LRRK2[A2016T] + that was normally active, but resistant to H-1152 and Y-27632, as well as + sunitinib, a structurally unrelated multikinase inhibitor that, in contrast + with other compounds, suppresses LRRK2, but not ROCK. We have also developed + the first sensitive antibody that enables measurement of endogenous LRRK2 + protein levels and kinase activity as well as shRNA (short hairpin RNA) methods + to reduce LRRK2 expression. Finally, we describe a pharmacological approach + to validate whether substrates are phosphorylated by LRRK2 and use this to + provide evidence that LRRK2 may not be rate-limiting for the phosphorylation + of the proposed substrate moesin. The findings of the present study will aid + with the investigation of LRRK2.", "venue": "Biochemical Journal", "year": + 2009, "referenceCount": 43, "citationCount": 197, "influentialCitationCount": + 19, "isOpenAccess": true, "openAccessPdf": {"url": "https://hal.archives-ouvertes.fr/hal-00479223/file/PEER_stage2_10.1042%252FBJ20091035.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2009-11-15", "journal": {"volume": + "424 1", "pages": "\n 47-60\n ", "name": "The Biochemical + journal"}, "authors": [{"authorId": "36960808", "name": "R. Nichols"}, {"authorId": + "46728221", "name": "N. Dzamko"}, {"authorId": "6742227", "name": "Jessica + E. Hutti"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4206645", + "name": "M. De\u00e1k"}, {"authorId": "46717397", "name": "Jennifer M. Moran"}, + {"authorId": "8064952", "name": "P. Bamborough"}, {"authorId": "46487022", + "name": "A. Reith"}, {"authorId": "3475566", "name": "D. Alessi"}]}, {"paperId": + "94e5fd34373defb83b52bd8f5b47a59780d73504", "externalIds": {"MAG": "1977952379", + "DOI": "10.1021/bc900176a", "CorpusId": 23079243, "PubMed": "19883074"}, "corpusId": + 23079243, "publicationVenue": {"id": "727c9075-57df-4276-83b3-a90e2722f883", + "name": "Bioconjugate chemistry", "type": "journal", "alternate_names": ["Bioconjugate + Chem", "Bioconjugate chem", "Bioconjugate Chemistry"], "issn": "1043-1802", + "url": "https://pubs.acs.org/journal/bcches", "alternate_urls": ["http://pubs.acs.org/journals/bcches/index.html", + "http://pubs.acs.org/journal/bcches"]}, "url": "https://www.semanticscholar.org/paper/94e5fd34373defb83b52bd8f5b47a59780d73504", + "title": "A wortmannin-cetuximab as a double drug.", "abstract": "Double drugs + are obtained when two pharmacologically active entities are covalently joined + to improve potency. We conjugated the viridin Wm with a self-activating linkage + to cetuximab and demonstrated the retention of immunoreactivity by the conjugate. + Though cetuximab lacked a growth inhibitory activity against A549 cells, the + Wm-cetuximab conjugate had an antiproliferative IC(50) of 155 nM in vitro. + The chemistry of attaching a self-releasing Wm to clinically approved antibodies + is general and, in selected instances, may yield antibody-based double drugs + with improved efficacy.", "venue": "Bioconjugate chemistry", "year": 2009, + "referenceCount": 28, "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3386608?pdf=render", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-11-02", "journal": {"volume": "20 11", "pages": "\n 2185-9\n ", + "name": "Bioconjugate chemistry"}, "authors": [{"authorId": "49310988", "name": + "R. Smith"}, {"authorId": "6230104", "name": "Hushan Yuan"}, {"authorId": + "3127756", "name": "R. Weissleder"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5095505", "name": "L. Josephson"}]}, {"paperId": "9fc366d0304be3fa2236f8fb210f5ea8f809160a", + "externalIds": {"MAG": "2062388859", "DOI": "10.1016/J.BONE.2009.01.127", + "CorpusId": 85157501}, "corpusId": 85157501, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/9fc366d0304be3fa2236f8fb210f5ea8f809160a", + "title": "Class IA phosphatidylinositol 3-kinases are indispensable for osteoclast + function by regulating cytoskeletal organization and cell death", "abstract": + null, "venue": "", "year": 2009, "referenceCount": 0, "citationCount": 1, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2009-05-01", "journal": {"volume": + "44", "name": "Bone"}, "authors": [{"authorId": "2108944170", "name": "Masaki + Nakamura"}, {"authorId": "5169247", "name": "Hironari Masuda"}, {"authorId": + "40651060", "name": "M. Iwasawa"}, {"authorId": "145429399", "name": "Y. Nagase"}, + {"authorId": "145103616", "name": "Takashi Nakamura"}, {"authorId": "2568535", + "name": "S. Kato"}, {"authorId": "5177377", "name": "K. Ueki"}, {"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "28278589", "name": "Kozo Nakamura"}, {"authorId": "144638767", + "name": "Sakae Tanaka"}]}, {"paperId": "a5d7657201d83a62dfcff93bd25e44b550c19973", + "externalIds": {"MAG": "2166472612", "DOI": "10.1126/science.1165069", "CorpusId": + 5358680, "PubMed": "19407199"}, "corpusId": 5358680, "publicationVenue": {"id": + "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": "journal", + "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/a5d7657201d83a62dfcff93bd25e44b550c19973", + "title": "Biomolecular Characterization and Protein Sequences of the Campanian + Hadrosaur B. canadensis", "abstract": "The Birds and the Dinosaurs The extent + to which primary tissues are preserved in ancient fossils remains controversial. + Schweitzer et al. (p. 626; see the news story by Service) describe well-preserved + tissues and primary collagen sequences from the femur of an 80-million-year-old + hadrosaur. The fossil preserved structures resembling primary bone tissues + and vessels. Both extracts and tissue pieces were analyzed in multiple laboratories + by mass spectrometry, which revealed ancient collagen sequences that support + a close relation between birds and dinosaurs. Analysis of well-preserved tissues + from an 80-million-year-old hadrosaur supports the dinosaur-bird relationship. + Molecular preservation in non-avian dinosaurs is controversial. We present + multiple lines of evidence that endogenous proteinaceous material is preserved + in bone fragments and soft tissues from an 80-million-year-old Campanian hadrosaur, + Brachylophosaurus canadensis [Museum of the Rockies (MOR) 2598]. Microstructural + and immunological data are consistent with preservation of multiple bone matrix + and vessel proteins, and phylogenetic analyses of Brachylophosaurus collagen + sequenced by mass spectrometry robustly support the bird-dinosaur clade, consistent + with an endogenous source for these collagen peptides. These data complement + earlier results from Tyrannosaurus rex (MOR 1125) and confirm that molecular + preservation in Cretaceous dinosaurs is not a unique event.", "venue": "Science", + "year": 2009, "referenceCount": 26, "citationCount": 206, "influentialCitationCount": + 6, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Environmental + Science", "source": "s2-fos-model"}, {"category": "Geography", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-05-01", "journal": {"volume": "324", "pages": "626 + - 631", "name": "Science"}, "authors": [{"authorId": "5618773", "name": "M. + Schweitzer"}, {"authorId": "7494304", "name": "Wenxia Zheng"}, {"authorId": + "143615392", "name": "C. Organ"}, {"authorId": "2988211", "name": "R. Avci"}, + {"authorId": "8048771", "name": "Z. Suo"}, {"authorId": "4333053", "name": + "Lisa M. Freimark"}, {"authorId": "5457987", "name": "V. LeBleu"}, {"authorId": + "1441583847", "name": "M. Duncan"}, {"authorId": "3804233", "name": "M. V. + Vander Heiden"}, {"authorId": "1400084319", "name": "J. Neveu"}, {"authorId": + "1400084865", "name": "William S. Lane"}, {"authorId": "48894637", "name": + "J. Cottrell"}, {"authorId": "1701498", "name": "J. Horner"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5090009", "name": "R. Kalluri"}, + {"authorId": "3028470", "name": "J. Asara"}]}, {"paperId": "a8e8da7ed4b92b24c45b889adb344b4e47aaace1", + "externalIds": {"MAG": "2165002727", "DOI": "10.1016/j.molcel.2008.12.026", + "CorpusId": 35835179, "PubMed": "19187764"}, "corpusId": 35835179, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/a8e8da7ed4b92b24c45b889adb344b4e47aaace1", + "title": "Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to + promote melanoma cell proliferation.", "abstract": null, "venue": "Molecules + and Cells", "year": 2009, "referenceCount": 62, "citationCount": 347, "influentialCitationCount": + 26, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276509000021/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2009-01-30", "journal": {"volume": + "33 2", "pages": "\n 237-47\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "143918840", "name": "B. Zheng"}, {"authorId": "46973400", + "name": "Joseph H. Jeong"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "48009853", "name": "Yuan Yuan"}, {"authorId": "6318792", "name": "S. Granter"}, + {"authorId": "144750835", "name": "L. Chin"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "af2dee0a2e3460fd1504377da271d63874d759e0", "externalIds": + {"MAG": "2030357707", "DOI": "10.1038/nbt1009-916", "CorpusId": 28569221, + "PubMed": "19816448"}, "corpusId": 28569221, "publicationVenue": {"id": "458166b3-de17-4bf3-bbbb-e53782de2f0f", + "name": "Nature Biotechnology", "type": "journal", "alternate_names": ["Nat + Biotechnol"], "issn": "1087-0156", "url": "http://www.nature.com/nbt/", "alternate_urls": + ["http://www.nature.com/nbt"]}, "url": "https://www.semanticscholar.org/paper/af2dee0a2e3460fd1504377da271d63874d759e0", + "title": "Cancer''s insatiable appetite", "abstract": null, "venue": "Nature + Biotechnology", "year": 2009, "referenceCount": 15, "citationCount": 47, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc3744822?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["News"], "publicationDate": "2009-10-01", "journal": {"volume": "27", "pages": + "916-917", "name": "Nature Biotechnology"}, "authors": [{"authorId": "2268976", + "name": "J. Locasale"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "35413264", "name": "M. V. Heiden"}]}, {"paperId": "b9fe6d51c45464cd999dd9bf01e85133f38d0c44", + "externalIds": {"CorpusId": 30217707}, "corpusId": 30217707, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b9fe6d51c45464cd999dd9bf01e85133f38d0c44", + "title": "Substrate specificity and inhibitors of LRRK 2 , a protein kinase + mutated in Parkinson \u2019 s disease", "abstract": "R. Jeremy NICHOLS*1, + Nicolas DZAMKO*, Jessica E. HUTTI\u2020\u2021, Lewis C. CANTLEY\u2020\u2021, + Maria DEAK*, Jennifer MORAN\u00a7, Paul BAMBOROUGH\u2016, Alastair D. REITH\u00b6 + and Dario R. ALESSI*1 *MRC Protein Phosphorylation Unit, College of Life Sciences, + University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K., \u2020Department + of Systems Biology, Harvard Medical School, Boston, MA 02115, U.S.A., \u2021Division + of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, + U.S.A., \u00a7Division of Signal Transduction Therapy Unit, College of Life + Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K., + \u2016Molecular Discovery Research, GlaxoSmithKline Pharmaceuticals R&D, Medicines + Research Centre, Gunnels Wood Road, Stevenage, Herts. SG1 2NY, U.K., and \u00b6Neurosciences + Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals R&D, + New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, U.K.", "venue": + "", "year": 2009, "referenceCount": 41, "citationCount": 26, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "36960808", + "name": "R. Nichols"}, {"authorId": "46728221", "name": "N. Dzamko"}, {"authorId": + "6742227", "name": "Jessica E. Hutti"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "4206645", "name": "M. De\u00e1k"}, {"authorId": "46717397", + "name": "Jennifer M. Moran"}, {"authorId": "8064952", "name": "P. Bamborough"}, + {"authorId": "46487022", "name": "A. Reith"}, {"authorId": "3475566", "name": + "D. Alessi"}]}, {"paperId": "c51823907e3cd5f6194907f9bc71d4c17299ea4b", "externalIds": + {"MAG": "2325532503", "DOI": "10.1158/0008-5472.FBCR09-IA-2", "CorpusId": + 75206763}, "corpusId": 75206763, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/c51823907e3cd5f6194907f9bc71d4c17299ea4b", + "title": "Abstract IA-2: PI3\u2010Kinase and cancer metabolism", "abstract": + null, "venue": "", "year": 2009, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2009-12-01", "journal": {"volume": + "69", "name": "Cancer Research"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "c5718d066904b280538c92596cab6c5ccca30d27", "externalIds": + {"MAG": "2012116166", "DOI": "10.1016/j.ccr.2009.06.006", "CorpusId": 206536589, + "PubMed": "19647222"}, "corpusId": 206536589, "publicationVenue": {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", + "name": "Cancer Cell", "type": "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/c5718d066904b280538c92596cab6c5ccca30d27", + "title": "Evidence that inositol polyphosphate 4-phosphatase type II is a + tumor suppressor that inhibits PI3K signaling.", "abstract": null, "venue": + "Cancer Cell", "year": 2009, "referenceCount": 52, "citationCount": 445, "influentialCitationCount": + 46, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1535610809001809/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2009-08-04", "journal": {"volume": + "16 2", "pages": "\n 115-25\n ", "name": "Cancer cell"}, "authors": + [{"authorId": "7739224", "name": "C. Gewinner"}, {"authorId": "2108217710", + "name": "Z. Wang"}, {"authorId": "145960454", "name": "A. Richardson"}, {"authorId": + "1396943744", "name": "J. Teruya-Feldstein"}, {"authorId": "4654839", "name": + "D. Etemadmoghadam"}, {"authorId": "2693074", "name": "D. Bowtell"}, {"authorId": + "49632549", "name": "J. Barretina"}, {"authorId": "3338634", "name": "William + M. Lin"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": "6316033", + "name": "L. Salmena"}, {"authorId": "4499580", "name": "P. Pandolfi"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "cdc7344063a4c8088a42b0b1023c961f553db60d", + "externalIds": {"MAG": "2168858265", "DOI": "10.1210/en.2009-0454", "CorpusId": + 1532541, "PubMed": "19819947"}, "corpusId": 1532541, "publicationVenue": {"id": + "c9a5576c-9a45-4071-ac6f-efa4d4d5b200", "name": "Endocrinology", "type": "journal", + "issn": "2510-1935", "alternate_issns": ["0013-7227"], "url": "http://endo.endojournals.org/"}, + "url": "https://www.semanticscholar.org/paper/cdc7344063a4c8088a42b0b1023c961f553db60d", + "title": "Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin + neurons contributes to the regulation of glucose homeostasis.", "abstract": + "Recent studies demonstrated a role for hypothalamic insulin and leptin action + in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin + (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) + signaling in these neurons blunts the acute effects of insulin and leptin + on POMC neuronal activity. In the current study, we investigated whether disruption + of PI3K signaling in POMC neurons alters normal glucose homeostasis using + mouse models designed to both increase and decrease PI3K-mediated signaling + in these neurons. We found that deleting p85alpha alone induced resistance + to diet-induced obesity. In contrast, deletion of the p110alpha catalytic + subunit of PI3K led to increased weight gain and adipose tissue along with + reduced energy expenditure. Independent of these effects, increased PI3K activity + in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling + resulted in impaired glucose regulation. These studies show that activity + of the PI3K pathway in POMC neurons is involved in not only normal energy + regulation but also glucose homeostasis.", "venue": "Endocrinology", "year": + 2009, "referenceCount": 69, "citationCount": 83, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://academic.oup.com/endo/article-pdf/150/11/4874/8998896/endo4874.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2009-11-01", "journal": {"volume": + "150 11", "pages": "\n 4874-82\n ", "name": "Endocrinology"}, + "authors": [{"authorId": "2111068085", "name": "Jennifer W. Hill"}, {"authorId": + "48615607", "name": "Yong Xu"}, {"authorId": "3725193", "name": "F. Preitner"}, + {"authorId": "153230305", "name": "M. Fukuda"}, {"authorId": "90176312", "name": + "You-Ree Cho"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "5201594", "name": "N. Balthasar"}, {"authorId": "5582429", "name": "R. Coppari"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1997179", "name": + "B. Kahn"}, {"authorId": "50985038", "name": "Jean J. Zhao"}, {"authorId": + "5905630", "name": "J. Elmquist"}]}, {"paperId": "cfed6a3c5be6b4a59b92463159757eb498645043", + "externalIds": {"MAG": "2016899606", "DOI": "10.1016/j.molcel.2009.04.031", + "CorpusId": 23156747, "PubMed": "19481526"}, "corpusId": 23156747, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/cfed6a3c5be6b4a59b92463159757eb498645043", + "title": "Phosphorylation of the tumor suppressor CYLD by the breast cancer + oncogene IKKepsilon promotes cell transformation.", "abstract": null, "venue": + "Molecules and Cells", "year": 2009, "referenceCount": 47, "citationCount": + 228, "influentialCitationCount": 14, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S109727650900313X/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-05-14", "journal": {"volume": "34 4", "pages": "\n 461-72\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "6742227", "name": "Jessica + E. Hutti"}, {"authorId": "5642912", "name": "R. Shen"}, {"authorId": "145759174", + "name": "Derek W. Abbott"}, {"authorId": "5858765", "name": "A. Zhou"}, {"authorId": + "46975075", "name": "K. Sprott"}, {"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "1890553", "name": "W. Hahn"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "d2cf3e93599561e919b1aa49734bead20075925d", "externalIds": + {"MAG": "2080452140", "DOI": "10.1038/nature08617", "CorpusId": 4414182, "PubMed": + "19935646"}, "corpusId": 4414182, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/d2cf3e93599561e919b1aa49734bead20075925d", + "title": "Cancer-associated IDH1 mutations produce 2-hydroxyglutarate", "abstract": + null, "venue": "Nature", "year": 2009, "referenceCount": 28, "citationCount": + 3302, "influentialCitationCount": 218, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc2818760?pdf=render", "status": + null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2009-12-10", "journal": + {"volume": "462", "pages": "739-744", "name": "Nature"}, "authors": [{"authorId": + "38799894", "name": "L. Dang"}, {"authorId": "143657476", "name": "D. White"}, + {"authorId": "144707828", "name": "S. Gross"}, {"authorId": "36199097", "name": + "B. Bennett"}, {"authorId": "3564730", "name": "M. Bittinger"}, {"authorId": + "4691854", "name": "E. Driggers"}, {"authorId": "4936699", "name": "V. Fantin"}, + {"authorId": "5240350", "name": "H. G. Jang"}, {"authorId": "5210229", "name": + "Shengfang Jin"}, {"authorId": "46624965", "name": "M. Keenan"}, {"authorId": + "145638995", "name": "K. Marks"}, {"authorId": "2148693", "name": "R. Prins"}, + {"authorId": "35327932", "name": "P. Ward"}, {"authorId": "4886372", "name": + "K. Yen"}, {"authorId": "5557307", "name": "L. Liau"}, {"authorId": "35264286", + "name": "J. Rabinowitz"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "31604076", "name": "C. Thompson"}, {"authorId": "35413264", "name": "M. V. + Heiden"}, {"authorId": "4297092", "name": "S. Su"}]}, {"paperId": "e0756852ed9fee5b05d0eb6dbd00272fd43cb987", + "externalIds": {"MAG": "1994961642", "DOI": "10.1002/dvdy.22078", "CorpusId": + 26322702, "PubMed": "19705443"}, "corpusId": 26322702, "publicationVenue": + {"id": "a4cd271c-e78f-486f-bf3c-c0c28f2cb575", "name": "Developmental Dynamics", + "type": "journal", "alternate_names": ["Dev Dyn"], "issn": "1058-8388", "url": + "http://www3.interscience.wiley.com/cgi-bin/jhome/109873231", "alternate_urls": + ["http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0177", "http://www3.interscience.wiley.com/cgi-bin/jhome/38417", + "https://onlinelibrary.wiley.com/journal/10970177"]}, "url": "https://www.semanticscholar.org/paper/e0756852ed9fee5b05d0eb6dbd00272fd43cb987", + "title": "Organ\u2010specific lymphangiectasia, arrested lymphatic sprouting, + and maturation defects resulting from gene\u2010targeting of the PI3K regulatory + isoforms p85\u03b1, p55\u03b1, and p50\u03b1", "abstract": "The phosphoinositide + 3\u2010kinase (PI3K) family has multiple vascular functions, but the specific + regulatory isoform supporting lymphangiogenesis remains unidentified. Here, + we report that deletion of the Pik3r1 gene, encoding the regulatory subunits + p85\u03b1, p55\u03b1, and p50\u03b1 impairs lymphatic sprouting and maturation, + and causes abnormal lymphatic morphology, without major impact on blood vessels. + Pik3r1 deletion had the most severe consequences among gut and diaphragm lymphatics, + which share the retroperitoneal anlage, initially suggesting that the Pik3r1 + role in this vasculature is anlage\u2010dependent. However, whereas lymphatic + sprouting toward the diaphragm was arrested, lymphatics invaded the gut, where + remodeling and valve formation were impaired. Thus, cell\u2010origin fails + to explain the phenotype. Only the gut showed lymphangiectasia, lymphatic + up\u2010regulation of the transforming growth factor\u2010\u03b2 co\u2010receptor + endoglin, and reduced levels of mature vascular endothelial growth factor\u2010C + protein. Our data suggest that Pik3r1 isoforms are required for distinct steps + of embryonic lymphangiogenesis in different organ microenvironments, whereas + they are largely dispensable for hemangiogenesis. Developmental Dynamics 238:2670\u20132679, + 2009. \u00a9 2009 Wiley\u2010Liss, Inc.", "venue": "Developmental Dynamics", + "year": 2009, "referenceCount": 57, "citationCount": 45, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/dvdy.22078", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-10-01", "journal": {"volume": "238", "name": "Developmental + Dynamics"}, "authors": [{"authorId": "1403487625", "name": "Carla Mouta-Bellum"}, + {"authorId": "145286026", "name": "A. Kirov"}, {"authorId": "1422447285", + "name": "Laura Miceli-Libby"}, {"authorId": "34369473", "name": "M. Mancini"}, + {"authorId": "2559122", "name": "T. Petrova"}, {"authorId": "145241025", "name": + "L. Liaw"}, {"authorId": "6057816", "name": "I. Prudovsky"}, {"authorId": + "13545505", "name": "P. Thorpe"}, {"authorId": "48246980", "name": "N. Miura"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4943908", "name": + "K. Alitalo"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "2800536", "name": "C. Vary"}]}, {"paperId": "f87313ac5400130b1c3e99cd8209835901dfdd69", + "externalIds": {"MAG": "2169903226", "DOI": "10.1016/j.cell.2008.11.044", + "CorpusId": 18141193, "PubMed": "19203585"}, "corpusId": 18141193, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/f87313ac5400130b1c3e99cd8209835901dfdd69", + "title": "Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy", + "abstract": null, "venue": "Cell", "year": 2009, "referenceCount": 59, "citationCount": + 1493, "influentialCitationCount": 92, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867408015195/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2009-02-06", "journal": {"volume": "136", "pages": "521-534", + "name": "Cell"}, "authors": [{"authorId": "2443785", "name": "P. Nicklin"}, + {"authorId": "153877611", "name": "Phil Bergman"}, {"authorId": "48335317", + "name": "Bailin Zhang"}, {"authorId": "5726884", "name": "E. Triantafellow"}, + {"authorId": "2155263853", "name": "Henry Wang"}, {"authorId": "5476944", + "name": "B. Nyfeler"}, {"authorId": "2118696793", "name": "Haidi Yang"}, {"authorId": + "3721603", "name": "M. Hild"}, {"authorId": "7636232", "name": "C. Kung"}, + {"authorId": "145013770", "name": "Christopher J. Wilson"}, {"authorId": "4436761", + "name": "V. Myer"}, {"authorId": "3706796", "name": "J. MacKeigan"}, {"authorId": + "46558196", "name": "Jeffrey A. Porter"}, {"authorId": "49416774", "name": + "Y. Wang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144774406", + "name": "P. Finan"}, {"authorId": "2561067", "name": "L. Murphy"}]}, {"paperId": + "14edeb5badfec455ef912d96dc7fd14bed170c40", "externalIds": {"MAG": "2164959077", + "CorpusId": 85845312}, "corpusId": 85845312, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/14edeb5badfec455ef912d96dc7fd14bed170c40", + "title": "Pyruvate kinase M2 is a phosphotyrosine", "abstract": null, "venue": + "", "year": 2008, "referenceCount": 14, "citationCount": 28, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": {"volume": "", "name": ""}, "authors": + [{"authorId": "4164415", "name": "H. Christofk"}, {"authorId": "35413264", + "name": "M. V. Heiden"}, {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "4864d3cbb670dfb271441da22fc76a964ca17371", "externalIds": {"MAG": + "2929737142", "CorpusId": 132138683}, "corpusId": 132138683, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/4864d3cbb670dfb271441da22fc76a964ca17371", + "title": "Activateurs de la pyruvate kinase m2 et proc\u00e9d\u00e9 de traitement + d''une maladie", "abstract": "La presente invention concerne des procedes, + des compositions, et des kits pour l''utilisation d''activateurs de la PKM2 + pour le traitement, la prevention, ou l''amelioration de maladies associees + a la fonction de la PKM2, comprenant par exemple le cancer, le diabete, l''atherosclerose, + la restenose, l''obesite, les troubles autoimmuns, et les troubles proliferatifs.", + "venue": "", "year": 2008, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}], "publicationTypes": + null, "publicationDate": "2008-08-18", "journal": null, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "35413264", "name": "M. V. + Heiden"}, {"authorId": "4164415", "name": "H. Christofk"}]}, {"paperId": "524fde341fed330eab2b1c34f44967c29cb47e4f", + "externalIds": {"MAG": "2069493334", "DOI": "10.1021/jm800374f", "CorpusId": + 31457919, "PubMed": "18630894"}, "corpusId": 31457919, "publicationVenue": + {"id": "4cce60a8-2106-4240-bece-fb6488df6bd1", "name": "Journal of Medicinal + Chemistry", "type": "journal", "alternate_names": ["J Med Chem"], "issn": + "0022-2623", "url": "https://pubs.acs.org/journal/jmcmar", "alternate_urls": + ["http://pubs.acs.org/journal/jmcmar", "http://pubs.acs.org/journals/jmcmar/index.html"]}, + "url": "https://www.semanticscholar.org/paper/524fde341fed330eab2b1c34f44967c29cb47e4f", + "title": "Slow self-activation enhances the potency of viridin prodrugs.", + "abstract": "When the viridin wortmannin (Wm) is modified by reaction with + certain nucleophiles at the C20 position, the compounds obtained exhibit an + improved antiproliferative activity even though a covalent reaction between + C20 and a lysine in the active site of PI3 kinase is essential to Wm''s ability + to inhibit this enzyme. Here we show that this improved potency results from + an intramolecular attack by the C6 hydroxyl group that slowly converts these + inactive prodrugs to the active species Wm over the 48 h duration of the antiproliferative + assay. Our results provide a guide for selecting Wm-like compounds to maximize + kinase inhibition with the variety of protocols used to assess the role of + PI3 kinase in biological systems, or for achieving optimal therapeutic effects + in vivo . In addition, the slow self-activation of WmC20 derivatives provides + a mechanism that can be exploited to obtain kinase inhibitors endowed with + physical and pharmacokinetic properties far different from man-made kinase + inhibitors because they do not bind to kinase active sites.", "venue": "Journal + of Medicinal Chemistry", "year": 2008, "referenceCount": 44, "citationCount": + 12, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc2663427?pdf=render", "status": + null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2008-08-14", "journal": {"volume": "51 15", "pages": "\n 4699-707\n ", + "name": "Journal of medicinal chemistry"}, "authors": [{"authorId": "37048404", + "name": "Joseph T. Blois"}, {"authorId": "6230104", "name": "Hushan Yuan"}, + {"authorId": "2109352731", "name": "Adam Smith"}, {"authorId": "5141475", + "name": "M. Pacold"}, {"authorId": "3127756", "name": "R. Weissleder"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5095505", "name": "L. Josephson"}]}, + {"paperId": "5a612171768a46cf6e97878c507c78401b773fcd", "externalIds": {"MAG": + "2512525477", "DOI": "10.1126/science.1157829", "CorpusId": 14077852, "PubMed": + "17431180"}, "corpusId": 14077852, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/5a612171768a46cf6e97878c507c78401b773fcd", + "title": "Response to Comment on \"Protein Sequences from Mastodon and Tyrannosaurus + rex Revealed by Mass Spectrometry\"", "abstract": "Endogenous peptide sequences + extracted from a 68-million-year-old Tyrannosaurus rex fossil bone and obtained + by mass spectrometry have been shown to be statistically significant based + on protein database searches using two different search engines and similarity + comparisons to authentic tandem mass spectrometry spectra. Specifically, we + have validated the sequence GVVGLP(OH)GQR.", "venue": "Science", "year": 2008, + "referenceCount": 44, "citationCount": 56, "influentialCitationCount": 8, + "isOpenAccess": true, "openAccessPdf": {"url": "http://doc.rero.ch/record/15738/files/PAL_E3010.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2008-08-22", "journal": {"volume": + "321", "pages": "1040 - 1040", "name": "Science"}, "authors": [{"authorId": + "3028470", "name": "J. Asara"}, {"authorId": "5618773", "name": "M. Schweitzer"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "48894637", "name": + "J. Cottrell"}]}, {"paperId": "5dadeeb7b1f02d8103a0d2263e39225c50e0c29f", + "externalIds": {"MAG": "2147246316", "DOI": "10.1002/pmic.200700426", "CorpusId": + 33178155, "PubMed": "18324724"}, "corpusId": 33178155, "publicationVenue": + {"id": "2c469df0-fa01-4dee-8f25-0d87a6fc4ef1", "name": "Proteomics", "type": + "journal", "issn": "1615-9853", "url": "http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1615-9861", + "alternate_urls": ["https://onlinelibrary.wiley.com/journal/16159861", "http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291615-9861", + "http://www.wiley-vch.de/publish/en/journals/alphabeticIndex/2120"]}, "url": + "https://www.semanticscholar.org/paper/5dadeeb7b1f02d8103a0d2263e39225c50e0c29f", + "title": "A label\u2010free quantification method by MS/MS TIC compared to + SILAC and spectral counting in a proteomics screen", "abstract": "In order + to assess the biological function of proteins and their modifications for + understanding signaling mechanisms within cells as well as specific biomarkers + to disease, it is important that quantitative information be obtained under + different experimental conditions. Stable isotope labeling is a powerful method + for accurately determining changes in the levels of proteins and PTMs; however, + isotope labeling experiments suffer from limited dynamic range resulting in + signal change ratios of less than \u223c20:1 using most commercial mass spectrometers. + Label\u2010free approaches to relative quantification in proteomics such as + spectral counting have gained popularity since no additional chemistries are + needed. Here, we show a label\u2010free method for relative quantification + based on the TIC from peptide MS/MS spectra collected from data\u2010dependent + runs can be used effectively as a quantitative measure and expands the dynamic + range over isotope labeling experiments allowing for abundance differences + up to \u223c60:1 in a screen for proteins that bind to phosphotyrosine residues.", + "venue": "Proteomics", "year": 2008, "referenceCount": 24, "citationCount": + 222, "influentialCitationCount": 7, "isOpenAccess": true, "openAccessPdf": + {"url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pmic.200700426", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "2008-03-01", "journal": {"volume": + "8", "name": "PROTEOMICS"}, "authors": [{"authorId": "3028470", "name": "J. + Asara"}, {"authorId": "4164415", "name": "H. Christofk"}, {"authorId": "4333053", + "name": "Lisa M. Freimark"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "68258db00627c0a1a2bc7398583dcabdc9d47abd", "externalIds": {"MAG": + "2071836703", "DOI": "10.1021/BC7002204", "CorpusId": 34703802, "PubMed": + "17988080"}, "corpusId": 34703802, "publicationVenue": {"id": "727c9075-57df-4276-83b3-a90e2722f883", + "name": "Bioconjugate chemistry", "type": "journal", "alternate_names": ["Bioconjugate + Chem", "Bioconjugate chem", "Bioconjugate Chemistry"], "issn": "1043-1802", + "url": "https://pubs.acs.org/journal/bcches", "alternate_urls": ["http://pubs.acs.org/journals/bcches/index.html", + "http://pubs.acs.org/journal/bcches"]}, "url": "https://www.semanticscholar.org/paper/68258db00627c0a1a2bc7398583dcabdc9d47abd", + "title": "Fate of a bioactive fluorescent wortmannin derivative in cells.", + "abstract": "Here, we report on NBD-Wm, a fluorescent wortmannin (Wm) probe + that maintains the bioactivity of Wm as an inhibitor of PI3 kinase and as + an antiproliferative agent. The attachment of the NBD fluorochrome permits + NBD-Wm in cells to be monitored by NBD fluorescence-based methods such as + FACS or fluorescence microscopy or with an anti-NBD antibody. The fluorescence + of NBD-Wm treated cells reached a peak at 1.5 h and then decreased because + of the extrusion of a fluorescent compound into the culture media. Cells accumulated + NBD-Wm to levels about 30-fold higher than those in the media. NBD-Wm modified + five major proteins, with the modification of the catalytic subunit of PI3 + kinase being a minor band. The bioactivity of NBD-Wm, coupled with a variety + of techniques available for determining its disposition, suggest that NBD-Wm + can be a useful tool in understanding the mechanism of action of viridins.", + "venue": "Bioconjugate chemistry", "year": 2008, "referenceCount": 0, "citationCount": + 16, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "19 1", "pages": "\n 130-7\n ", + "name": "Bioconjugate chemistry"}, "authors": [{"authorId": "40284134", "name": + "Katie R Barnes"}, {"authorId": "37048404", "name": "Joseph T. Blois"}, {"authorId": + "2109352731", "name": "Adam Smith"}, {"authorId": "6230104", "name": "Hushan + Yuan"}, {"authorId": "144649277", "name": "F. Reynolds"}, {"authorId": "3127756", + "name": "R. Weissleder"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5095505", "name": "L. Josephson"}]}, {"paperId": "6e302232969510d70881f3cac16960c2198c213a", + "externalIds": {"MAG": "2157983986", "DOI": "10.1172/JCI34739", "CorpusId": + 36856227, "PubMed": "18725988"}, "corpusId": 36856227, "publicationVenue": + {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", "name": "Journal of Clinical + Investigation", "type": "journal", "alternate_names": ["J Clin Investig"], + "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": ["http://www.jci.org/", + "https://www.jci.org/archive", "http://www.jci.org/impact"]}, "url": "https://www.semanticscholar.org/paper/6e302232969510d70881f3cac16960c2198c213a", + "title": "Inhibition of mTORC1 leads to MAPK pathway activation through a + PI3K-dependent feedback loop in human cancer.", "abstract": "Numerous studies + have established a causal link between aberrant mammalian target of rapamycin + (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may have + therapeutic potential. In this study, we show that rapamycin and its analogs + activate the MAPK pathway in human cancer, in what represents a novel mTORC1-MAPK + feedback loop. We found that tumor samples from patients with biopsy-accessible + solid tumors of advanced disease treated with RAD001, a rapamycin derivative, + showed an administration schedule-dependent increase in activation of the + MAPK pathway. RAD001 treatment also led to MAPK activation in a mouse model + of prostate cancer. We further show that rapamycin-induced MAPK activation + occurs in both normal cells and cancer cells lines and that this feedback + loop depends on an S6K-PI3K-Ras pathway. Significantly, pharmacological inhibition + of the MAPK pathway enhanced the antitumoral effect of mTORC1 inhibition by + rapamycin in cancer cells in vitro and in a xenograft mouse model. Taken together, + our findings identify MAPK activation as a consequence of mTORC1 inhibition + and underscore the potential of a combined therapeutic approach with mTORC1 + and MAPK inhibitors, currently employed as single agents in the clinic, for + the treatment of human cancers.", "venue": "Journal of Clinical Investigation", + "year": 2008, "referenceCount": 44, "citationCount": 1403, "influentialCitationCount": + 78, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jci.org/articles/view/34739/files/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2008-09-02", "journal": {"volume": "118 9", "pages": "\n 3065-74\n ", + "name": "The Journal of clinical investigation"}, "authors": [{"authorId": + "6988610", "name": "A. Carracedo"}, {"authorId": "2109875821", "name": "Li + Ma"}, {"authorId": "1396943744", "name": "J. Teruya-Feldstein"}, {"authorId": + "33614121", "name": "F. Rojo"}, {"authorId": "6316033", "name": "L. Salmena"}, + {"authorId": "34946126", "name": "A. Alimonti"}, {"authorId": "5135778", "name": + "Ainara Egia"}, {"authorId": "47742211", "name": "A. Sasaki"}, {"authorId": + "144125778", "name": "G. Thomas"}, {"authorId": "6542324", "name": "S. Kozma"}, + {"authorId": "5380009", "name": "A. Papa"}, {"authorId": "3547827", "name": + "C. Nardella"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "144806171", "name": "J. Baselga"}, {"authorId": "4499580", "name": "P. Pandolfi"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '238780' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:46 GMT + Via: + - 1.1 c440618d16cf0efe4e7b7ba6fc970474.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - e32BVuxIJ61kml2IrgdcN_kTuJKm0JNTHfyjWhEgPaUBPhBX7-Q_9w== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNObCFKSPHcF_4w= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '238780' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:46 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - 4a3d2483-7e01-4208-be7b-28cf44c2cdd2 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=500&limit=100 + response: + body: + string: '{"offset": 500, "next": 600, "data": [{"paperId": "7569b72221055030f3398c2326deaa13fd2201e1", + "externalIds": {"MAG": "2015207840", "DOI": "10.1038/nature06734", "CorpusId": + 16111842, "PubMed": "18337823"}, "corpusId": 16111842, "publicationVenue": + {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/7569b72221055030f3398c2326deaa13fd2201e1", + "title": "The M2 splice isoform of pyruvate kinase is important for cancer + metabolism and tumour growth", "abstract": null, "venue": "Nature", "year": + 2008, "referenceCount": 21, "citationCount": 2492, "influentialCitationCount": + 119, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2008-03-13", "journal": {"volume": "452", "pages": "230-233", "name": "Nature"}, + "authors": [{"authorId": "4164415", "name": "H. Christofk"}, {"authorId": + "35413264", "name": "M. V. Heiden"}, {"authorId": "4027329", "name": "M. Harris"}, + {"authorId": "46431693", "name": "A. Ramanathan"}, {"authorId": "1864575", + "name": "R. Gerszten"}, {"authorId": "2143698038", "name": "Ru Wei"}, {"authorId": + "2199934", "name": "M. Fleming"}, {"authorId": "2610390", "name": "S. Schreiber"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "7d18c2ffc32dc3aebb154d81d7610efdd3af0292", + "externalIds": {"MAG": "156118465", "DOI": "10.1096/fasebj.22.1_supplement.263.3", + "CorpusId": 82271172}, "corpusId": 82271172, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/7d18c2ffc32dc3aebb154d81d7610efdd3af0292", + "title": "Growth and survival signaling by lipid kinases", "abstract": "The + phosphoinositide 3\u2010kinase (PI3K) pathway plays a critical role in cell + growth regulation. PI3K generates the lipid, phosphatidylinositol\u20103,4,5\u2010trisphosphate + (PIP3), that acts as a membrane bound second messenger to activate AKT/PKB + family protein Ser/Thr kinases as well Tec family protein\u2010Tyr kinases. + PIP3 also regulates proteins that control Arf, Rac and Ras family GTP\u2010binding + proteins. This lipid is elevated in cancers, either due to loss of PTEN, the + phosphatases that degrades it, or due to constitutive PI3K activity because + of activating mutations in PIK3CA or an upstream activator of PI3K. The ultimate + consequence of activating PI3K is to generate changes in signaling networks + and gene expression patterns that promote cell growth, cell survival and cell + movement. In order to elucidate the role of the PI3K pathway in normal cell + growth and in cancer, we have generated mice in which genes for PI3K are deleted + or activated in specific tissues. In addition, we have investigated the biochemical + mechanisms by which PI3K becomes activated in human cancers. Our progress + in these areas will be summarized.", "venue": "", "year": 2008, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2008-03-01", "journal": {"volume": + "22", "name": "The FASEB Journal"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "81dcfe1ca61cc6f19bae5679eeafc5ad130fdaec", "externalIds": + {"MAG": "2073344794", "DOI": "10.1126/science.1154284", "CorpusId": 24971064, + "PubMed": "18436782"}, "corpusId": 24971064, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/81dcfe1ca61cc6f19bae5679eeafc5ad130fdaec", + "title": "Molecular Phylogenetics of Mastodon and Tyrannosaurus rex", "abstract": + "We report a molecular phylogeny for a nonavian dinosaur, extending our knowledge + of trait evolution within nonavian dinosaurs into the macromolecular level + of biological organization. Fragments of collagen \u03b11(I) and \u03b12(I) + proteins extracted from fossil bones of Tyrannosaurus rex and Mammut americanum + (mastodon) were analyzed with a variety of phylogenetic methods. Despite missing + sequence data, the mastodon groups with elephant and the T. rex groups with + birds, consistent with predictions based on genetic and morphological data + for mastodon and on morphological data for T. rex. Our findings suggest that + molecular data from long-extinct organisms may have the potential for resolving + relationships at critical areas in the vertebrate evolutionary tree that have, + so far, been phylogenetically intractable.", "venue": "Science", "year": 2008, + "referenceCount": 17, "citationCount": 55, "influentialCitationCount": 1, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2008-04-25", "journal": {"volume": "320", "pages": "499 - 499", "name": "Science"}, + "authors": [{"authorId": "143615392", "name": "C. Organ"}, {"authorId": "5618773", + "name": "M. Schweitzer"}, {"authorId": "7494304", "name": "Wenxia Zheng"}, + {"authorId": "4333053", "name": "Lisa M. Freimark"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "3028470", "name": "J. Asara"}]}, {"paperId": + "81f42c1dd1db0aeb2cc900799022c8453f126f7e", "externalIds": {"CorpusId": 57499592}, + "corpusId": 57499592, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/81f42c1dd1db0aeb2cc900799022c8453f126f7e", + "title": "Methods for treating cancer resistant to ErbB therapeutics", "abstract": + null, "venue": "", "year": 2008, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}], "publicationTypes": null, "publicationDate": null, + "journal": null, "authors": [{"authorId": "4147848", "name": "Pasi Antero + Janne"}, {"authorId": "6828387", "name": "Jeffrey A. Engelman"}, {"authorId": + "1723755", "name": "Lewis C. Cantley"}]}, {"paperId": "9e49004ea26397410420c71008c57f3c98c94a9a", + "externalIds": {"MAG": "2044823943", "DOI": "10.1016/j.cmet.2008.08.011", + "CorpusId": 31103050, "PubMed": "18762017"}, "corpusId": 31103050, "publicationVenue": + {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", "name": "Cell Metabolism", + "type": "journal", "alternate_names": ["Cell Metab"], "issn": "1550-4131", + "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": ["http://www.sciencedirect.com/science/journal/15504131", + "http://www.cellmetabolism.org/"]}, "url": "https://www.semanticscholar.org/paper/9e49004ea26397410420c71008c57f3c98c94a9a", + "title": "PI3K enters beta-testing.", "abstract": null, "venue": "Cell Metabolism", + "year": 2008, "referenceCount": 12, "citationCount": 10, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1550413108002520/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2008-09-03", "journal": + {"volume": "8 3", "pages": "\n 179-81\n ", "name": "Cell metabolism"}, + "authors": [{"authorId": "4635185", "name": "A. Shaywitz"}, {"authorId": "13782167", + "name": "K. Courtney"}, {"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "a2f90cbb3dd682c3ef2d38bfc880f4562a0ea8fe", + "externalIds": {"PubMedCentral": "2683415", "MAG": "2001999652", "DOI": "10.1038/nm.1890", + "CorpusId": 4961038, "PubMed": "19029981"}, "corpusId": 4961038, "publicationVenue": + {"id": "9e995b6d-f30b-4ab4-a13b-3dc2cc992f47", "name": "Nature Network Boston", + "type": "journal", "alternate_names": ["Nat Netw Boston", "Nat Med", "Nature + Medicine"], "issn": "1744-7933", "alternate_issns": ["1078-8956"], "url": + "https://www.nature.com/nature/articles?code=archive_news", "alternate_urls": + ["http://www.nature.com/news", "http://www.nature.com/nm/", "http://www.nature.com/nm/index.html"]}, + "url": "https://www.semanticscholar.org/paper/a2f90cbb3dd682c3ef2d38bfc880f4562a0ea8fe", + "title": "Effective Use of PI3K and MEK Inhibitors to Treat Mutant K-Ras G12D + and PIK3CA H1047R Murine Lung Cancers", "abstract": null, "venue": "Nature + Network Boston", "year": 2008, "referenceCount": 28, "citationCount": 1286, + "influentialCitationCount": 51, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc2683415?pdf=render", "status": null}, "fieldsOfStudy": + ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2008-11-30", "journal": + {"volume": "14", "pages": "1351 - 1356", "name": "Nature medicine"}, "authors": + [{"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "49330091", + "name": "Liang Chen"}, {"authorId": "46880153", "name": "X. Tan"}, {"authorId": + "50144013", "name": "K. Crosby"}, {"authorId": "145030722", "name": "A. Guimaraes"}, + {"authorId": "122354247", "name": "Rabi Upadhyay"}, {"authorId": "40159145", + "name": "Michel Maira"}, {"authorId": "6605449", "name": "K. McNamara"}, {"authorId": + "116397043", "name": "S. Perera"}, {"authorId": "4846062", "name": "Youngchul + Song"}, {"authorId": "6510669", "name": "L. Chirieac"}, {"authorId": "2274302", + "name": "R. Kaur"}, {"authorId": "5006113", "name": "Angela Lightbown"}, {"authorId": + "2028975460", "name": "Jessica Simendinger"}, {"authorId": "2109887600", "name": + "Timothy Q Li"}, {"authorId": "144315421", "name": "R. Padera"}, {"authorId": + "1401237414", "name": "C. Garc\u00eda-echeverr\u00eda"}, {"authorId": "3127756", + "name": "R. Weissleder"}, {"authorId": "2531456", "name": "U. Mahmood"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "32596484", "name": "Kwok-Kin + Wong"}]}, {"paperId": "a345de7c29c2552d519741dc949da6fd4c2c399e", "externalIds": + {"MAG": "2936425830", "CorpusId": 145854304}, "corpusId": 145854304, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/a345de7c29c2552d519741dc949da6fd4c2c399e", + "title": "Methods of treating resistant cancer therapeutic agents ERBB", "abstract": + "A therapeutic agent anti-ErbB and an anti-MET therapeutic agent for use in + treating a cancer in a subject that has developed resistance to treatment + with anti-ErbB therapeutic agent, wherein the subject has an amplification + of the MET gene wherein the anti-ErbB therapeutic agent is gefitinib, erlotinib, + lapatinib, PF00299804, CI-1033, EKB-569, BIBW2992, ZD6474, AV-412 or HKI-272, + and wherein the anti-MET therapeutic agent is PHA-665752, SU11274, SU5416, + PF-02341066, XL-880 or MGCD265.", "venue": "", "year": 2008, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2008-04-11", "journal": {"volume": "", "name": ""}, + "authors": [{"authorId": "4147848", "name": "P. Janne"}, {"authorId": "6828387", + "name": "J. Engelman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "ab43a7089bdc207e4b3ce3524beec97bac7ec1ea", "externalIds": {"MAG": "2923765412", + "CorpusId": 109101823}, "corpusId": 109101823, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/ab43a7089bdc207e4b3ce3524beec97bac7ec1ea", + "title": "Methods of treating cancer resistant to ErbB doctor mites", "abstract": + null, "venue": "", "year": 2008, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2008-04-11", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "4147848", "name": "P. Janne"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6828387", "name": + "J. Engelman"}]}, {"paperId": "c8e1d999171f446434bef4b2ab03cb4e59e8546d", + "externalIds": {"MAG": "1995444593", "DOI": "10.1038/nature06667", "CorpusId": + 4346405, "PubMed": "18337815"}, "corpusId": 4346405, "publicationVenue": {"id": + "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/c8e1d999171f446434bef4b2ab03cb4e59e8546d", + "title": "Pyruvate kinase M2 is a phosphotyrosine-binding protein", "abstract": + null, "venue": "Nature", "year": 2008, "referenceCount": 20, "citationCount": + 922, "influentialCitationCount": 51, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2008-03-13", "journal": {"volume": "452", "pages": "181-186", + "name": "Nature"}, "authors": [{"authorId": "4164415", "name": "H. Christofk"}, + {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": "2068343858", + "name": "Ning Wu"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "d02d36830d9140811a5b814d4dd28754ac2d45a1", + "externalIds": {"MAG": "2146414563", "DOI": "10.1038/onc.2008.245", "CorpusId": + 27772494, "PubMed": "18794884"}, "corpusId": 27772494, "publicationVenue": + {"id": "55bed249-d30f-456b-9d2c-a51dc149cb7a", "name": "Oncogene", "type": + "journal", "issn": "0950-9232", "url": "http://www.nature.com/onc/", "alternate_urls": + ["http://www.nature.com/onc", "http://www.naturesj.com/onc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/d02d36830d9140811a5b814d4dd28754ac2d45a1", + "title": "PI3K pathway alterations in cancer: variations on a theme", "abstract": + null, "venue": "Oncogene", "year": 2008, "referenceCount": 89, "citationCount": + 1768, "influentialCitationCount": 88, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3398461?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2008-09-18", "journal": {"volume": + "27", "pages": "5497-5510", "name": "Oncogene"}, "authors": [{"authorId": + "40062987", "name": "T. Yuan"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "e40f2444e9d18a0baf706ad43edc60b91909928e", "externalIds": {"MAG": + "2019962211", "DOI": "10.1073/pnas.0804123105", "CorpusId": 8189132, "PubMed": + "18621722"}, "corpusId": 8189132, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e40f2444e9d18a0baf706ad43edc60b91909928e", + "title": "Class 1A PI3K regulates vessel integrity during development and + tumorigenesis", "abstract": "PI3K is important in the regulation of growth, + proliferation, and survival of tumor cells. We show that class 1A PI3K is + also critical in the tumor microenvironment by regulating the integrity of + the tumor vasculature. Using Tie2Cre-mediated deletion of the PI3K regulatory + subunits (p85\u03b1, p55\u03b1, p50\u03b1, and p85\u03b2), we generated mice + with endothelial cell-specific loss of class 1A PI3K. Complete loss of all + subunits caused acute embryonic lethality at E11.5 due to hemorrhaging, whereas + retention of a single p85\u03b1 allele yielded viable mice that survived to + adulthood. These heterozygous mice exhibited no vascular defects until challenged + with a pathological insult, such as tumor cells or high levels of VEGF. Under + these pathological conditions, heterozygous mice exhibited localized vascular + abnormalities, including vessel leakage and the inability to maintain large + vessels, which caused a deceleration of tumorigenesis. Furthermore, we show + that a PI3K inhibitor can mimic the effects of class 1A PI3K loss, which suggests + that targeting class 1A PI3K may be a promising therapy for blocking tumor + angiogenesis.", "venue": "Proceedings of the National Academy of Sciences", + "year": 2008, "referenceCount": 38, "citationCount": 100, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/105/28/9739.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2008-07-15", "journal": {"volume": + "105", "pages": "9739 - 9744", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "40062987", "name": "T. Yuan"}, {"authorId": + "23597680", "name": "H. Choi"}, {"authorId": "8528956", "name": "A. Matsui"}, + {"authorId": "1714039", "name": "C. Benes"}, {"authorId": "144609942", "name": + "E. Lifshits"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "1788876", "name": "J. Frangioni"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "f064561b94c7355c7ee52e5c668032972cfb73e2", "externalIds": {"MAG": + "2098623033", "DOI": "10.1172/JCI32964", "CorpusId": 1269658, "PubMed": "18382766"}, + "corpusId": 1269658, "publicationVenue": {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", + "name": "Journal of Clinical Investigation", "type": "journal", "alternate_names": + ["J Clin Investig"], "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": + ["http://www.jci.org/", "https://www.jci.org/archive", "http://www.jci.org/impact"]}, + "url": "https://www.semanticscholar.org/paper/f064561b94c7355c7ee52e5c668032972cfb73e2", + "title": "Acute effects of leptin require PI3K signaling in hypothalamic proopiomelanocortin + neurons in mice.", "abstract": "Normal food intake and body weight homeostasis + require the direct action of leptin on hypothalamic proopiomelanocortin (POMC) + neurons. It has been proposed that leptin action requires PI3K activity. We + therefore assessed the contribution of PI3K signaling to leptin''s effects + on POMC neurons and organismal energy balance. Leptin caused a rapid depolarization + of POMC neurons and an increase in action potential frequency in patch-clamp + recordings of hypothalamic slices. Pharmacologic inhibition of PI3K prevented + this depolarization and increased POMC firing rate, indicating a PI3K-dependent + mechanism of leptin action. Mice with genetically disrupted PI3K signaling + in POMC cells failed to undergo POMC depolarization or increased firing frequency + in response to leptin. Insulin''s ability to hyperpolarize POMC neurons was + also abolished in these mice. Moreover, targeted disruption of PI3K blunted + the suppression of feeding elicited by central leptin administration. Despite + these differences, mice with impaired PI3K signaling in POMC neurons exhibited + normal long-term body weight regulation. Collectively, these results suggest + that PI3K signaling in POMC neurons is essential for leptin-induced activation + and insulin-induced inhibition of POMC cells and for the acute suppression + of food intake elicited by leptin, but is not a major contributor to the regulation + of long-term organismal energy homeostasis.", "venue": "Journal of Clinical + Investigation", "year": 2008, "referenceCount": 69, "citationCount": 339, + "influentialCitationCount": 22, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.jci.org/articles/view/32964/files/pdf", "status": null}, "fieldsOfStudy": + ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2008-05-01", "journal": + {"volume": "118 5", "pages": "\n 1796-805\n ", "name": "The + Journal of clinical investigation"}, "authors": [{"authorId": "2111068085", + "name": "Jennifer W. Hill"}, {"authorId": "145945266", "name": "K. Williams"}, + {"authorId": "2064450337", "name": "C. Ye"}, {"authorId": "145954100", "name": + "Ji Luo"}, {"authorId": "5201594", "name": "N. Balthasar"}, {"authorId": "5582429", + "name": "R. Coppari"}, {"authorId": "145855817", "name": "M. Cowley"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5942236", "name": "B. Lowell"}, + {"authorId": "5905630", "name": "J. Elmquist"}]}, {"paperId": "fc393db3315181e8a10087354b4a808fb2884b46", + "externalIds": {"MAG": "2111491167", "DOI": "10.1016/j.ccr.2008.04.008", "CorpusId": + 26918420, "PubMed": "18455118"}, "corpusId": 26918420, "publicationVenue": + {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", "name": "Cancer Cell", "type": + "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/fc393db3315181e8a10087354b4a808fb2884b46", + "title": "A sweet new role for EGFR in cancer.", "abstract": null, "venue": + "Cancer Cell", "year": 2008, "referenceCount": 14, "citationCount": 43, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1535610808001256/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["LettersAndComments", "JournalArticle"], "publicationDate": "2008-05-06", + "journal": {"volume": "13 5", "pages": "\n 375-6\n ", "name": + "Cancer cell"}, "authors": [{"authorId": "6828387", "name": "J. Engelman"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "09a4f384aa5e65ce85ee0b610f30c85a838b256e", + "externalIds": {"CorpusId": 88509816}, "corpusId": 88509816, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/09a4f384aa5e65ce85ee0b610f30c85a838b256e", + "title": "OBSERVATION AKT 1 Overexpression in Endothelial Cells Leads to the + Development of Cutaneous Vascular Malformations In Vivo", "abstract": "Background: + Vascular malformations are clinical disorders in which endothelial cells fail + to remodel and/or undergo programmed cell death, leading to abnormal persistence + of blood vessels. The abnormal persistence of vessels makes therapy difficult + because these lesions are resistant to interventions that are effective against + hemangiomas. Akt1 is a serine-threonine protein kinase, which is a key mediator + of resistance to programmed cell death. Our objective was to determine whether + sustained activation of Akt1 could lead to vascular malformation in mice.", + "venue": "", "year": 2007, "referenceCount": 16, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "3020797", + "name": "B. Perry"}, {"authorId": "5275632", "name": "J. Banyard"}, {"authorId": + "40057331", "name": "E. R. McLaughlin"}, {"authorId": "5456170", "name": "R. + Watnick"}, {"authorId": "35549806", "name": "Allie M. Sohn"}, {"authorId": + "3631923", "name": "D. Brindley"}, {"authorId": "3091430", "name": "T. Obata"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "27260993", "name": + "C. Cohen"}, {"authorId": "5860236", "name": "J. Arbiser"}]}, {"paperId": + "1e771985795efbdaf71e3cf7e9df5b616f9afe4d", "externalIds": {"MAG": "2520856817", + "DOI": "10.1097/01.JTO.0000283263.45841.E0", "CorpusId": 79424089}, "corpusId": + 79424089, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/1e771985795efbdaf71e3cf7e9df5b616f9afe4d", + "title": "D2-07: Mechanisms of activating PI3K signaling in lung cancers that + become resistant EGFR tyrosine kinase inhibitors", "abstract": null, "venue": + "", "year": 2007, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jto.org/article/S1556086415339794/pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2007-08-01", "journal": {"volume": + "2", "name": "Journal of Thoracic Oncology"}, "authors": [{"authorId": "6828387", + "name": "J. Engelman"}, {"authorId": "5610750", "name": "K. Zejnullahu"}, + {"authorId": "4441512", "name": "T. Mitsudomi"}, {"authorId": "40053421", + "name": "Courtney Hyland"}, {"authorId": "48490520", "name": "Joon-Oh Park"}, + {"authorId": "3734755", "name": "N. Lindeman"}, {"authorId": "77094637", "name": + "Christopher-Michael Gale"}, {"authorId": "2111027786", "name": "Xiaojun Zhao"}, + {"authorId": "2054179920", "name": "J. Christensen"}, {"authorId": "78976333", + "name": "Rogers M. Rogers"}, {"authorId": "3740336", "name": "F. Cappuzzo"}, + {"authorId": "17750315", "name": "T. Mok"}, {"authorId": "2118593740", "name": + "Charles Lee"}, {"authorId": "50138468", "name": "J. E. Bruce"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5984202", "name": "P. J\u00e4nne"}]}, + {"paperId": "1fea77a0309a94b75aaa07426c493f1ae088086a", "externalIds": {"MAG": + "2158668670", "DOI": "10.1128/MCB.01101-07", "CorpusId": 85675592}, "corpusId": + 85675592, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/1fea77a0309a94b75aaa07426c493f1ae088086a", + "title": "I\u03baB Kinase \u03b2 Phosphorylates the K63 Deubiquitinase A20 + To Cause Feedback Inhibition of the NF-\u03baB Pathway", "abstract": "ABSTRACT + Misregulation of NF-\u03baB signaling leads to infectious, inflammatory, or + autoimmune disorders. I\u03baB kinase \u03b2 (IKK\u03b2) is an essential activator + of NF-\u03baB and is known to phosphorylate the NF-\u03baB inhibitor, I\u03baB\u03b1, + allowing it to undergo ubiquitin-mediated proteasomal degradation. However, + beyond I\u03baB\u03b1, few additional IKK\u03b2 substrates have been identified. + Here we utilize a peptide library and bioinformatic approach to predict likely + substrates of IKK\u03b2. This approach predicted Ser381 of the K63 deubiquitinase + A20 as a likely site of IKK\u03b2 phosphorylation. While A20 is a known negative + regulator of innate immune signaling pathways, the mechanisms regulating the + activity of A20 are poorly understood. We show that IKK\u03b2 phosphorylates + A20 in vitro and in vivo at serine 381, and we further show that this phosphorylation + event increases the ability of A20 to inhibit the NF-\u03baB signaling pathway. + Phosphorylation of A20 by IKK\u03b2 thus represents part of a novel feedback + loop that regulates the duration of NF-\u03baB signaling following activation + of innate immune signaling pathways.", "venue": "Molecular and Cellular Biology", + "year": 2007, "referenceCount": 48, "citationCount": 138, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://mcb.asm.org/content/27/21/7451.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2007-08-20", "journal": {"volume": + "27", "pages": "7451 - 7461", "name": "Molecular and Cellular Biology"}, "authors": + [{"authorId": "6742227", "name": "Jessica E. Hutti"}, {"authorId": "25581223", + "name": "B. Turk"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "145400524", "name": "A. Ma"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "145759174", "name": "Derek W. Abbott"}]}, {"paperId": "20f54fa19322206148ef17adace42fc1469b0a0a", + "externalIds": {"CorpusId": 251342109}, "corpusId": 251342109, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/20f54fa19322206148ef17adace42fc1469b0a0a", + "title": "The p85 (cid:2) Regulatory Subunit of Phosphoinositide 3-Kinase + Potentiates c-Jun N-Terminal Kinase-Mediated Insulin Resistance (cid:1) \u2020", + "abstract": "Insulin resistance is a de\ufb01ning feature of type 2 diabetes + and the metabolic syndrome. While the molecular mechanisms of insulin resistance + are multiple, recent evidence suggests that attenuation of insulin signaling + by c-Jun N-terminal kinase (JNK) may be a central part of the pathobiology + of insulin resistance. Here we demonstrate that the p85 (cid:1) regulatory + subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin\u2019s + metabolic actions, is also required for the activation of JNK in states of + insulin resistance, including high-fat diet-induced obesity and JNK1 overexpression. + The requirement of the p85 (cid:1) regulatory subunit for JNK occurs independently + of its role as a component of the PI3K heterodimer and occurs only in response + to speci\ufb01c stimuli, namely, insulin and tunicamycin, a chemical that + induces endoplasmic reticulum stress. We further show that insulin and p85 + activate JNK by via cdc42 and MKK4. The activation of this cdc42/JNK pathway + requires both an intact N terminus and functional SH2 domains within the C + terminus of the p85 (cid:1) regulatory subunit. Thus, p85 (cid:1) plays a + dual role in regulating insulin sensitivity and may mediate cross talk between + the PI3K and stress kinase pathways.", "venue": "", "year": 2007, "referenceCount": + 58, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": null, "authors": [{"authorId": "48311527", "name": "C. Taniguchi"}, + {"authorId": "47567005", "name": "J. Alem\u00e1n"}, {"authorId": "5177377", + "name": "K. Ueki"}, {"authorId": "48300144", "name": "Jin-guang Luo"}, {"authorId": + "1928077", "name": "T. Asano"}, {"authorId": "4628208", "name": "H. Kaneto"}, + {"authorId": "1813278", "name": "G. Stephanopoulos"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "144391716", "name": "C. Kahn"}]}, {"paperId": + "220eb59e8fc484cc4a378113396635541edbf35d", "externalIds": {"MAG": "2927172772", + "CorpusId": 208370767}, "corpusId": 208370767, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/220eb59e8fc484cc4a378113396635541edbf35d", + "title": "Pyruvate kinase inhibitors and disease treatment methods", "abstract": + "A compound selected from ** Formula ** and salts thereof, for use in the + treatment of cancer, in which the cancer is selected from cancers of the breast, + prostate, lung, bronchial, colon, rectal, kidney, renal, skin, pelvic, pancreatic, + oral, ovary, head, neck, thyroid, parathyroid, stomach, gastrointestinal, + intestine (for example, thin and thick), brain, esophagus, liver, gallbladder, + pleura, intrahepatic bile ducts, cervix , testicular, ureter, anal, larynx, + pharynx, bone, articular, vulvar, eye and urinary bladder, non-Hodgkin lymphoma, + Hodgkin lymphoma, melanomas, carcinomas, basal cell carcinomas, neuroblastomas, + multiple myelomas, chronic lymphocytic leukemia, soft tissue cancers (eg, + heart), gastrointestinal stromal tumors, chronic myeloid leukemias, malignant + mesotheliomas, retinoblastomas and soft tissue sarcomas.", "venue": "", "year": + 2007, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2007-08-06", "journal": null, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "35413264", "name": "M. V. Heiden"}, {"authorId": + "4164415", "name": "H. Christofk"}]}, {"paperId": "240d0db8a1294a73ba68ded45c3963eccd838df9", + "externalIds": {"MAG": "2013185671", "DOI": "10.1016/J.CHEMBIOL.2007.02.007", + "CorpusId": 27730009, "PubMed": "17379147"}, "corpusId": 27730009, "publicationVenue": + {"id": "0c73784e-4058-48ce-b429-740c11d6f005", "name": "Chemistry and Biology", + "type": "journal", "alternate_names": ["Chemistry & Biology", "Chem Biology", + "Chem Biology"], "issn": "1074-5521", "alternate_issns": ["1879-1301"], "url": + "http://www.chembiol.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/10745521", + "https://www.journals.elsevier.com/chemistry-and-biology"]}, "url": "https://www.semanticscholar.org/paper/240d0db8a1294a73ba68ded45c3963eccd838df9", + "title": "Covalent reactions of wortmannin under physiological conditions.", + "abstract": null, "venue": "Chemistry and Biology", "year": 2007, "referenceCount": + 29, "citationCount": 30, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Chemistry", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2007-03-01", "journal": {"volume": "14 3", "pages": "\n 321-8\n ", + "name": "Chemistry & biology"}, "authors": [{"authorId": "6230104", "name": + "Hushan Yuan"}, {"authorId": "40284134", "name": "Katie R Barnes"}, {"authorId": + "3127756", "name": "R. Weissleder"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5095505", "name": "L. Josephson"}]}, {"paperId": "250a6b0b9d13e0fc334d95752e7eba556f70d616", + "externalIds": {"MAG": "2113561514", "DOI": "10.1128/MCB.00079-07", "CorpusId": + 35281735, "PubMed": "17283057"}, "corpusId": 35281735, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/250a6b0b9d13e0fc334d95752e7eba556f70d616", + "title": "The p85\u03b1 Regulatory Subunit of Phosphoinositide 3-Kinase Potentiates + c-Jun N-Terminal Kinase-Mediated Insulin Resistance", "abstract": "ABSTRACT + Insulin resistance is a defining feature of type 2 diabetes and the metabolic + syndrome. While the molecular mechanisms of insulin resistance are multiple, + recent evidence suggests that attenuation of insulin signaling by c-Jun N-terminal + kinase (JNK) may be a central part of the pathobiology of insulin resistance. + Here we demonstrate that the p85\u03b1 regulatory subunit of phosphoinositide + 3-kinase (PI3K), a key mediator of insulin''s metabolic actions, is also required + for the activation of JNK in states of insulin resistance, including high-fat + diet-induced obesity and JNK1 overexpression. The requirement of the p85\u03b1 + regulatory subunit for JNK occurs independently of its role as a component + of the PI3K heterodimer and occurs only in response to specific stimuli, namely, + insulin and tunicamycin, a chemical that induces endoplasmic reticulum stress. + We further show that insulin and p85 activate JNK by via cdc42 and MKK4. The + activation of this cdc42/JNK pathway requires both an intact N terminus and + functional SH2 domains within the C terminus of the p85\u03b1 regulatory subunit. + Thus, p85\u03b1 plays a dual role in regulating insulin sensitivity and may + mediate cross talk between the PI3K and stress kinase pathways.", "venue": + "Molecular and Cellular Biology", "year": 2007, "referenceCount": 55, "citationCount": + 77, "influentialCitationCount": 8, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc1899914?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2007-02-05", "journal": {"volume": "27", "pages": "2830 + - 2840", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "48311527", "name": "C. Taniguchi"}, {"authorId": "47567005", "name": "J. + Alem\u00e1n"}, {"authorId": "5177377", "name": "K. Ueki"}, {"authorId": "145954100", + "name": "Ji Luo"}, {"authorId": "1928077", "name": "T. Asano"}, {"authorId": + "4628208", "name": "H. Kaneto"}, {"authorId": "1813278", "name": "G. Stephanopoulos"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": + "C. Kahn"}]}, {"paperId": "2aa428e82908c5ce039df2fa36afb0c5e3d478bb", "externalIds": + {"MAG": "205636251", "DOI": "10.1182/BLOOD-2006-07-038620", "CorpusId": 3156314, + "PubMed": "17164340"}, "corpusId": 3156314, "publicationVenue": {"id": "9b6db04a-2990-4cf9-a14c-01d47636ee53", + "name": "Blood", "type": "journal", "issn": "0006-4971", "url": "http://www.bloodjournal.org/"}, + "url": "https://www.semanticscholar.org/paper/2aa428e82908c5ce039df2fa36afb0c5e3d478bb", + "title": "T-cell function is partially maintained in the absence of class + IA phosphoinositide 3-kinase signaling.", "abstract": "The class IA subgroup + of phosphoinositide 3-kinase (PI3K) is activated downstream of antigen receptors, + costimulatory molecules, and cytokine receptors on lymphocytes. Targeted deletion + of individual genes for class IA regulatory subunits severely impairs the + development and function of B cells but not T cells. Here we analyze conditional + mutant mice in which thymocytes and T cells lack the major class IA regulatory + subunits p85alpha, p55alpha, p50alpha, and p85beta. These cells exhibit nearly + complete loss of PI3K signaling downstream of the T-cell receptor (TCR) and + CD28. Nevertheless, T-cell development is largely unperturbed, and peripheral + T cells show only partial impairments in proliferation and cytokine production + in vitro. Both genetic and pharmacologic experiments suggest that class IA + PI3K signaling plays a limited role in T-cell proliferation driven by TCR/CD28 + clustering. In vivo, class IA-deficient T cells provide reduced help to B + cells but show normal ability to mediate antiviral immunity. Together these + findings provide definitive evidence that class IA PI3K regulatory subunits + are essential for a subset of T-cell functions while challenging the notion + that this signaling mechanism is a critical mediator of costimulatory signals + downstream of CD28.", "venue": "Blood", "year": 2007, "referenceCount": 76, + "citationCount": 61, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine", "Chemistry"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2007-04-01", "journal": {"volume": "109 7", "pages": "\n 2894-902\n ", + "name": "Blood"}, "authors": [{"authorId": "33653557", "name": "Jonathan A. + Deane"}, {"authorId": "152500082", "name": "M. Kharas"}, {"authorId": "39001132", + "name": "J. Oak"}, {"authorId": "40480164", "name": "Linda N. Stiles"}, {"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "34820441", "name": "T. Moore"}, + {"authorId": "143969328", "name": "H. Ji"}, {"authorId": "2892041", "name": + "C. Rommel"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2385578", "name": "T. Lane"}, {"authorId": "6241317", "name": "D. Fruman"}]}, + {"paperId": "2b970026aa91c43f5c37872358feb01425004e48", "externalIds": {"MAG": + "2064230121", "DOI": "10.1126/SCIENCE.1137614", "CorpusId": 85299309}, "corpusId": + 85299309, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/2b970026aa91c43f5c37872358feb01425004e48", + "title": "Protein Sequences from Mastodon and Tyrannosaurus Rex Revealed by + Mass Spectrometry", "abstract": "Fossilized bones from extinct taxa harbor + the potential for obtaining protein or DNA sequences that could reveal evolutionary + links to extant species. We used mass spectrometry to obtain protein sequences + from bones of a 160,000- to 600,000-year-old extinct mastodon (Mammut americanum) + and a 68-million-year-old dinosaur (Tyrannosaurus rex). The presence of T. + rex sequences indicates that their peptide bonds were remarkably stable. Mass + spectrometry can thus be used to determine unique sequences from ancient organisms + from peptide fragmentation patterns, a valuable tool to study the evolution + and adaptation of ancient taxa from which genomic sequences are unlikely to + be obtained.", "venue": "Science", "year": 2007, "referenceCount": 24, "citationCount": + 239, "influentialCitationCount": 5, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Geography", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2007-04-13", "journal": {"volume": "316", "pages": + "280 - 285", "name": "Science"}, "authors": [{"authorId": "3028470", "name": + "J. Asara"}, {"authorId": "5618773", "name": "M. Schweitzer"}, {"authorId": + "4333053", "name": "Lisa M. Freimark"}, {"authorId": "13194369", "name": "M. + Phillips"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "3386f902e4c9f0c6662884a94ce757b8d945a0a8", + "externalIds": {"CorpusId": 44657962, "PubMed": "17626872"}, "corpusId": 44657962, + "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": + "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], + "url": "https://www.jstor.org/journal/science", "alternate_urls": ["https://www.sciencemag.org/", + "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/3386f902e4c9f0c6662884a94ce757b8d945a0a8", + "title": "Biochemistry. PI3K charges ahead.", "abstract": null, "venue": "Science", + "year": 2007, "referenceCount": 0, "citationCount": 13, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}], "publicationTypes": + ["JournalArticle", "LettersAndComments"], "publicationDate": null, "journal": + {"volume": "317 5835", "pages": "\n 206-7\n ", "name": "Science"}, + "authors": [{"authorId": "46663676", "name": "Jennifer Y. Lee"}, {"authorId": + "6828387", "name": "J. Engelman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "398483c0f72d1766f871ca97d5fae789a8998229", "externalIds": {"MAG": + "1984621921", "DOI": "10.1016/j.cell.2007.06.009", "CorpusId": 9466184, "PubMed": + "17604717"}, "corpusId": 9466184, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/398483c0f72d1766f871ca97d5fae789a8998229", + "title": "AKT/PKB Signaling: Navigating Downstream", "abstract": null, "venue": + "Cell", "year": 2007, "referenceCount": 117, "citationCount": 5537, "influentialCitationCount": + 295, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867407007751/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2007-06-29", "journal": + {"volume": "129", "pages": "1261-1274", "name": "Cell"}, "authors": [{"authorId": + "2339651", "name": "B. Manning"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "39d0f03a9ecba0d92f7d252662ac40eeaec5afc9", "externalIds": {"MAG": + "2085927367", "DOI": "10.1001/ARCHDERM.143.4.504", "CorpusId": 17388466, "PubMed": + "17438183"}, "corpusId": 17388466, "publicationVenue": {"id": "686b1216-1c8e-48fa-ac90-53c43abc85de", + "name": "Archives of Dermatology", "type": "journal", "alternate_names": ["Arch + Dermatol", "A M A Archives of Dermatology", "M Arch Dermatol"], "issn": "0003-987X", + "alternate_issns": ["0096-5359"], "url": "http://archderm.ama-assn.org/contents-by-date.0.dtl"}, + "url": "https://www.semanticscholar.org/paper/39d0f03a9ecba0d92f7d252662ac40eeaec5afc9", + "title": "AKT1 overexpression in endothelial cells leads to the development + of cutaneous vascular malformations in vivo.", "abstract": "BACKGROUND\nVascular + malformations are clinical disorders in which endothelial cells fail to remodel + and/or undergo programmed cell death, leading to abnormal persistence of blood + vessels. The abnormal persistence of vessels makes therapy difficult because + these lesions are resistant to interventions that are effective against hemangiomas. + Akt1 is a serine-threonine protein kinase, which is a key mediator of resistance + to programmed cell death. Our objective was to determine whether sustained + activation of Akt1 could lead to vascular malformation in mice.\n\n\nOBSERVATIONS\nWe + examined the effect of constitutive activation of Akt1 in murine endothelial + cells (MS1 cells). Overexpression of active AKT1 in MS1 cells led to the development + of vascular malformations, characterized by wide endothelial lumens and minimal + investment of smooth muscle surrounding the vessels. The histologic features + of these vascular malformations is distinct from ras-transformed MS1 cells + (angiosarcoma) and suggest that differing signal abnormalities give rise to + human vascular malformations vs malignant vascular tumors.\n\n\nCONCLUSIONS\nInhibition + of Akt signaling may be useful in the treatment of vascular malformations. + Examination of problematic hemangiomas and vascular malformations for the + presence of activated Akt or downstream targets of Akt, such as mammalian + target of rapamycin (mTOR), may predict response to treatment with Akt inhibitors + or rapamycin. This study provides a potential rationale for the systemic and + topical use of these inhibitors for vascular malformations and hemangiomas.", + "venue": "Archives of Dermatology", "year": 2007, "referenceCount": 17, "citationCount": + 55, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://jamanetwork.com/journals/jamadermatology/articlepdf/412084/dob60044_504_506.pdf", + "status": null}, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Medicine", "source": "s2-fos-model"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2007-04-01", "journal": {"volume": "143 4", "pages": "\n 504-6\n ", + "name": "Archives of dermatology"}, "authors": [{"authorId": "3020797", "name": + "B. Perry"}, {"authorId": "5275632", "name": "J. Banyard"}, {"authorId": "40057331", + "name": "E. R. McLaughlin"}, {"authorId": "5456170", "name": "R. Watnick"}, + {"authorId": "35549806", "name": "Allie M. Sohn"}, {"authorId": "3631923", + "name": "D. Brindley"}, {"authorId": "3091430", "name": "T. Obata"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "27260993", "name": "C. Cohen"}, + {"authorId": "5860236", "name": "J. Arbiser"}]}, {"paperId": "4766c77e1a38110c5d7c1499c2a91c732ea9a448", + "externalIds": {"MAG": "2094309012", "DOI": "10.1016/J.MOLCEL.2007.02.012", + "CorpusId": 30670572, "PubMed": "17349956"}, "corpusId": 30670572, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/4766c77e1a38110c5d7c1499c2a91c732ea9a448", + "title": "Evolution of Ime2 phosphorylation sites on Cdk1 substrates provides + a mechanism to limit the effects of the phosphatase Cdc14 in meiosis.", "abstract": + null, "venue": "Molecules and Cells", "year": 2007, "referenceCount": 54, + "citationCount": 76, "influentialCitationCount": 12, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1097276507001128/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2007-03-09", "journal": {"volume": + "25 5", "pages": "\n 689-702\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "4344976", "name": "L. Holt"}, {"authorId": "6742227", + "name": "Jessica E. Hutti"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "35719273", "name": "D. Morgan"}]}, {"paperId": "658b36eb92235e85cacf11738c1f64d8cc5fccc9", + "externalIds": {"MAG": "2059839442", "DOI": "10.1073/pnas.0702663104", "CorpusId": + 19447508, "PubMed": "17483449"}, "corpusId": 19447508, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/658b36eb92235e85cacf11738c1f64d8cc5fccc9", + "title": "Deletion of the phosphoinositide 3-kinase p110\u03b3 gene attenuates + murine atherosclerosis", "abstract": "Inflammatory cell activation by chemokines + requires intracellular signaling through phosphoinositide 3-kinase (PI3-kinase) + and the PI3-kinase-dependent protein serine/threonine kinase Akt. Atherosclerosis + is a chronic inflammatory process driven by oxidatively modified (atherogenic) + lipoproteins, chemokines, and other agonists that activate PI3-kinase. Here + we show that macrophage PI3-kinase/Akt is activated by oxidized low-density + lipoprotein, inflammatory chemokines, and angiotensin II. This activation + is markedly reduced or absent in macrophages lacking p110\u03b3, the catalytic + subunit of class Ib PI3-kinase. We further demonstrate activation of macrophage/foam + cell PI3-kinase/Akt in atherosclerotic plaques from apolipoprotein E (apoE)-null + mice, which manifest an aggressive form of atherosclerosis, whereas activation + of PI3-kinase/Akt was undetectable in lesions from apoE-null mice lacking + p110\u03b3 despite the presence of class Ia PI3-kinase. Moreover, plaques + were significantly smaller in apoE\u2212/\u2212p110\u03b3\u2212/\u2212 mice + than in apoE\u2212/\u2212p110\u03b3+/+ or apoE\u2212/\u2212p110\u03b3+/\u2212mice + at all ages studied. In marked contrast to the embryonic lethality seen in + mice lacking class Ia PI3-kinase, germ-line deletion of p110\u03b3 results + in mice that exhibit normal viability, longevity, and fertility, with relatively + well tolerated defects in innate immune and inflammatory responses that may + play a role in diseases such as atherosclerosis and multiple sclerosis. Our + results not only shed mechanistic light on inflammatory signaling during atherogenesis, + but further identify p110\u03b3 as a possible target for pharmacological intervention + in the primary and secondary prevention of human atherosclerotic cardiovascular + disease.", "venue": "Proceedings of the National Academy of Sciences", "year": + 2007, "referenceCount": 38, "citationCount": 107, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1864909?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2007-05-08", "journal": {"volume": + "104", "pages": "8077 - 8082", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "2116093125", "name": "James D. Chang"}, + {"authorId": "4552671", "name": "G. Sukhova"}, {"authorId": "145096401", "name": + "P. Libby"}, {"authorId": "21192775", "name": "Eugenia Schvartz"}, {"authorId": + "4704909", "name": "A. Lichtenstein"}, {"authorId": "123039768", "name": "S. + Field"}, {"authorId": "144705393", "name": "Caitlin Kennedy"}, {"authorId": + "4302322", "name": "Swetha Madhavarapu"}, {"authorId": "145954100", "name": + "Ji Luo"}, {"authorId": "49709514", "name": "Dianqing Wu"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "65f5f4e3f5d0d854a404732f4163572033ca47a4", + "externalIds": {"MAG": "2069548854", "DOI": "10.1126/SCIENCE.317.5843.1324", + "CorpusId": 42564943, "PubMed": "17823333"}, "corpusId": 42564943, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/65f5f4e3f5d0d854a404732f4163572033ca47a4", + "title": "Interpreting Sequences from Mastodon and T. rex", "abstract": "J. + Asara et al. reported that collagen proteins from well-preserved ancient fossil + bones from a 160,000- to 600,000-year-old mastodon and a 68-million-year-old + T. rex can be extracted and sequenced (\u201cProtein sequences from mastodon + and Tyrannosaurus rex revealed by mass spectrometry,\u201d 13 April,", "venue": + "Science", "year": 2007, "referenceCount": 7, "citationCount": 42, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["LettersAndComments"], "publicationDate": + "2007-09-07", "journal": {"volume": "317", "pages": "1324 - 1325", "name": + "Science"}, "authors": [{"authorId": "3028470", "name": "J. Asara"}, {"authorId": + "2000634", "name": "J. Garavelli"}, {"authorId": "32424032", "name": "D. Slatter"}, + {"authorId": "5618773", "name": "M. Schweitzer"}, {"authorId": "4333053", + "name": "Lisa M. Freimark"}, {"authorId": "13194369", "name": "M. Phillips"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "79577f98f4e49d1e77e6c85fc9a0b8f139e62aa8", + "externalIds": {"MAG": "2116494541", "DOI": "10.1128/MCB.00270-07", "CorpusId": + 36865089, "PubMed": "17562858"}, "corpusId": 36865089, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/79577f98f4e49d1e77e6c85fc9a0b8f139e62aa8", + "title": "Coordinated Regulation of Toll-Like Receptor and NOD2 Signaling + by K63-Linked Polyubiquitin Chains", "abstract": "ABSTRACT K63 polyubiquitin + chains spatially and temporally link innate immune signaling effectors such + that cytokine release can be coordinated. Crohn''s disease is a prototypical + inflammatory disorder in which this process may be faulty as the major Crohn''s + disease-associated protein, NOD2 (nucleotide oligomerization domain 2), regulates + the formation of K63-linked polyubiquitin chains on the I kappa kinase (IKK) + scaffolding protein, NEMO (NF-\u03baB essential modifier). In this work, we + study these K63-linked ubiquitin networks to begin to understand the biochemical + basis for the signaling cross talk between extracellular pathogen Toll-like + receptors (TLRs) and intracellular pathogen NOD receptors. This work shows + that TLR signaling requires the same ubiquitination event on NEMO to properly + signal through NF-\u03baB. This ubiquitination is partially accomplished through + the E3 ubiquitin ligase TRAF6. TRAF6 is activated by NOD2, and this activation + is lost with a major Crohn''s disease-associated NOD2 allele, L1007insC. We + further show that TRAF6 and NOD2/RIP2 share the same biochemical machinery + (transforming growth factor \u03b2-activated kinase 1 [TAK1]/TAB/Ubc13) to + activate NF-\u03baB, allowing TLR signaling and NOD2 signaling to synergistically + augment cytokine release. These findings suggest a biochemical mechanism for + the faulty cytokine balance seen in Crohn''s disease.", "venue": "Molecular + and Cellular Biology", "year": 2007, "referenceCount": 53, "citationCount": + 181, "influentialCitationCount": 11, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc1952158?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2007-06-11", "journal": {"volume": "27", "pages": "6012 + - 6025", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "145759174", "name": "Derek W. Abbott"}, {"authorId": "2140143157", "name": + "Yibin Yang"}, {"authorId": "6742227", "name": "Jessica E. Hutti"}, {"authorId": + "4302322", "name": "Swetha Madhavarapu"}, {"authorId": "5739575", "name": + "M. Kelliher"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "99e5b842aec9d42221a7b315f168a92d7bd58413", "externalIds": {"MAG": "1998971866", + "DOI": "10.1126/science.1141478", "CorpusId": 23254145, "PubMed": "17463250"}, + "corpusId": 23254145, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/99e5b842aec9d42221a7b315f168a92d7bd58413", + "title": "MET Amplification Leads to Gefitinib Resistance in Lung Cancer by + Activating ERBB3 Signaling", "abstract": "The epidermal growth factor receptor + (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments + for lung cancers with EGFR activating mutations, but these tumors invariably + develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer + cell line that developed resistance to gefitinib as a result of focal amplification + of the MET proto-oncogene. inhibition of MET signaling in these cells restored + their sensitivity to gefitinib. MET amplification was detected in 4 of 18 + (22%) lung cancer specimens that had developed resistance to gefitinib or + erlotinib. We find that amplification of MET causes gefitinib resistance by + driving ERBB3 (HER3)\u2013dependent activation of PI3K, a pathway thought + to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification + may promote drug resistance in other ERBB-driven cancers as well.", "venue": + "Science", "year": 2007, "referenceCount": 24, "citationCount": 3518, "influentialCitationCount": + 239, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2007-05-18", "journal": {"volume": + "316", "pages": "1039 - 1043", "name": "Science"}, "authors": [{"authorId": + "6828387", "name": "J. Engelman"}, {"authorId": "5610750", "name": "K. Zejnullahu"}, + {"authorId": "4441512", "name": "T. Mitsudomi"}, {"authorId": "4846062", "name": + "Youngchul Song"}, {"authorId": "40053421", "name": "Courtney Hyland"}, {"authorId": + "48490520", "name": "Joon-Oh Park"}, {"authorId": "3734755", "name": "N. Lindeman"}, + {"authorId": "77094637", "name": "Christopher-Michael Gale"}, {"authorId": + "2111027786", "name": "Xiaojun Zhao"}, {"authorId": "2054179920", "name": + "J. Christensen"}, {"authorId": "2638484", "name": "T. Kosaka"}, {"authorId": + "48115918", "name": "A. Holmes"}, {"authorId": "35112344", "name": "A. Rogers"}, + {"authorId": "3740336", "name": "F. Cappuzzo"}, {"authorId": "17750315", "name": + "T. Mok"}, {"authorId": "2118593740", "name": "Charles Lee"}, {"authorId": + "115060139", "name": "B. Johnson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5984202", "name": "P. J\u00e4nne"}]}, {"paperId": "a616a4f6914c98ef7f423d4837fdba97d37345dd", + "externalIds": {"MAG": "1972115026", "DOI": "10.1016/S1359-6349(07)70219-7", + "CorpusId": 59087857}, "corpusId": 59087857, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/a616a4f6914c98ef7f423d4837fdba97d37345dd", + "title": "105 INVITED The role of PI3K in cancer", "abstract": null, "venue": + "", "year": 2007, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2007-09-01", "journal": {"volume": "5", "pages": "29", "name": "Ejc Supplements"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ad434f51de7468232a71d46398f1a0c10e0c84d5", + "externalIds": {"CorpusId": 30706377, "PubMed": "17709380"}, "corpusId": 30706377, + "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": + "Molecular and Cellular Biology", "type": "journal", "alternate_names": ["Mol + Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": + ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/ad434f51de7468232a71d46398f1a0c10e0c84d5", + "title": "IkappaB kinase beta phosphorylates the K63 deubiquitinase A20 to + cause feedback inhibition of the NF-kappaB pathway.", "abstract": "Misregulation + of NF-kappaB signaling leads to infectious, inflammatory, or autoimmune disorders. + IkappaB kinase beta (IKKbeta) is an essential activator of NF-kappaB and is + known to phosphorylate the NF-kappaB inhibitor, IkappaBalpha, allowing it + to undergo ubiquitin-mediated proteasomal degradation. However, beyond IkappaBalpha, + few additional IKKbeta substrates have been identified. Here we utilize a + peptide library and bioinformatic approach to predict likely substrates of + IKKbeta. This approach predicted Ser381 of the K63 deubiquitinase A20 as a + likely site of IKKbeta phosphorylation. While A20 is a known negative regulator + of innate immune signaling pathways, the mechanisms regulating the activity + of A20 are poorly understood. We show that IKKbeta phosphorylates A20 in vitro + and in vivo at serine 381, and we further show that this phosphorylation event + increases the ability of A20 to inhibit the NF-kappaB signaling pathway. Phosphorylation + of A20 by IKKbeta thus represents part of a novel feedback loop that regulates + the duration of NF-kappaB signaling following activation of innate immune + signaling pathways.", "venue": "Molecular and Cellular Biology", "year": 2007, + "referenceCount": 0, "citationCount": 84, "influentialCitationCount": 6, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "27 21", "pages": "\n 7451-61\n ", + "name": "Molecular and cellular biology"}, "authors": [{"authorId": "6742227", + "name": "Jessica E. Hutti"}, {"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "145400524", "name": + "A. Ma"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145759174", + "name": "Derek W. Abbott"}]}, {"paperId": "b6245f81d43ac9ccb0c8593eff19e8cadece8701", + "externalIds": {"MAG": "2049713190", "DOI": "10.1073/pnas.0610157104", "CorpusId": + 20223560, "PubMed": "17204563"}, "corpusId": 20223560, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/b6245f81d43ac9ccb0c8593eff19e8cadece8701", + "title": "Regulation of epithelial tight junction assembly and disassembly + by AMP-activated protein kinase", "abstract": "AMP-activated protein kinase + (AMPK) is a serine/threonine protein kinase that plays an important role in + maintaining cellular energy balance. The activity of AMPK is modulated both + by the cellular AMP-to-ATP ratio and by upstream kinases. Recently, AMPK was + shown to be phosphorylated and activated by LKB1, a protein kinase that plays + a conserved role in epithelial polarity regulation in mammals and Drosophila. + Here, we investigate the involvement of AMPK in the regulation of epithelial + tight junction assembly and cell polarization in MDCK cells. We show that + the level of AMPK phosphorylation increases during calcium-induced tight junction + assembly and cell polarization and that this increase depends on the kinase + activity of LKB1. Expression of a kinase-dead mutant of AMPK inhibits tight + junction assembly as indicated by measurement of transepithelial resistance + and analysis of ZO-1 localization to the tight junction after calcium switch. + Conversely, 5-aminoimidizole-4-carboxamide riboside, an activator of AMPK, + promotes transepithelial resistance development and tight junction assembly + upon calcium switch. Furthermore, 5-aminoimidizole-4-carboxamide riboside + partially protects the tight junctions from disassembly induced by calcium + depletion. These results support an important role of AMPK in the regulation + of epithelial tight junction assembly and disassembly and suggest an intriguing + link between cellular energy status and tight junction function.", "venue": + "Proceedings of the National Academy of Sciences", "year": 2007, "referenceCount": + 35, "citationCount": 261, "influentialCitationCount": 16, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1783397?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2007-01-16", "journal": {"volume": + "104", "pages": "819 - 822", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "143918840", "name": "B. Zheng"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "c65d1001e0e4bfa0816487259cdeabbbe52ecdb3", + "externalIds": {"CorpusId": 34475514}, "corpusId": 34475514, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/c65d1001e0e4bfa0816487259cdeabbbe52ecdb3", + "title": "Deletion of the phosphoinositide 3-kinase p 110 { gamma } gene attenuates + murine", "abstract": "www.pnas.org/cgi/content/full/104/19/8077#otherarticles + This article has been cited by other articles: E-mail Alerts . click here + at the top right corner of the article or Receive free email alerts when new + articles cite this article sign up in the box Rights & Permissions www.pnas.org/misc/rightperm.shtml + To reproduce this article in part (figures, tables) or in entirety, see: Reprints + www.pnas.org/misc/reprints.shtml To order reprints, see:", "venue": "", "year": + 2007, "referenceCount": 0, "citationCount": 8, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Art", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "2116093125", + "name": "James D. Chang"}, {"authorId": "4552671", "name": "G. Sukhova"}, + {"authorId": "145096401", "name": "P. Libby"}, {"authorId": "21192775", "name": + "Eugenia Schvartz"}, {"authorId": "4704909", "name": "A. Lichtenstein"}, {"authorId": + "123039768", "name": "S. Field"}, {"authorId": "144705393", "name": "Caitlin + Kennedy"}, {"authorId": "4302322", "name": "Swetha Madhavarapu"}, {"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "49709514", "name": "Dianqing + Wu"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "d102c6d3eee445e6dd1dd9a67dcfb4bb81ac32fb", + "externalIds": {"MAG": "1996894913", "DOI": "10.1073/pnas.0701179104", "CorpusId": + 28914577, "PubMed": "17372192"}, "corpusId": 28914577, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/d102c6d3eee445e6dd1dd9a67dcfb4bb81ac32fb", + "title": "Loss of the Par-1b/MARK2 polarity kinase leads to increased metabolic + rate, decreased adiposity, and insulin hypersensitivity in vivo", "abstract": + "Obesity is a major factor central to the development of insulin resistance + and type 2 diabetes. The identification and characterization of genes involved + in regulation of adiposity, insulin sensitivity, and glucose uptake are key + to the design and development of new drug therapies for this disease. In this + study, we show that the polarity kinase Par-1b/MARK2 is required for regulating + glucose metabolism in vivo. Mice null for Par-1b were lean, insulin hypersensitive, + resistant to high-fat diet-induced weight gain, and hypermetabolic. 18F-FDG + microPET and hyperinsulinemic\u2013euglycemic clamp analyses demonstrated + increased glucose uptake into white and brown adipose tissue, but not into + skeletal muscle of Par-1b null mice relative to wild-type controls. Taken + together, these data indicate that Par-1b is a regulator of glucose metabolism + and adiposity in the whole animal and may be a valuable drug target for the + treatment of both type 2 diabetes and obesity.", "venue": "Proceedings of + the National Academy of Sciences", "year": 2007, "referenceCount": 61, "citationCount": + 82, "influentialCitationCount": 3, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.pnas.org/content/104/13/5680.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2007-03-27", "journal": {"volume": "104", "pages": "5680 - 5685", "name": + "Proceedings of the National Academy of Sciences"}, "authors": [{"authorId": + "50139635", "name": "J. Hurov"}, {"authorId": "2112586271", "name": "Mei Huang"}, + {"authorId": "113240482", "name": "L. White"}, {"authorId": "6254704", "name": + "J. Lennerz"}, {"authorId": "2150789377", "name": "C. Choi"}, {"authorId": + "90176312", "name": "You-Ree Cho"}, {"authorId": "2109648507", "name": "Hyo-Jeong + Kim"}, {"authorId": "2255860", "name": "Julie L. Prior"}, {"authorId": "1421123275", + "name": "D. Piwnica-Worms"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1992964472", "name": "Jason K. Kim"}, {"authorId": "1856502", + "name": "G. Shulman"}, {"authorId": "1400810799", "name": "H. Piwnica-Worms"}]}, + {"paperId": "d491c5c39f591a1354b45e02b42381be0bfffb47", "externalIds": {"MAG": + "1766269169", "DOI": "10.1126/SCIENCE.1146073", "CorpusId": 84007363}, "corpusId": + 84007363, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/d491c5c39f591a1354b45e02b42381be0bfffb47", + "title": "PI3K Charges Ahead", "abstract": "Structural information about an + enzyme implicated in numerous cancers provides insights into to how certain + mutations promote cancer cell growth and survival.", "venue": "Science", "year": + 2007, "referenceCount": 8, "citationCount": 34, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2007-07-13", "journal": {"volume": "317", "pages": "206 - 207", "name": "Science"}, + "authors": [{"authorId": "46663676", "name": "Jennifer Y. Lee"}, {"authorId": + "6828387", "name": "J. Engelman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "34ec109c1f2d6271e870a10f4242c56ffd5a456b", "externalIds": {"MAG": + "2041600623", "DOI": "10.1038/nprot.2006.57", "CorpusId": 12433784, "PubMed": + "17406259"}, "corpusId": 12433784, "publicationVenue": {"id": "705a5f2b-aaf1-41fb-bc28-be78040b4587", + "name": "Nature Protocols", "type": "journal", "alternate_names": ["Nat Protoc"], + "issn": "1750-2799", "url": "https://www.nature.com/nprot/", "alternate_urls": + ["http://www.nature.com/nprot/index.html"]}, "url": "https://www.semanticscholar.org/paper/34ec109c1f2d6271e870a10f4242c56ffd5a456b", + "title": "Determining protein kinase substrate specificity by parallel solution-phase + assay of large numbers of peptide substrates", "abstract": null, "venue": + "Nature Protocols", "year": 2006, "referenceCount": 7, "citationCount": 73, + "influentialCitationCount": 4, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "1", "pages": "375-379", "name": + "Nature Protocols"}, "authors": [{"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "6742227", "name": "Jessica E. Hutti"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "36c79ddf639ff9a134b9512087375275de6266e4", + "externalIds": {"MAG": "2128368215", "DOI": "10.1038/sj.emboj.7601001", "CorpusId": + 41698564, "PubMed": "16482216"}, "corpusId": 41698564, "publicationVenue": + {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": + "journal", "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", + "url": "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/36c79ddf639ff9a134b9512087375275de6266e4", + "title": "PtdIns(5)P activates the host cell PI3\u2010kinase/Akt pathway during + Shigella flexneri infection", "abstract": null, "venue": "EMBO Journal", "year": + 2006, "referenceCount": 52, "citationCount": 213, "influentialCitationCount": + 16, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1409730?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2006-03-08", "journal": {"volume": + "25", "name": "The EMBO Journal"}, "authors": [{"authorId": "3397215", "name": + "C. Pendaries"}, {"authorId": "4511306", "name": "H. Tronch\u00e8re"}, {"authorId": + "3757633", "name": "L. Arbibe"}, {"authorId": "2228870", "name": "J. Mounier"}, + {"authorId": "6896988", "name": "O. Gozani"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "30565077", "name": "M. J. Fry"}, {"authorId": + "1398654140", "name": "F. Gaits\u2010Iacovoni"}, {"authorId": "10187502", + "name": "P. Sansonetti"}, {"authorId": "3933495", "name": "B. Payrastre"}]}, + {"paperId": "407c5a50c877726a242a00c162e97955b57e7537", "externalIds": {"MAG": + "2117780766", "DOI": "10.1158/1078-0432.CCR-06-0795", "CorpusId": 33401812, + "PubMed": "16857813"}, "corpusId": 33401812, "publicationVenue": {"id": "a360cd20-21d0-42cf-a0af-2f14e10514f0", + "name": "Clinical Cancer Research", "type": "journal", "alternate_names": + ["Clin Cancer Res"], "issn": "1078-0432", "url": "https://clincancerres.aacrjournals.org/", + "alternate_urls": ["http://clincancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/407c5a50c877726a242a00c162e97955b57e7537", + "title": "The Role of the ErbB Family Members in Non\u2013Small Cell Lung + Cancers Sensitive to Epidermal Growth Factor Receptor Kinase Inhibitors", + "abstract": "Inhibitors targeting the epidermal growth factor receptor (EGFR) + are effective in a subset of non\u2013small cell lung cancers. Such cancers + often harbor EGFR mutations and/or amplification. These cancers require EGFR + activity for the maintenance of critical intracellular survival and growth + signaling pathways. Evidence is now accruing that EGFR works in concert with + other ErbB family members, particularly HER2 and ErbB3, to activate these + signaling pathways in lung cancers. These findings have important implications + regarding the biology of these cancers and may lead to improved methods for + identifying tumors that are responsive to EGFR kinase inhibitors and alternative + therapies to treat cancers driven by ErbB signaling.", "venue": "Clinical + Cancer Research", "year": 2006, "referenceCount": 40, "citationCount": 90, + "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2006-07-15", "journal": {"volume": + "12", "pages": "4372s - 4376s", "name": "Clinical Cancer Research"}, "authors": + [{"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "43c9a351dd30d14912e840777e1115f4a7ef1a23", "externalIds": + {"MAG": "2060968396", "DOI": "10.1016/J.CMET.2006.04.005", "CorpusId": 24541977, + "PubMed": "16679292"}, "corpusId": 24541977, "publicationVenue": {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", + "name": "Cell Metabolism", "type": "journal", "alternate_names": ["Cell Metab"], + "issn": "1550-4131", "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/15504131", "http://www.cellmetabolism.org/"]}, + "url": "https://www.semanticscholar.org/paper/43c9a351dd30d14912e840777e1115f4a7ef1a23", + "title": "Divergent regulation of hepatic glucose and lipid metabolism by + phosphoinositide 3-kinase via Akt and PKClambda/zeta.", "abstract": null, + "venue": "Cell Metabolism", "year": 2006, "referenceCount": 32, "citationCount": + 275, "influentialCitationCount": 8, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S1550413106001240/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2006-05-01", "journal": {"volume": "3 5", "pages": "\n 343-53\n ", + "name": "Cell metabolism"}, "authors": [{"authorId": "48311527", "name": "C. + Taniguchi"}, {"authorId": "16114256", "name": "Tatsuya Kondo"}, {"authorId": + "3511388", "name": "M. Sajan"}, {"authorId": "145954100", "name": "Ji Luo"}, + {"authorId": "40803408", "name": "R. Bronson"}, {"authorId": "1928077", "name": + "T. Asano"}, {"authorId": "1601207486", "name": "R. Farese"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": "C. Kahn"}]}, + {"paperId": "4e054f477b96fe08f1efefe79aff0adc1d9171bd", "externalIds": {"MAG": + "2063578317", "DOI": "10.1073/pnas.0607984103", "CorpusId": 6113188, "PubMed": + "17071741"}, "corpusId": 6113188, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4e054f477b96fe08f1efefe79aff0adc1d9171bd", + "title": "Sj\u00f6gren''s syndrome-like disease in mice with T cells lacking + class 1A phosphoinositide-3-kinase", "abstract": "Sj\u00f6gren''s syndrome + (SS) is an autoimmune disease that is characterized by infiltration of exocrine + tissues, resulting in xerostomia (dry mouth) and keratoconjunctivitis sicca + (dry eyes). Here, we show that mice with T cell-specific loss of class IA + phosphoinositide 3-kinase function develop organ-specific autoimmunity that + resembles the human disease SS. Most mutant mice aged 3\u20138 months develop + corneal opacity and eye lesions due to irritation and constant scratching. + These mice display cardinal signs of primary SS such as marked lymphocytic + infiltration of the lacrimal glands, antinuclear antibodies in the serum, + and elevated titer of anti-SS-A antibody, in the absence of kidney pathology. + Immunofluorescence studies show the presence of numerous CD4+ T cells with + a smaller number of CD8+ T cells and B cells in the lacrimal glands. CD4+ + T cells from these mice exhibit aberrant differentiation in vitro. These results + indicate that aberrant T cells with impaired class IA phosphoinositide 3-kinase + signaling can lead to organ-specific autoimmunity. In addition, the mouse + model described here represents a tool to study the pathogenesis and treatment + of SS.", "venue": "Proceedings of the National Academy of Sciences", "year": + 2006, "referenceCount": 47, "citationCount": 71, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.pnas.org/content/103/45/16882.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2006-11-07", "journal": {"volume": "103", "pages": "16882 + - 16887", "name": "Proceedings of the National Academy of Sciences"}, "authors": + [{"authorId": "39001132", "name": "J. Oak"}, {"authorId": "33653557", "name": + "Jonathan A. Deane"}, {"authorId": "152500082", "name": "M. Kharas"}, {"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "2385578", "name": "T. Lane"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6241317", "name": + "D. Fruman"}]}, {"paperId": "62d195f01a47755743553ce3c8309551e1dca518", "externalIds": + {"MAG": "2008201842", "DOI": "10.1021/PR050334T", "CorpusId": 25498622, "PubMed": + "16396506"}, "corpusId": 25498622, "publicationVenue": {"id": "c7bbca07-9604-48a6-85d8-512fa663722e", + "name": "Journal of Proteome Research", "type": "journal", "alternate_names": + ["J Proteome Res"], "issn": "1535-3893", "url": "https://pubs.acs.org/journal/jprobs", + "alternate_urls": ["http://pubs.acs.org/journals/jprobs/", "http://pubs.acs.org/journals/jprobs/index.html", + "http://pubs.acs.org/journal/jprobs"]}, "url": "https://www.semanticscholar.org/paper/62d195f01a47755743553ce3c8309551e1dca518", + "title": "In-Gel Stable-Isotope Labeling (ISIL): a strategy for mass spectrometry-based + relative quantification.", "abstract": "Most proteomics approaches for relative + quantification of protein expression use a combination of stable-isotope labeling + and mass spectrometry. Traditionally, researchers have used difference gel + electrophoresis (DIGE) from stained 1D and 2D gels for relative quantification. + While differences in protein staining intensity can often be visualized, abundant + proteins can obscure less abundant proteins, and quantification of post-translational + modifications is difficult. A method is presented for quantifying changes + in the abundance of a specific protein or changes in specific modifications + of a protein using In-gel Stable-Isotope Labeling (ISIL). Proteins extracted + from any source (tissue, cell line, immunoprecipitate, etc.), treated under + two experimental conditions, are resolved in separate lanes by gel electrophoresis. + The regions of interest (visualized by staining) are reacted separately with + light versus heavy isotope-labeled reagents, and the gel slices are then mixed + and digested with proteases. The resulting peptides are then analyzed by LC-MS + to determine relative abundance of light/heavy isotope pairs and analyzed + by LC-MS/MS for identification of sequence and modifications. The strategy + compares well with other relative quantification strategies, and in silico + calculations reveal its effectiveness as a global relative quantification + strategy. An advantage of ISIL is that visualization of gel differences can + be used as a first quantification step followed by accurate and sensitive + protein level stable-isotope labeling and mass spectrometry-based relative + quantification.", "venue": "Journal of Proteome Research", "year": 2006, "referenceCount": + 14, "citationCount": 32, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": null, "journal": + {"volume": "5 1", "pages": "\n 155-63\n ", "name": "Journal + of proteome research"}, "authors": [{"authorId": "3028470", "name": "J. Asara"}, + {"authorId": "47958479", "name": "Xiang Zhang"}, {"authorId": "143918840", + "name": "B. Zheng"}, {"authorId": "12474335", "name": "Heather H Christofk"}, + {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "657b9110e5bf0f844d72de6ed0043af3bc9070a7", "externalIds": + {"MAG": "2144323242", "DOI": "10.1038/nature04869", "CorpusId": 4423556, "PubMed": + "16724053"}, "corpusId": 4423556, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/657b9110e5bf0f844d72de6ed0043af3bc9070a7", + "title": "Ras, PI(3)K and mTOR signalling controls tumour cell growth", "abstract": + null, "venue": "Nature", "year": 2006, "referenceCount": 86, "citationCount": + 2005, "influentialCitationCount": 76, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "2006-05-25", "journal": {"volume": + "441", "pages": "424-430", "name": "Nature"}, "authors": [{"authorId": "4426388", + "name": "R. Shaw"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "739f58805c5975a58bf0c59e82e4937d6c0091ec", "externalIds": {"MAG": "2091535117", + "DOI": "10.1016/J.CMET.2006.04.003", "CorpusId": 38432183, "PubMed": "16679293"}, + "corpusId": 38432183, "publicationVenue": {"id": "ad36b49e-5c03-4c48-be8d-321a0d17c2f6", + "name": "Cell Metabolism", "type": "journal", "alternate_names": ["Cell Metab"], + "issn": "1550-4131", "url": "https://www.cell.com/cell-metabolism/home", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/15504131", "http://www.cellmetabolism.org/"]}, + "url": "https://www.semanticscholar.org/paper/739f58805c5975a58bf0c59e82e4937d6c0091ec", + "title": "Loss of class IA PI3K signaling in muscle leads to impaired muscle + growth, insulin response, and hyperlipidemia.", "abstract": null, "venue": + "Cell Metabolism", "year": 2006, "referenceCount": 49, "citationCount": 107, + "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.cell.com/article/S1550413106001227/pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2006-05-01", "journal": + {"volume": "3 5", "pages": "\n 355-66\n ", "name": "Cell metabolism"}, + "authors": [{"authorId": "145954100", "name": "Ji Luo"}, {"authorId": "16248879", + "name": "Cassandra L Sobkiw"}, {"authorId": "6040440", "name": "M. Hirshman"}, + {"authorId": "143800250", "name": "M. Logsdon"}, {"authorId": "2109887600", + "name": "Timothy Q Li"}, {"authorId": "5766174", "name": "L. Goodyear"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "790cf5a1dcff8ea5e52429d08a1475ba00f18f56", + "externalIds": {"MAG": "2075342501", "DOI": "10.1073/pnas.0604628103", "CorpusId": + 45226883, "PubMed": "16880400"}, "corpusId": 45226883, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/790cf5a1dcff8ea5e52429d08a1475ba00f18f56", + "title": "Phosphoinositide 3-kinase regulatory subunit p85\u03b1 suppresses + insulin action via positive regulation of PTEN", "abstract": "The phosphoinositide + 3-kinase (PI3K) pathway is central to the metabolic actions of insulin on + liver. Here, we show that mice with a liver-specific deletion of the p85\u03b1 + regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement + of hepatic and peripheral insulin sensitivity. Although PI3K enzymatic activity + is diminished in L-Pik3r1KO livers because of a reduced level of regulatory + and catalytic subunits of PI3K, insulin-stimulated Akt activity is actually + increased. This increased Akt activity correlates with increased phosphatidylinositol + (3,4,5)-trisphosphate levels which are due, at least in part, to diminished + activity of the (3,4,5)-trisphosphate phosphatase PTEN. Thus, the regulatory + subunit p85\u03b1 is a critical modulator of insulin sensitivity in vivo not + only because of its effects on PI3K activation, but also as a regulator of + PTEN activity.", "venue": "Proceedings of the National Academy of Sciences", + "year": 2006, "referenceCount": 31, "citationCount": 153, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1524929?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2006-08-08", "journal": {"volume": + "103", "pages": "12093 - 12097", "name": "Proceedings of the National Academy + of Sciences"}, "authors": [{"authorId": "48311527", "name": "C. Taniguchi"}, + {"authorId": "3500862", "name": "T. Tran"}, {"authorId": "16114256", "name": + "Tatsuya Kondo"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "5177377", "name": "K. Ueki"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "144391716", "name": "C. Kahn"}]}, {"paperId": "79314bb75bcb4dc30abe0daba154b391ae5dbf0f", + "externalIds": {"MAG": "2106507395", "PubMedCentral": "1334198", "DOI": "10.1371/journal.pbio.0040038", + "CorpusId": 4844154, "PubMed": "16417406"}, "corpusId": 4844154, "publicationVenue": + {"id": "83ff973b-8a0e-4e00-a06a-2cfd9e222de9", "name": "PLoS Biology", "type": + "journal", "alternate_names": ["Plo Biology", "PLOS Biology", "PLO Biology"], + "issn": "1544-9173", "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=212", + "alternate_urls": ["http://www.plosbiology.org/", "https://journals.plos.org/plosbiology/"]}, + "url": "https://www.semanticscholar.org/paper/79314bb75bcb4dc30abe0daba154b391ae5dbf0f", + "title": "Hem-1 Complexes Are Essential for Rac Activation, Actin Polymerization, + and Myosin Regulation during Neutrophil Chemotaxis", "abstract": "Migrating + cells need to make different actin assemblies at the cell''s leading and trailing + edges and to maintain physical separation of signals for these assemblies. + This asymmetric control of activities represents one important form of cell + polarity. There are significant gaps in our understanding of the components + involved in generating and maintaining polarity during chemotaxis. Here we + characterize a family of complexes (which we term leading edge complexes), + scaffolded by hematopoietic protein 1 (Hem-1), that organize the neutrophil''s + leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous + protein (WAVE)2 complex, which mediates activation of actin polymerization + by Rac, is only one member of this family. A subset of these leading edge + complexes are biochemically separable from the WAVE2 complex and contain a + diverse set of potential polarity-regulating proteins. RNA interference\u2013mediated + knockdown of Hem-1\u2013containing complexes in neutrophil-like cells: (a) + dramatically impairs attractant-induced actin polymerization, polarity, and + chemotaxis; (b) substantially weakens Rac activation and phosphatidylinositol-(3,4,5)-tris-phosphate + production, disrupting the (phosphatidylinositol-(3,4,5)-tris-phosphate)/Rac/F-actin\u2013mediated + feedback circuit that organizes the leading edge; and (c) prevents exclusion + of activated myosin from the leading edge, perhaps by misregulating leading + edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken + together, these observations show that versatile Hem-1\u2013containing complexes + coordinate diverse regulatory signals at the leading edge of polarized neutrophils, + including but not confined to those involving WAVE2-dependent actin polymerization.", + "venue": "PLoS Biology", "year": 2006, "referenceCount": 90, "citationCount": + 172, "influentialCitationCount": 13, "isOpenAccess": true, "openAccessPdf": + {"url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0040038&type=printable", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2006-01-24", "journal": {"volume": "4", "name": "PLoS + Biology"}, "authors": [{"authorId": "3528639", "name": "O. Weiner"}, {"authorId": + "6306375", "name": "Maike C Rentel"}, {"authorId": "2069916342", "name": "A. + Ott"}, {"authorId": "2219979", "name": "G. Brown"}, {"authorId": "6432355", + "name": "Mark P. Jedrychowski"}, {"authorId": "88402408", "name": "M. Yaffe"}, + {"authorId": "2665934", "name": "S. Gygi"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2324026", "name": "H. Bourne"}, {"authorId": + "40294231", "name": "M. Kirschner"}]}, {"paperId": "7f76e9cde19b22ad1a25856f78f24c30dc6c6801", + "externalIds": {"MAG": "2068244265", "DOI": "10.1172/JCI28656", "CorpusId": + 23034765, "PubMed": "16906227"}, "corpusId": 23034765, "publicationVenue": + {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", "name": "Journal of Clinical + Investigation", "type": "journal", "alternate_names": ["J Clin Investig"], + "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": ["http://www.jci.org/", + "https://www.jci.org/archive", "http://www.jci.org/impact"]}, "url": "https://www.semanticscholar.org/paper/7f76e9cde19b22ad1a25856f78f24c30dc6c6801", + "title": "Allelic dilution obscures detection of a biologically significant + resistance mutation in EGFR-amplified lung cancer.", "abstract": "EGFR is + frequently mutated and amplified in lung adenocarcinomas sensitive to EGFR + inhibitors gefitinib and erlotinib. A secondary mutation, T790M, has been + associated with acquired resistance but has not been shown to be sufficient + to render EGFR mutant/amplified lung cancers resistant to EGFR inhibitors. + We created a model for studying acquired resistance to gefitinib by prolonged + exposure of a gefitinib-sensitive lung carcinoma cell line (H3255; EGFR mutated + and amplified) to gefitinib in vitro. The resulting resistant cell line acquired + a T790M mutation in a small fraction of the amplified alleles that was undetected + by direct sequencing and identified only by a highly sensitive HPLC-based + technique. In gefitinib-sensitive lung cancer cells with EGFR mutations and + amplifications, exogenous introduction of EGFR T790M effectively conferred + resistance to gefitinib and continued ErbB-3/PI3K/Akt signaling when in cis + to an activating mutation. Moreover, continued activation of PI3K signaling + by the PIK3CA oncogenic mutant, p110alpha E545K, was sufficient to abrogate + gefitinib-induced apoptosis. These findings suggest that allelic dilution + of biologically significant resistance mutations may go undetected by direct + sequencing in cancers with amplified oncogenes and that restoration of PI3K + activation via either a T790M mutation or other mechanisms can provide resistance + to gefitinib.", "venue": "Journal of Clinical Investigation", "year": 2006, + "referenceCount": 55, "citationCount": 456, "influentialCitationCount": 25, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jci.org/articles/view/28656/files/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2006-10-02", "journal": {"volume": + "116 10", "pages": "\n 2695-706\n ", "name": "The Journal + of clinical investigation"}, "authors": [{"authorId": "6828387", "name": "J. + Engelman"}, {"authorId": "4944777", "name": "T. Mukohara"}, {"authorId": "5610750", + "name": "K. Zejnullahu"}, {"authorId": "144609942", "name": "E. Lifshits"}, + {"authorId": "39319608", "name": "A. Borras"}, {"authorId": "77094637", "name": + "Christopher-Michael Gale"}, {"authorId": "3808694", "name": "G. Naumov"}, + {"authorId": "2127357", "name": "B. Yeap"}, {"authorId": "7844726", "name": + "E. Jarrell"}, {"authorId": "2110677231", "name": "J. Sun"}, {"authorId": + "35925520", "name": "S. Tracy"}, {"authorId": "2111027786", "name": "Xiaojun + Zhao"}, {"authorId": "2192944576", "name": "J. Heymach"}, {"authorId": "115060139", + "name": "B. Johnson"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5984202", "name": "P. J\u00e4nne"}]}, {"paperId": "9153cf9b582d9d3c686ae014fb8130a20d94a898", + "externalIds": {"MAG": "2009886463", "DOI": "10.1038/nrg1879", "CorpusId": + 19832477, "PubMed": "16847462"}, "corpusId": 19832477, "publicationVenue": + {"id": "f44976b5-2cb9-402a-bc59-6a174239987b", "name": "Nature reviews genetics", + "type": "journal", "alternate_names": ["Nature Reviews Genetics", "Nat rev + genet", "Nat Rev Genet"], "issn": "1471-0056", "url": "https://www.nature.com/nrg/", + "alternate_urls": ["http://www.nature.com/nrg/index.html"]}, "url": "https://www.semanticscholar.org/paper/9153cf9b582d9d3c686ae014fb8130a20d94a898", + "title": "The evolution of phosphatidylinositol 3-kinases as regulators of + growth and metabolism", "abstract": null, "venue": "Nature reviews genetics", + "year": 2006, "referenceCount": 171, "citationCount": 2957, "influentialCitationCount": + 179, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "2006-08-01", "journal": {"volume": "7", "pages": "606-619", "name": "Nature + Reviews Genetics"}, "authors": [{"authorId": "6828387", "name": "J. Engelman"}, + {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "ca3bf8fab2360c5efd323a6ce9441f280886d55a", "externalIds": + {"MAG": "2103919441", "DOI": "10.1021/BI052252O", "CorpusId": 5695487, "PubMed": + "16548514"}, "corpusId": 5695487, "publicationVenue": {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", + "name": "Biochemistry", "type": "journal", "issn": "0006-2960", "alternate_issns": + ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", "alternate_urls": + ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/ca3bf8fab2360c5efd323a6ce9441f280886d55a", + "title": "MMP-20 is predominately a tooth-specific enzyme with a deep catalytic + pocket that hydrolyzes type V collagen.", "abstract": "Matrix metalloproteinase-20 + (MMP-20, enamelysin) has a highly restricted pattern of expression. In healthy + tissues, MMP-20 is observed in the enamel organ and pulp organ of developing + teeth and is present only as an activated enzyme. To identify other tissues + that may express MMP-20, we performed a systematic mouse tissue expression + screen. Among the non-tooth tissues assayed, MMP-20 transcripts were identified + only in minute quantities within the large intestine. The murine Mmp20 promoter + was cloned, sequenced, and assessed for potential tooth-specific regulatory + elements. In silico analysis identified four promoter modules that were common + to Mmp20 and at least two of three coregulated predominantly tooth-specific + genes that encode ameloblastin, amelogenin, and enamelin. We asked if the + highly restricted MMP-20 expression pattern was associated with a broad substrate + specificity that might preclude its expression in other tissues. An iterative + mixture-based random doedecamer peptide library screen with Edman sequencing + of MMP-20 cleavage products revealed that, among MMPs previously screened, + MMP-20 had unique substrate preferences. These preferences indicate that MMP-20 + has a deep and wide catalytic pocket that can accommodate substrates with + large aromatic residues in the P1'' position. On the basis of matrices derived + from the peptide library data, we identified and then confirmed that type + V collagen is an MMP-20 substrate. Since type V collagen is not present in + dental enamel but is an otherwise widely distributed collagen, and since only + active MMP-20 has been observed in teeth, our data suggest that control of + MMP-20 activity is primarily regulated by transcriptional means.", "venue": + "Biochemistry", "year": 2006, "referenceCount": 65, "citationCount": 39, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2536712?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2006-03-28", "journal": {"volume": + "45 12", "pages": "\n 3863-74\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "25581223", "name": "B. Turk"}, {"authorId": "143876402", + "name": "Daniel H Lee"}, {"authorId": "3290904", "name": "Y. Yamakoshi"}, + {"authorId": "2332760", "name": "A. Klingenhoff"}, {"authorId": "1911457", + "name": "E. Reichenberger"}, {"authorId": "1400404078", "name": "J. T. Wright"}, + {"authorId": "3110446", "name": "J. Simmer"}, {"authorId": "50560564", "name": + "J. Komisarof"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "38065324", "name": "J. D. Bartlett"}]}, {"paperId": "cf3da94e66e95c7b055538d46c3e7fccc4f9ae4a", + "externalIds": {"MAG": "2528261300", "DOI": "10.1182/BLOOD-2005-07-2755", + "CorpusId": 15728726, "PubMed": "16434494"}, "corpusId": 15728726, "publicationVenue": + {"id": "9b6db04a-2990-4cf9-a14c-01d47636ee53", "name": "Blood", "type": "journal", + "issn": "0006-4971", "url": "http://www.bloodjournal.org/"}, "url": "https://www.semanticscholar.org/paper/cf3da94e66e95c7b055538d46c3e7fccc4f9ae4a", + "title": "Characterization of the megakaryocyte demarcation membrane system + and its role in thrombopoiesis.", "abstract": "To produce blood platelets, + megakaryocytes elaborate proplatelets, accompanied by expansion of membrane + surface area and dramatic cytoskeletal rearrangements. The invaginated demarcation + membrane system (DMS), a hallmark of mature cells, has been proposed as the + source of proplatelet membranes. By direct visualization of labeled DMS, we + demonstrate that this is indeed the case. Late in megakaryocyte ontogeny, + the DMS gets loaded with PI-4,5-P(2), a phospholipid that is confined to plasma + membranes in other cells. Appearance of PI-4,5-P(2) in the DMS occurs in proximity + to PI-5-P-4-kinase alpha (PIP4Kalpha), and short hairpin (sh) RNA-mediated + loss of PIP4Kalpha impairs both DMS development and expansion of megakaryocyte + size. Thus, PI-4,5-P(2) is a marker and possibly essential component of internal + membranes. PI-4,5-P(2) is known to promote actin polymerization by activating + Rho-like GTPases and Wiskott-Aldrich syndrome (WASp) family proteins. Indeed, + PI-4,5-P(2) in the megakaryocyte DMS associates with filamentous actin. Expression + of a dominant-negative N-WASp fragment or pharmacologic inhibition of actin + polymerization causes similar arrests in proplatelet formation, acting at + a step beyond expansion of the DMS and cell mass. These observations collectively + suggest a signaling pathway wherein PI-4,5-P(2) might facilitate DMS development + and local assembly of actin fibers in preparation for platelet biogenesis.", + "venue": "Blood", "year": 2006, "referenceCount": 60, "citationCount": 200, + "influentialCitationCount": 11, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2006-05-15", "journal": {"volume": "107 10", "pages": + "\n 3868-75\n ", "name": "Blood"}, "authors": [{"authorId": + "145453589", "name": "H. Schulze"}, {"authorId": "4263913", "name": "M. Korpal"}, + {"authorId": "50139635", "name": "J. Hurov"}, {"authorId": "2109704632", "name": + "Sang-We Kim"}, {"authorId": "2108045556", "name": "Jinghang Zhang"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144437468", "name": "T. Graf"}, + {"authorId": "2785025", "name": "R. Shivdasani"}]}, {"paperId": "fb8aeddb1c5c3b63de79c08be81becf99dbcd6b3", + "externalIds": {"MAG": "2081328577", "DOI": "10.1038/nprot.2006.7", "CorpusId": + 13055577, "PubMed": "17406210"}, "corpusId": 13055577, "publicationVenue": + {"id": "705a5f2b-aaf1-41fb-bc28-be78040b4587", "name": "Nature Protocols", + "type": "journal", "alternate_names": ["Nat Protoc"], "issn": "1750-2799", + "url": "https://www.nature.com/nprot/", "alternate_urls": ["http://www.nature.com/nprot/index.html"]}, + "url": "https://www.semanticscholar.org/paper/fb8aeddb1c5c3b63de79c08be81becf99dbcd6b3", + "title": "In-gel stable isotope labeling for relative quantification using + mass spectrometry", "abstract": null, "venue": "Nature Protocols", "year": + 2006, "referenceCount": 17, "citationCount": 14, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "1", "pages": "46-51", "name": "Nature Protocols"}, + "authors": [{"authorId": "3028470", "name": "J. Asara"}, {"authorId": "47958479", + "name": "Xiang Zhang"}, {"authorId": "143918840", "name": "B. Zheng"}, {"authorId": + "50399376", "name": "Lisa A Maroney"}, {"authorId": "4164415", "name": "H. + Christofk"}, {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "05e55d3b08a279dcabde2f50576ce5ab5f50b88b", + "externalIds": {"MAG": "1977443562", "DOI": "10.4161/cc.4.10.2062", "CorpusId": + 83542271}, "corpusId": 83542271, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/05e55d3b08a279dcabde2f50576ce5ab5f50b88b", + "title": "Then Negative Regulation of Phosphoinositide 3-Kinase Signaling + by p85 and Its Implication in Cancer", "abstract": "The phosphoinositide 3-kinase + (PI3K) signaling pathway critically regulates cell growth and cell survival. + Mutations that lead to aberrant activation of this pathway are frequent events + in human cancers. Here we discuss some recent studies identifying the mechanisms + by which p85, the regulatory subunit of PI3K, negatively regulates PI3K signaling. + While necessary for the stability and membrane recruitment of the p110 catalytic + subunit of PI3K. p85 represses the basal activity of p110 in the absence of + growth factor stimulation. In its unbound, free form, p85 sequesters the adaptor + protein IRS-1 and therefore limits the extent of PI3K signaling downstream + of the insulin and IGF-1 receptors. These findings lend new insight to how + changes in p85 gene dosage or mutations in p85 could lead to the hyper-activation + of PI3K and thus contribute towards tumorigenesis.", "venue": "", "year": + 2005, "referenceCount": 35, "citationCount": 79, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.tandfonline.com/doi/pdf/10.4161/cc.4.10.2062?needAccess=true", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2005-09-23", "journal": {"volume": + "4", "pages": "1309 - 1312", "name": "Cell Cycle"}, "authors": [{"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "20c3389ac3c7db80188e2d564de14cf9f1b6f035", "externalIds": {"MAG": + "2123933189", "DOI": "10.1128/MCB.25.21.9491-9502.2005", "CorpusId": 33188272, + "PubMed": "16227599"}, "corpusId": 33188272, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/20c3389ac3c7db80188e2d564de14cf9f1b6f035", + "title": "Class IA Phosphoinositide 3-Kinase Regulates Heart Size and Physiological + Cardiac Hypertrophy", "abstract": "ABSTRACT Class IA phosphoinositide 3-kinases + (PI3Ks) are activated by growth factor receptors, and they regulate, among + other processes, cell growth and organ size. Studies using transgenic mice + overexpressing constitutively active and dominant negative forms of the p110\u03b1 + catalytic subunit of class IA PI3K have implicated the role of this enzyme + in regulating heart size and physiological cardiac hypertrophy. To further + understand the role\u2009of class IA PI3K in controlling heart growth and + to circumvent potential complications from the overexpression of dominant + negative and constitutively active proteins, we generated mice with muscle-specific + deletion of the p85\u03b1 regulatory subunit and germ line deletion of the + p85\u03b2 regulatory subunit of class IA PI3K. Here we show that mice with + cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in + the heart, reduced heart size, and altered cardiac gene expression. Furthermore, + exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout + hearts. Despite such defects in postnatal developmental growth and physiological + hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial + histology. Our results therefore provide strong genetic evidence that class + IA PI3Ks are critical regulators for the developmental growth and physiological + hypertrophy of the heart.", "venue": "Molecular and Cellular Biology", "year": + 2005, "referenceCount": 63, "citationCount": 212, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1265829?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2005-11-01", "journal": {"volume": "25", "pages": "9491 + - 9502", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "6688807", "name": "J. McMullen"}, + {"authorId": "16248879", "name": "Cassandra L Sobkiw"}, {"authorId": "2152828772", + "name": "Li Zhang"}, {"authorId": "47130853", "name": "A. Dorfman"}, {"authorId": + "2697164", "name": "M. Sherwood"}, {"authorId": "143800250", "name": "M. Logsdon"}, + {"authorId": "40006904", "name": "J. Horner"}, {"authorId": "5593407", "name": + "R. DePinho"}, {"authorId": "47072554", "name": "S. Izumo"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "33fe9b71272dfd845d5c47d2b33cc144bb54bfd4", + "externalIds": {"CorpusId": 249519062}, "corpusId": 249519062, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/33fe9b71272dfd845d5c47d2b33cc144bb54bfd4", + "title": "Purification and characterization of human erythrocyte phosphatidylinositol + 4-kinase", "abstract": "Andrea GRAZIANI,*1I Leona E. LING,t Gerda ENDEMANN,T\u00b6 + Chris L. CARPENTER\u00a7 and Lewis C. CANTLEY* *Department of Physiology, + Tufts University School of Medicine, Boston, MA 021 11, U.S.A., tDana Farber + Cancer Institute, Boston, MA 02115, U.S.A., tDepartment of Cell Biology, Stanford + University School of Medicine, Stanford, CA 94305, U.S.A., and \u00a7Hematology-Oncology + Unit, Massachusetts General Hospital, Boston, MA 02114, U.S.A.", "venue": + "", "year": 2005, "referenceCount": 1, "citationCount": 2, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "2075627490", + "name": "Andrea"}, {"authorId": "89727637", "name": "Graziani"}, {"authorId": + "2084151248", "name": "Gerda"}, {"authorId": "2083062036", "name": "Endemann"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "3c7bc0c0f82e886656d0d531b9bd9bc1d0223739", + "externalIds": {"MAG": "2101778620", "DOI": "10.1093/JNCI/DJI238", "CorpusId": + 209530473}, "corpusId": 209530473, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/3c7bc0c0f82e886656d0d531b9bd9bc1d0223739", + "title": "Differential Effects of Gefitinib and Cetuximab on Non\u2013small-cell + Lung Cancers Bearing Epidermal Growth Factor Receptor Mutations", "abstract": + "BACKGROUND Many patients with non-small-cell lung cancer (NSCLC) who achieve + radiographic responses to treatment with the epidermal growth factor receptor + (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib have somatic mutations + in the EGFR tyrosine kinase domain. However, little is known about the efficacy + of cetuximab, an antibody against the EGFR extracellular domain, in EGFR mutant + NSCLC. METHODS NSCLC cell lines carrying wild-type EGFR (A549, H441, and H1666) + or mutant EGFR (H3255, DFCILU-011, PC-9, and HCC827) were treated with various + dilutions of gefitinib or cetuximab relative to maximal achievable serum concentration. + Cell growth was analyzed by the MTS assay, with differences between dose-response + curves analyzed nonparametrically. Apoptosis was analyzed by propidium iodide + staining and immunoblotting for PARP. Phosphorylation of EGFR and the downstream + signaling components ERK1/2 and Akt were analyzed by immunoblotting. Statistical + tests were two-sided. RESULTS Growth of NSCLC lines with wild-type EGFR was + slightly (A549 and H441) or moderately (H1666) inhibited by gefitinib and + cetuximab, and the effects of the two agents were similar. Both agents also + induced no (H441) or moderate (H1666) apoptosis in NSCLC cells with wild-type + EGFR. By contrast, gefitinib was statistically significantly more effective + than cetuximab at inhibiting growth of EGFR mutant cells (H3255: P = .003, + DFCILU-011: P = .011, and PC-9: P = .003), and gefitinib-treated EGFR mutant + cells had higher levels of apoptosis than cetuximab-treated cells (mean fold + increase in apoptosis by 1 microM of gefitinib and 10 microg/mL of cetuximab + relative to control, H3255: 8.3 [95% confidence interval {CI} = 4.8 to 11.8] + and 2.1 [95% CI = 2.0 to 2.2], respectively, P = .025; DFCILU-011: 5.7 [95% + CI = 5.1 to 6.3] and. 0.9 [95% CI = 0.3 to 1.5], respectively, P < .001). + Gefitinib treatment decreased EGFR, ERK1/2, and Akt phosphorylation in EGFR + mutant cell lines whereas cetuximab had relatively little effect. Both gefitinib + and cetuximab inhibited the growth of HCC827 cells, but gefitinib inhibited + growth to a greater extent (P = .003). CONCLUSIONS EGFR mutations in NSCLC + cells are associated with sensitivity to gefitinib but not to cetuximab.", + "venue": "", "year": 2005, "referenceCount": 45, "citationCount": 142, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2005-08-17", "journal": {"volume": "97", "pages": + "1185-1194", "name": "Journal of the National Cancer Institute"}, "authors": + [{"authorId": "4944777", "name": "T. Mukohara"}, {"authorId": "6828387", "name": + "J. Engelman"}, {"authorId": "35398614", "name": "N. Hanna"}, {"authorId": + "2127357", "name": "B. Yeap"}, {"authorId": "2109836647", "name": "S. Kobayashi"}, + {"authorId": "3734755", "name": "N. Lindeman"}, {"authorId": "3698254", "name": + "B. Halmos"}, {"authorId": "6927277", "name": "J. Pearlberg"}, {"authorId": + "46281629", "name": "Z. Tsuchihashi"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "5523919", "name": "D. Tenen"}, {"authorId": "115060139", + "name": "B. Johnson"}, {"authorId": "5984202", "name": "P. J\u00e4nne"}]}, + {"paperId": "3ff49b708fb6758ce6b63b33e0eaf98be6de83a9", "externalIds": {"PubMedCentral": + "2171479", "MAG": "2169058447", "DOI": "10.1083/jcb.200503088", "CorpusId": + 1390398, "PubMed": "16043515"}, "corpusId": 1390398, "publicationVenue": {"id": + "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/3ff49b708fb6758ce6b63b33e0eaf98be6de83a9", + "title": "The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates + IRS-1 signaling via the formation of a sequestration complex", "abstract": + "Phosphoinositide (PI) 3-kinase is required for most insulin and insulin-like + growth factor (IGF) 1\u2013dependent cellular responses. The p85 regulatory + subunit of PI 3-kinase is required to mediate the insulin-dependent recruitment + of PI 3-kinase to the plasma membrane, yet mice with reduced p85 expression + have increased insulin sensitivity. To further understand the role of p85, + we examined IGF-1\u2013dependent translocation of p85\u03b1 by using a green + fluorescence protein (GFP)\u2013tagged p85\u03b1 (EGFP\u2013p85\u03b1). In + response to IGF-1, but not to PDGF signaling, EGFP\u2013p85\u03b1 translocates + to discrete foci in the cell. These foci contain the insulin receptor substrate + (IRS) 1 adaptor molecule, and their formation requires the binding of p85 + to IRS-1. Surprisingly, monomeric p85 is preferentially localized to these + foci compared with the p85\u2013p110 dimer, and these foci are not sites of + phosphatidylinositol-3,4,5-trisphosphate production. Ultrastructural analysis + reveals that p85\u2013IRS-1 foci are cytosolic protein complexes devoid of + membrane. These results suggest a mechanism of signal down-regulation of IRS-1 + that is mediated by monomeric p85 through the formation of a sequestration + complex between p85 and IRS-1.", "venue": "Journal of Cell Biology", "year": + 2005, "referenceCount": 98, "citationCount": 150, "influentialCitationCount": + 6, "isOpenAccess": true, "openAccessPdf": {"url": "https://rupress.org/jcb/article-pdf/170/3/455/1320982/jcb1703455.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2005-08-01", "journal": {"volume": "170", "pages": "455 + - 464", "name": "The Journal of Cell Biology"}, "authors": [{"authorId": "145954100", + "name": "Ji Luo"}, {"authorId": "123039768", "name": "S. Field"}, {"authorId": + "46663676", "name": "Jennifer Y. Lee"}, {"authorId": "6828387", "name": "J. + Engelman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "4b6252344eb6005c24b6394815f7bb943294f350", + "externalIds": {"MAG": "2153518477", "DOI": "10.1016/S0169-5002(05)80475-1", + "CorpusId": 72975736}, "corpusId": 72975736, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/4b6252344eb6005c24b6394815f7bb943294f350", + "title": "PD-142 ErbB-3 mediates PI3K activity in gefitinib-sensitive non-smallcell + lung cancer cell lines", "abstract": null, "venue": "", "year": 2005, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2005-07-01", "journal": {"volume": + "49", "name": "Lung Cancer"}, "authors": [{"authorId": "6828387", "name": + "J. Engelman"}, {"authorId": "5984202", "name": "P. J\u00e4nne"}, {"authorId": + "145234673", "name": "C. Mermel"}, {"authorId": "6927277", "name": "J. Pearlberg"}, + {"authorId": "4944777", "name": "T. Mukohara"}, {"authorId": "39554977", "name": + "C. Fleet"}, {"authorId": "6306836", "name": "K. Cichowski"}, {"authorId": + "115060139", "name": "B. Johnson"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "4cca7d6b25989ff0e8d91199ed73048670936849", "externalIds": {"CorpusId": + 13581290}, "corpusId": 13581290, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4cca7d6b25989ff0e8d91199ed73048670936849", + "title": "Oncogenic in Mammary Epithelial Cells Mutations Are PIK 3 CA Associated + \u2212 Breast Cancer", "abstract": "Activation of the phosphoinositide 3-kinase + (PI3K) pathway has been implicated in the pathogenesis of a variety of cancers. + Recently, mutations in the gene encoding the p110A catalytic subunit of PI3K + (PIK3CA) have been identified in several human cancers. The mutations primarily + result in single amino acid substitutions, with >85% of the mutations in either + exon 9 or 20. Multiple studies have shown that these mutations are observed + in 18% to 40% of breast cancers. However, the phenotypic effects of these + PIK3CA mutations have not been examined in breast epithelial cells. Herein, + we examine the activity of the two most common variants, E545K and H1047R, + in the MCF-10A immortalized breast epithelial cell line. Both variants display + higher PI3K activity than wild-type p110A yet remain sensitive to pharmacologic + PI3K inhibition. In addition, expression of p110A mutants in mammary epithelial + cells induces multiple phenotypic alterations characteristic of breast tumor + cells, including anchorage-independent proliferation in soft agar, growth + factor\u2013independent proliferation, and protection from anoikis. Expression + of these mutant p110A isoforms also confers increased resistance to paclitaxel + and induces abnormal mammary acinar morphogenesis in three-dimensional basement + membrane cultures. Together, these data support the notion that the cancer-associated + mutations in PIK3CA may significantly contribute to breast cancer pathogenesis + and represent attractive targets for therapeutic inhibition. (Cancer Res 2005; + 65(23): 10992-11000)", "venue": "", "year": 2005, "referenceCount": 57, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + null, "authors": [{"authorId": "4327978", "name": "S. Isakoff"}, {"authorId": + "6828387", "name": "J. Engelman"}, {"authorId": "49807003", "name": "H. Irie"}, + {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": "3710358", "name": + "S. Brachmann"}, {"authorId": "3679091", "name": "R. Pearline"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3471778", "name": "J. Brugge"}]}, + {"paperId": "52707f333e8c6c5b254cc38561dc39500924e027", "externalIds": {"MAG": + "2401341245", "CorpusId": 221222794}, "corpusId": 221222794, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/52707f333e8c6c5b254cc38561dc39500924e027", + "title": "Marine source \u03c9-3 fatty acid, docosahexaenoic acid (DHA), inhibits + human colorectal cancer growth through multiple mechanisms depending on the + mutational status of p53 protein", "abstract": "5569 Epidemiological data + and previous in vivo and in vitro studies in our lab have suggested that diets + rich in \u03c9-3 polyunsaturated fatty acids (PUFAs) are inversely related + to human colorectal cancer growth. In addition, those studies revealed that + DHA was the primary tumor inhibiting \u03c9-3 fatty acid compared to EPA. + Using flow cytometry and spectrophotometric techniques, proliferation and + apoptosis assays were performed on two human colorectal cancer cell lines, + WiDr and COLO 205, which possess mutated and wild type p53 protein respectively, + treated with linoleic acid (LA), eicosapentaenoic acid (EPA) and DHA in vitro. + The study showed that DHA induced apoptosis in COLO 205 and only inhibited + cell proliferation in WiDr. EPA did not induce apoptotic events nor inhibit + cell proliferation in both cell lines although it inhibited cell growth by + 30%. To confirm an involvement of p53 protein in the growth inhibition exerted + by DHA, a p53 inhibitor, Pifithrin-\u03b1, was employed and the growth inhibition + of DHA treated COLO 205 but not WiDr cells was reversed with the inhibitor + treatment. To further elucidate mechanisms of the growth inhibition, levels + of phospho- shc, JNK and ERK which play major roles in the regulation of cell + proliferation and apoptosis, were measured in the both cell lines. fatty acid + treated WiDr cells exhibited lower levels of phospho- shc and ERK proteins, + but not JNK. In contrast, levels of phospho-JNK were lower in DHA treated + COLO 205 cells, but phosphorylation levels of other two proteins were not + altered. We have demonstrated that the growth inhibitory effect of DHA is + mediated through a p53 pathway when the tumor possesses a wild type protein. + In the tumor line possessing a mutated p53, DHA caused decrease in cell proliferation + through an inhibition of the MAPK signaling pathway. EPA does not activate + the p53 pathway. These different mechanism of actions may be the cause for + differential potencies between DHA and EPA. In addition, we have demonstrated + that DHA possesses tumor inhibiting activity in tumors with wild type and + mutated p53.", "venue": "", "year": 2005, "referenceCount": 0, "citationCount": + 1, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2005-05-01", "journal": {"volume": + "65", "pages": "1311-1311", "name": "Cancer Research"}, "authors": [{"authorId": + "152500082", "name": "M. Kharas"}, {"authorId": "34820441", "name": "T. Moore"}, + {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6241317", "name": "D. Fruman"}]}, {"paperId": + "5aca15f465d45cdddb35b7e30fbdfbcc0cec26f5", "externalIds": {"MAG": "2024406739", + "DOI": "10.1007/BF01868774", "CorpusId": 20664895, "PubMed": "6148424"}, "corpusId": + 20664895, "publicationVenue": {"id": "41cc63f8-c51d-469c-b169-65dfc2f9e2a6", + "name": "Journal of Membrane Biology", "type": "journal", "alternate_names": + ["The Journal of Membrane Biology", "J Membr Biology"], "issn": "0022-2631", + "url": "http://www.springer.com/life+sci/biochemistry+and+biophysics/journal/232", + "alternate_urls": ["https://link.springer.com/journal/232"]}, "url": "https://www.semanticscholar.org/paper/5aca15f465d45cdddb35b7e30fbdfbcc0cec26f5", + "title": "The plasma membrane (Mg2+)-dependent adenosine triphosphatase from + the human erythrocyte is not an ion pump", "abstract": null, "venue": "Journal + of Membrane Biology", "year": 2005, "referenceCount": 47, "citationCount": + 2, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": null, "journal": {"volume": "80", "pages": "185-190", + "name": "The Journal of Membrane Biology"}, "authors": [{"authorId": "145289081", + "name": "M. Forgac"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "608fbc091b340ae36c36eb4b2bb1ac1a41371679", "externalIds": {"MAG": "2324902959", + "DOI": "10.1016/S1040-1741(08)70159-3", "CorpusId": 23695860, "PubMed": "16106023"}, + "corpusId": 23695860, "publicationVenue": {"id": "917421ed-0c48-4dc3-897b-a8caae75761d", + "name": "Journal of the National Cancer Institute", "type": "journal", "alternate_names": + ["J National Cancer Inst"], "issn": "0027-8874", "url": "http://jnci.oupjournals.org/", + "alternate_urls": ["http://jnci.oxfordjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/608fbc091b340ae36c36eb4b2bb1ac1a41371679", + "title": "Differential effects of gefitinib and cetuximab on non-small-cell + lung cancers bearing epidermal growth factor receptor mutations.", "abstract": + null, "venue": "Journal of the National Cancer Institute", "year": 2005, "referenceCount": + 46, "citationCount": 230, "influentialCitationCount": 7, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "97 16", "pages": "\n 1185-94\n ", + "name": "Journal of the National Cancer Institute"}, "authors": [{"authorId": + "4944777", "name": "T. Mukohara"}, {"authorId": "6828387", "name": "J. Engelman"}, + {"authorId": "35398614", "name": "N. Hanna"}, {"authorId": "2127357", "name": + "B. Yeap"}, {"authorId": "2109836647", "name": "S. Kobayashi"}, {"authorId": + "3734755", "name": "N. Lindeman"}, {"authorId": "3698254", "name": "B. Halmos"}, + {"authorId": "6927277", "name": "J. Pearlberg"}, {"authorId": "46281629", + "name": "Z. Tsuchihashi"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5523919", "name": "D. Tenen"}, {"authorId": "115060139", "name": + "B. Johnson"}, {"authorId": "5984202", "name": "P. J\u00e4nne"}]}, {"paperId": + "621d225cef47a0dd24af2edeb93c602c7cc6a5b5", "externalIds": {"MAG": "2501352848", + "DOI": "10.1182/BLOOD.V106.11.732.732", "CorpusId": 89303813}, "corpusId": + 89303813, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/621d225cef47a0dd24af2edeb93c602c7cc6a5b5", + "title": "Phosphatidyl Inositol (4,5)P2 Marks Megakaryocyte Internal Membranes + and Is Associated with Megakaryocyte Maturation and Platelet Release.", "abstract": + "To produce blood platelets, the megakaryocyte (MK) cytoplasm elaborates proplatelets, + accompanied by expansion of membrane surface area and dramatic cytoskeletal + rearrangements. Invaginated demarcation membranes (DMS) are thought to be + the source for the proplatelet and platelet membranes, however, they have + THUS far BEEN INSUFFICIENTLY characterized. We first used a mouse model where + the cDNA encoding enhanced yellow fluorescence protein (EYFP) with a C-terminally + introduced myristoyl acceptor site has been introduced into the GPIIb locus. + Heterozygous knock-in mice reveal yellow fluroescent MKs with an internal + staining pattern that resembles the reticiulated pattern of the DMS as found + in micrographs. Proplatelet-forming MKs reveal contiguous membrane connection + between the internally stained membranes and the outlines of the proplatelet + shaft resulting in production of fluorescent platelets. We next sought to + characterize the internal membranes biochemically and retrovirally infected + MKs to express the green fluorescence protein (EGFP) tagged with the pleckstrin + homology domain of phospholipase C\u03b41 (PLC\u03b41) which binds with high + specificity to phosphatidylinositol(4,5)P2 (PIP2). Young MKs stain the cell + periphery as described for most other cell types. Mature MKs, however, stain + the internal membranes, whereas the plasma membrane becomes PIP2-negative + as shown by co-staining with CD41. Proplatelet membranes emanate from these + internal PIP2-positive membranes, proving that the DMS is indeed the membrane + reservoir during platelet biogenesis. Appearance of PI-4,5-P2 in the DMS occurs + in proximity to PI-5-P-4-kinase\u03b1 (PI4K\u03b1), a protein highly expressed + in MKs and platelets, as shown by overexpressing EGFP-tagged kinase in primary + MKs. In addition, shRNA-mediated loss of PIP4K\u03b1 or depletion of its presumptive + substrate block DMS development and expansion of MK size. Thus, PI-4,5-P2 + is a marker and essential component of internal membranes and is most likely + introduced about the non-canonical pathway using PI5P as the substrate. PI-4,5-P2 + promotes actin polymerization by activating small GTPases from the Rac/Rho + superfamily as well as Wiskott-Aldrich Syndrome (WASp) family proteins. Indeed, + PIP2 is associated with filamentous actin when MKs are co-stained with phalloidin. + Expression of a dominant-negative N-WASp C-terminal fragment (CA-domain) that + inactivats all WASp/WAVE family members leads to Arp3 binding without assembling + the complete Arp2/3 complex, thus inhibiting actin filament nucleation. F-Actin + staining in the infected MKs reveals a pattern similar to that of MKs treated + with pharmacologic dosage of actin polymerization-antagonists like cytochalasin + D, which disrupts actin filaments and inhibits proplatelet formation when + administered early in MK culture. Dominant-negative WASp impairs proplatelet + elaboration similarly, acting at a step past expansion of the cell volume. + These observations implicate a signaling pathway wherein PI-4,5-P2 facilitates + DMS development and suggests a pathway that links a DMS lipid marker with + local assembly of actin fibers as a requirement for platelet biogenesis.", + "venue": "", "year": 2005, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2005-11-16", "journal": {"volume": "106", "pages": "732-732", "name": "Blood"}, + "authors": [{"authorId": "145453589", "name": "H. Schulze"}, {"authorId": + "4263913", "name": "M. Korpal"}, {"authorId": "50139635", "name": "J. Hurov"}, + {"authorId": "2109704632", "name": "Sang-We Kim"}, {"authorId": "2108045556", + "name": "Jinghang Zhang"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "144437468", "name": "T. Graf"}, {"authorId": "2785025", "name": + "R. Shivdasani"}]}, {"paperId": "663e2ca43ad12040f62098e32073013c095d5223", + "externalIds": {"MAG": "2975564322", "DOI": "10.2210/pdb1yrk/pdb", "CorpusId": + 204105166}, "corpusId": 204105166, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/663e2ca43ad12040f62098e32073013c095d5223", + "title": "The C2 Domain of PKC is a new Phospho-Tyrosine Binding Domain", + "abstract": null, "venue": "", "year": 2005, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2005-07-26", "journal": {"volume": + "", "name": ""}, "authors": [{"authorId": "1714039", "name": "C. Benes"}, + {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": "35398419", "name": + "A. Elia"}, {"authorId": "32165121", "name": "T. Dharia"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4324390", "name": "S. Soltoff"}]}, {"paperId": + "6782f7973a81c1b9f97c84e384038aa6f3deec7e", "externalIds": {"MAG": "2133942178", + "DOI": "10.1101/GAD.1311105", "CorpusId": 1240553, "PubMed": "15985609"}, + "corpusId": 1240553, "publicationVenue": {"id": "94df828d-8411-48df-8aec-f13101ebb8f4", + "name": "Genes & Development", "type": "journal", "alternate_names": ["Gene Dev"], + "issn": "0890-9369", "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=101", + "alternate_urls": ["http://www.genesdev.org/", "http://genesdev.cshlp.org/"]}, + "url": "https://www.semanticscholar.org/paper/6782f7973a81c1b9f97c84e384038aa6f3deec7e", + "title": "The Mycobacterium tuberculosis serine/threonine kinases PknA and + PknB: substrate identification and regulation of cell shape.", "abstract": + "The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase + genes including two, pknA and pknB, that are part of an operon encoding genes + involved in cell shape control and cell wall synthesis. Here we demonstrate + that pknA and pknB are predominantly expressed during exponential growth, + and that overexpression of these kinases slows growth and alters cell morphology. + We determined the preferred substrate motifs of PknA and PknB, and identified + three in vivo substrates of these kinases: PknB; Wag31, an ortholog of the + cell division protein DivIVA; and Rv1422, a conserved protein of unknown function. + Expression of different alleles of wag31 in vivo alters cell shape, in a manner + dependent on the phosphoacceptor residue in the protein produced. Partial + depletion of pknA or pknB results in narrow, elongated cells. These data indicate + that signal transduction mediated by these kinases is a novel mechanism for + the regulation of cell shape in mycobacteria, one that may be conserved among + gram-positive bacteria.", "venue": "Genes & Development", "year": 2005, "referenceCount": + 38, "citationCount": 376, "influentialCitationCount": 43, "isOpenAccess": + true, "openAccessPdf": {"url": "http://genesdev.cshlp.org/content/19/14/1692.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2005-07-15", "journal": {"volume": + "19 14", "pages": "\n 1692-704\n ", "name": "Genes & development"}, + "authors": [{"authorId": "50717577", "name": "C. Kang"}, {"authorId": "145759174", + "name": "Derek W. Abbott"}, {"authorId": "30877912", "name": "S. T. Park"}, + {"authorId": "3748659", "name": "C. Dascher"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "3216305", "name": "R. Husson"}]}, {"paperId": + "6d09951c91bf36006dbac37de3c39a99355960be", "externalIds": {"MAG": "2099051331", + "DOI": "10.1074/jbc.M506967200", "CorpusId": 37538310, "PubMed": "16166093"}, + "corpusId": 37538310, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/6d09951c91bf36006dbac37de3c39a99355960be", + "title": "Increased P85\u03b1 Is a Potent Negative Regulator of Skeletal Muscle + Insulin Signaling and Induces in Vivo Insulin Resistance Associated with Growth + Hormone Excess*", "abstract": "Insulin resistance is a cardinal feature of + normal pregnancy and excess growth hormone (GH) states, but its underlying + mechanism remains enigmatic. We previously found a significant increase in + the p85 regulatory subunit of phosphatidylinositol kinase (PI 3-kinase) and + striking decrease in IRS-1-associated PI 3-kinase activity in the skeletal + muscle of transgenic animals overexpressing human placental growth hormone. + Herein, using transgenic mice bearing deletions in p85\u03b1, p85\u03b2, or + insulin-like growth factor-1, we provide novel evidence suggesting that overexpression + of p85\u03b1 is a primary mechanism for skeletal muscle insulin resistance + in response to GH. We found that the excess in total p85 was entirely accounted + for by an increase in the free p85\u03b1-specific isoform. In mice with a + liver-specific deletion in insulin-like growth factor-1, excess GH caused + insulin resistance and an increase in skeletal muscle p85\u03b1, which was + completely reversible using a GH-releasing hormone antagonist. To understand + the role of p85\u03b1 in GH-induced insulin resistance, we used mice bearing + deletions of the genes coding for p85\u03b1 or p85\u03b2, respectively (p85\u03b1 + +/\u2013 and p85\u03b2\u2013/\u2013). Wild type and p85\u03b2\u2013/\u2013 + mice developed in vivo insulin resistance and demonstrated overexpression + of p85\u03b1 and reduced insulin-stimulated PI 3-kinase activity in skeletal + muscle in response to GH. In contrast, p85\u03b1+/\u2013mice retained global + insulin sensitivity and PI 3-kinase activity associated with reduced p85\u03b1 + expression. These findings demonstrated the importance of increased p85\u03b1 + in mediating skeletal muscle insulin resistance in response to GH and suggested + a potential role for reducing p85\u03b1 as a therapeutic strategy for enhancing + insulin sensitivity in skeletal muscle.", "venue": "Journal of Biological + Chemistry", "year": 2005, "referenceCount": 19, "citationCount": 147, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925820592077/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2005-11-11", "journal": {"volume": "280", "pages": "37489 + - 37494", "name": "Journal of Biological Chemistry"}, "authors": [{"authorId": + "3688607", "name": "L. Barbour"}, {"authorId": "16357511", "name": "Shaikh + Mizanoor Rahman"}, {"authorId": "2085695734", "name": "I. Gurevich"}, {"authorId": + "1765665", "name": "J. Leitner"}, {"authorId": "40654003", "name": "S. Fischer"}, + {"authorId": "47109935", "name": "M. Roper"}, {"authorId": "32789701", "name": + "T. Knotts"}, {"authorId": "6739808", "name": "Y. Vo"}, {"authorId": "3651315", + "name": "C. McCurdy"}, {"authorId": "5698844", "name": "S. Yakar"}, {"authorId": + "4504946", "name": "D. Leroith"}, {"authorId": "144391716", "name": "C. Kahn"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1796879", "name": + "J. Friedman"}, {"authorId": "5662727", "name": "B. Draznin"}]}, {"paperId": + "6d0f2e2803c71b21cd435abb493a5ea97bac4ea9", "externalIds": {"MAG": "2077994677", + "DOI": "10.1074/jbc.M412065200", "CorpusId": 20738175, "PubMed": "15713674"}, + "corpusId": 20738175, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/6d0f2e2803c71b21cd435abb493a5ea97bac4ea9", + "title": "DNA Damage-induced Association of ATM with Its Target Proteins Requires + a Protein Interaction Domain in the N Terminus of ATM*", "abstract": "The + ATM protein kinase regulates the response of the cell to DNA damage by associating + with and then phosphorylating proteins involved in cell cycle checkpoints + and DNA repair. Here, we report on deletion studies designed to identify protein + domains required for ATM to phosphorylate target proteins and to control cell + survival following exposure to ionizing radiation. Deletion studies demonstrated + that amino acids 1\u2013150 of ATM were required for the ATM protein to regulate + cellular radiosensitivity. Additional deletions and point mutations indicated + that this domain extended from amino acids 81\u2013106 of ATM, with amino + acid substitutions located between amino acids 91 and 97 inactivating the + functional activity of ATM. When ATM with mutations in this region (termed + ATM90) was expressed in AT cells, it was unable to restore normal radiosensitivity + to the cells. However, ATM90 retained normal kinase activity and was autophosphorylated + on serine 1981 following exposure to DNA damage. Furthermore, wild-type ATM + displayed DNA-damage induced association with p53, brca1, and LKB1 in vivo, + whereas ATM90 failed to form productive complexes with these target proteins + either in vivo or in vitro. Furthermore, ATM90 did not phosphorylate p53 in + vivo and did not form nuclear foci in response to ionizing radiation. We propose + that amino acids 91\u201397 of ATM contain a protein interaction domain required + for the DNA damage-induced association between ATM and its target proteins, + including the brca1, p53, and LKB1 proteins. Furthermore, this domain of ATM + is required for ATM to form nuclear foci following exposure to ionizing radiation.", + "venue": "Journal of Biological Chemistry", "year": 2005, "referenceCount": + 36, "citationCount": 73, "influentialCitationCount": 4, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/280/15/15158.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2005-04-15", "journal": {"volume": + "280", "pages": "15158 - 15164", "name": "Journal of Biological Chemistry"}, + "authors": [{"authorId": "144613406", "name": "N. Fernandes"}, {"authorId": + "2837150", "name": "Yingli Sun"}, {"authorId": "2144303098", "name": "Shujuan + Chen"}, {"authorId": "2059688003", "name": "Proma Paul"}, {"authorId": "4426388", + "name": "R. Shaw"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1732453", "name": "B. Price"}]}, {"paperId": "719fb04fd061a2478522fe8233b6687052561d54", + "externalIds": {"MAG": "2001493878", "DOI": "10.1007/BF01871514", "CorpusId": + 1207676, "PubMed": "2993627"}, "corpusId": 1207676, "publicationVenue": {"id": + "41cc63f8-c51d-469c-b169-65dfc2f9e2a6", "name": "Journal of Membrane Biology", + "type": "journal", "alternate_names": ["The Journal of Membrane Biology", + "J Membr Biology"], "issn": "0022-2631", "url": "http://www.springer.com/life+sci/biochemistry+and+biophysics/journal/232", + "alternate_urls": ["https://link.springer.com/journal/232"]}, "url": "https://www.semanticscholar.org/paper/719fb04fd061a2478522fe8233b6687052561d54", + "title": "Delta endotoxin inhibits Rb+ uptake, lowers cytoplasmic pH and inhibits + a K+-ATPase inManduca sexta CHE cells", "abstract": null, "venue": "Journal + of Membrane Biology", "year": 2005, "referenceCount": 33, "citationCount": + 5, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "85", "pages": "199-204", "name": + "The Journal of Membrane Biology"}, "authors": [{"authorId": "34784769", "name": + "L. English"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "7513cfcaf72f455da866bbe522ef36b36eba6854", "externalIds": {"MAG": "1981682252", + "DOI": "10.1128/MCB.25.7.2593-2606.2005", "CorpusId": 25200624, "PubMed": + "15767666"}, "corpusId": 25200624, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/7513cfcaf72f455da866bbe522ef36b36eba6854", + "title": "Role of Phosphoinositide 3-Kinase Regulatory Isoforms in Development + and Actin Rearrangement", "abstract": "ABSTRACT Class Ia phosphoinositide + 3-kinases (PI3Ks) are heterodimers of p110 catalytic and p85 regulatory subunits + that mediate a variety of cellular responses to growth and differentiation + factors. Although embryonic development is not impaired in mice lacking all + isoforms of the p85\u03b1 gene (p85\u03b1\u2212/\u2212 p55\u03b1\u2212/\u2212 + p50\u03b1\u2212/\u2212) or in mice lacking the p85\u03b2 gene (p85\u03b2\u2212/\u2212) + (D. A. Fruman, F. Mauvais-Jarvis, D. A. Pollard, C. M. Yballe, D. Brazil, + R. T. Bronson, C. R. Kahn, and L. C. Cantley, Nat Genet. 26:379-382, 2000; + K. Ueki, C. M. Yballe, S. M. Brachmann, D. Vicent, J. M. Watt, C. R. Kahn, + and L. C. Cantley, Proc. Natl. Acad. Sci. USA 99:419-424, 2002), we show here + that loss of both genes results in lethality at embryonic day 12.5 (E12.5). + The phenotypes of these embryos, including subepidermal blebs flanking the + neural tube at E8 and bleeding into the blebs during the turning process, + are similar to defects observed in platelet-derived growth factor receptor + \u03b1 null (PDGFR\u03b1\u2212/\u2212) mice (P. Soriano, Development 124:2691-2700, + 1997), suggesting that PI3K is an essential mediator of PDGFR\u03b1 signaling + at this developmental stage. p85\u03b1\u2212/\u2212 p55\u03b1+/+ p50\u03b1+/+ + p85\u03b2\u2212/\u2212 mice had similar but less severe defects, indicating + that p85\u03b1 and p85\u03b2 have a critical and redundant function in development. + Mouse embryo fibroblasts deficient in all p85\u03b1 and p85\u03b2 gene products + (p85\u03b1\u2212/\u2212 p55\u03b1\u2212/\u2212 p50\u03b1\u2212/\u2212 p85\u03b2\u2212/\u2212) + are defective in PDGF-induced membrane ruffling. Overexpression of the Rac-specific + GDP-GTP exchange factor Vav2 or reintroduction of p85\u03b1 or p85\u03b2 rescues + the membrane ruffling defect. Surprisingly, reintroduction of p50\u03b1 also + restored PDGF-dependent membrane ruffling. These results indicate that class + Ia PI3K is critical for PDGF-dependent actin rearrangement but that the SH3 + domain and the Rho/Rac/Cdc42-interacting domain of p85, which lacks p50\u03b1, + are not required for this response.", "venue": "Molecular and Cellular Biology", + "year": 2005, "referenceCount": 55, "citationCount": 139, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1061637?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2005-04-01", "journal": {"volume": + "25", "pages": "2593 - 2606", "name": "Molecular and Cellular Biology"}, "authors": + [{"authorId": "3710358", "name": "S. Brachmann"}, {"authorId": "7777071", + "name": "C. Yballe"}, {"authorId": "47104808", "name": "M. Innocenti"}, {"authorId": + "33653557", "name": "Jonathan A. Deane"}, {"authorId": "6241317", "name": + "D. Fruman"}, {"authorId": "1909079", "name": "Sheila M. Thomas"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "7968640fd68df779469975a15661fbf9161b32c3", + "externalIds": {"MAG": "2168009839", "DOI": "10.1016/J.ADVENZREG.2005.02.010", + "CorpusId": 2061342, "PubMed": "16199078"}, "corpusId": 2061342, "publicationVenue": + {"id": "d04a7366-76cb-4b8a-b3ca-35b14bd12c87", "name": "Advances in Enzyme + Regulation", "type": "journal", "alternate_names": ["Adv Enzym Regul"], "issn": + "0065-2571", "alternate_issns": ["1873-2437"], "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/427/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00652571"]}, + "url": "https://www.semanticscholar.org/paper/7968640fd68df779469975a15661fbf9161b32c3", + "title": "Modification of protein sub-nuclear localization by synthetic phosphoinositides: + evidence for nuclear phosphoinositide signaling mechanisms.", "abstract": + null, "venue": "Advances in Enzyme Regulation", "year": 2005, "referenceCount": + 63, "citationCount": 13, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": null, "journal": + {"volume": "45", "pages": "\n 171-85\n ", "name": "Advances + in enzyme regulation"}, "authors": [{"authorId": "6896988", "name": "O. Gozani"}, + {"authorId": "123039768", "name": "S. Field"}, {"authorId": "143978896", "name": + "C. G. Ferguson"}, {"authorId": "4434881", "name": "M. Ewalt"}, {"authorId": + "8563805", "name": "Christian Mahlke"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "2565299", "name": "G. Prestwich"}, {"authorId": "40146895", + "name": "Junying Yuan"}]}, {"paperId": "862073eed118cddbcb5ca696c7320ea3591da4da", + "externalIds": {"CorpusId": 36332755, "PubMed": "16131837"}, "corpusId": 36332755, + "publicationVenue": {"id": "1bce1796-d800-4a09-91e5-d3e3ed025037", "name": + "Cell Cycle", "type": "journal", "issn": "1551-4005", "url": "http://www.landesbioscience.com/journals/cc/", + "alternate_urls": ["http://www.tandfonline.com/loi/kccy20"]}, "url": "https://www.semanticscholar.org/paper/862073eed118cddbcb5ca696c7320ea3591da4da", + "title": "The negative regulation of phosphoinositide 3-kinase signaling by + p85 and it''s implication in cancer.", "abstract": "The phosphoinositide 3-kinase + (PI3K) signaling pathway critically regulates cell growth and cell survival. + Mutations that lead to aberrant activation of this pathway are frequent events + in human cancers. Here we discuss some recent studies identifying the mechanisms + by which p85, the regulatory subunit of PI3K, negatively regulates PI3K signaling. + While necessary for the stability and membrane recruitment of the p110 catalytic + subunit of PI3K. p85 represses the basal activity of p110 in the absence of + growth factor stimulation. In its unbound, free form, p85 sequesters the adaptor + protein IRS-1 and therefore limits the extent of PI3K signaling downstream + of the insulin and IGF-1 receptors. These findings lend new insight to how + changes in p85 gene dosage or mutations in p85 could lead to the hyper-activation + of PI3K and thus contribute towards tumorigenesis.", "venue": "Cell Cycle", + "year": 2005, "referenceCount": 0, "citationCount": 76, "influentialCitationCount": + 3, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "4 10", "pages": "\n 1309-12\n ", + "name": "Cell cycle"}, "authors": [{"authorId": "145954100", "name": "Ji Luo"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "93028da3cd52ebc38cd2778ff6e04e34acad2478", + "externalIds": {"MAG": "2086524655", "DOI": "10.1101/GAD.1314605", "CorpusId": + 21627960, "PubMed": "16027169"}, "corpusId": 21627960, "publicationVenue": + {"id": "94df828d-8411-48df-8aec-f13101ebb8f4", "name": "Genes & Development", + "type": "journal", "alternate_names": ["Gene Dev"], "issn": "0890-9369", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=101", "alternate_urls": + ["http://www.genesdev.org/", "http://genesdev.cshlp.org/"]}, "url": "https://www.semanticscholar.org/paper/93028da3cd52ebc38cd2778ff6e04e34acad2478", + "title": "Feedback inhibition of Akt signaling limits the growth of tumors + lacking Tsc2.", "abstract": "The PTEN and TSC2 tumor suppressors inhibit mammalian + target of rapamycin (mTOR) signaling and are defective in distinct hamartoma + syndromes. Using mouse genetics, we find that Pten and Tsc2 act synergistically + to suppress the severity of a subset of tumors specific to loss of each of + these genes. Interestingly, we find that the slow-growing tumors specific + to Tsc2+/- mice exhibit defects in signaling downstream of Akt. However, Pten + haploinsufficiency restores Akt signaling in these tumors and dramatically + enhances their severity. This study demonstrates that attenuation of the PI3K-Akt + pathway in tumors lacking TSC2 contributes to their benign nature.", "venue": + "Genes & Development", "year": 2005, "referenceCount": 39, "citationCount": + 255, "influentialCitationCount": 13, "isOpenAccess": true, "openAccessPdf": + {"url": "http://genesdev.cshlp.org/content/19/15/1773.full.pdf", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2005-08-01", "journal": {"volume": "19 15", "pages": "\n 1773-8\n ", + "name": "Genes & development"}, "authors": [{"authorId": "2339651", "name": + "B. Manning"}, {"authorId": "143800250", "name": "M. Logsdon"}, {"authorId": + "5359676", "name": "A. Lipovsky"}, {"authorId": "145759174", "name": "Derek + W. Abbott"}, {"authorId": "2942901", "name": "D. Kwiatkowski"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "98b846347cb182403f0a29bf004a93dfcd14194d", + "externalIds": {"MAG": "2159370679", "DOI": "10.1016/j.cub.2005.06.059", "CorpusId": + 10494885, "PubMed": "16085494"}, "corpusId": 10494885, "publicationVenue": + {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", "name": "Current Biology", + "type": "journal", "alternate_names": ["Curr Biology"], "issn": "0960-9822", + "url": "http://www.current-biology.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/09609822"]}, + "url": "https://www.semanticscholar.org/paper/98b846347cb182403f0a29bf004a93dfcd14194d", + "title": "PtdIns(4,5)P2 Functions at the Cleavage Furrow during Cytokinesis", + "abstract": null, "venue": "Current Biology", "year": 2005, "referenceCount": + 28, "citationCount": 186, "influentialCitationCount": 19, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S0960982205007074/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "2005-08-09", "journal": {"volume": + "15", "pages": "1407-1412", "name": "Current Biology"}, "authors": [{"authorId": + "123039768", "name": "S. Field"}, {"authorId": "6347712", "name": "Nikki Madson"}, + {"authorId": "5196339", "name": "M. L. Kerr"}, {"authorId": "2058329252", + "name": "K. Galbraith"}, {"authorId": "144705393", "name": "Caitlin Kennedy"}, + {"authorId": "5749666", "name": "M. Tahiliani"}, {"authorId": "3679332", "name": + "A. Wilkins"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "a8a68e5fe39a390b06ed54a1adeb9970b25b4545", "externalIds": {"MAG": "2043052104", + "DOI": "10.1073/PNAS.0503141102", "CorpusId": 8342266, "PubMed": "15928075"}, + "corpusId": 8342266, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/a8a68e5fe39a390b06ed54a1adeb9970b25b4545", + "title": "Building a human kinase gene repository: bioinformatics, molecular + cloning, and functional validation.", "abstract": "Kinases catalyze the phosphorylation + of proteins, lipids, sugars, nucleosides, and other important cellular metabolites + and play key regulatory roles in all aspects of eukaryotic cell physiology. + Here, we describe the mining of public databases to collect the sequence information + of all identified human kinase genes and the cloning of the corresponding + ORFs. We identified 663 genes, 511 encoding protein kinases, and 152 encoding + nonprotein kinases. We describe the successful cloning and sequence verification + of 270 of these genes. Subcloning of this gene set in mammalian expression + vectors and their use in high-throughput cell-based screens allowed the validation + of the clones at the level of expression and the identification of previously + uncharacterized modulators of the survivin promoter. Moreover, expressions + of the kinase genes in bacteria, followed by autophosphorylation assays, identified + 21 protein kinases that showed autocatalytic activity. The work described + here will facilitate the functional assaying of this important gene family + in phenotypic screens and their use in biochemical and structural studies.", + "venue": "Proceedings of the National Academy of Sciences of the United States + of America", "year": 2005, "referenceCount": 46, "citationCount": 39, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1149441?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2005-06-07", "journal": {"volume": + "102 23", "pages": "\n 8114-9\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "2116811142", "name": "Jaehong Park"}, {"authorId": "2228212", + "name": "Yanhui Hu"}, {"authorId": "37452956", "name": "T. Murthy"}, {"authorId": + "2729254", "name": "F. Vannberg"}, {"authorId": "144531145", "name": "Binghua + Shen"}, {"authorId": "35454156", "name": "A. Rolfs"}, {"authorId": "6742227", + "name": "Jessica E. Hutti"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2112063", "name": "J. LaBaer"}, {"authorId": "143686358", "name": + "E. Harlow"}, {"authorId": "144818828", "name": "L. Brizuela"}]}, {"paperId": + "b3080d83a570d1341899e3cbc6e535ff234e8425", "externalIds": {"MAG": "2159791953", + "DOI": "10.1073/PNAS.0504378102", "CorpusId": 26909029, "PubMed": "16006513"}, + "corpusId": 26909029, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/b3080d83a570d1341899e3cbc6e535ff234e8425", + "title": "Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- + mice by the p85 regulatory subunits of phosphoinositide 3-kinase.", "abstract": + "Mice with heterozygous deletion of the PTEN tumor suppressor gene develop + a range of epithelial neoplasia as well as lymphoid hyperplasia. Previous + studies suggest that PTEN suppresses tumor formation by acting as a phosphoinositide + phosphatase to limit signaling by phosphoinositide 3-kinase (PI3K). Here, + we examined the effect of deleting various regulatory subunits of PI3K (p85alpha + and p85beta) on epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice. + Interestingly, we found the loss of one p85alpha allele with or without the + loss of p85beta led to increased incidence of intestinal polyps. Signaling + downstream of PI3K was enhanced in the PTEN+/-p85alpha+/-p85beta-/- polyps, + as judged by an increased fraction of both cells with cytoplasmic staining + of the transcription factor FKHR and cells with positive staining for the + proliferation marker Ki-67. In contrast, the incidence of prostate intraepithelial + neoplasia was not significantly altered in PTEN+/- mice heterozygous for p85alpha + or null for p85beta, whereas the fraction of proliferating cells in prostate + intraepithelial neoplasia was reduced in mice lacking p85beta. Finally, there + was no significant change in T lymphocyte hyperplasia in the PTEN+/- mice + with various p85 deletions, although anti-CD3-stimulated AKT activation was + somewhat reduced in the p85alpha+/- background. These results indicate that + decreasing the levels of different p85 regulatory subunits can result in enhanced + PI3K signaling in some tissues and decreased PI3K signaling in others, supporting + the model that, although p85 proteins are essential for class I(A) PI3K signaling, + they can function as inhibitors of PI3K signaling in some tissues and thus + suppress tumor formation.", "venue": "Proceedings of the National Academy + of Sciences of the United States of America", "year": 2005, "referenceCount": + 32, "citationCount": 50, "influentialCitationCount": 2, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1174923?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "2005-07-19", "journal": {"volume": "102 29", + "pages": "\n 10238-43\n ", "name": "Proceedings of the National + Academy of Sciences of the United States of America"}, "authors": [{"authorId": + "145954100", "name": "Ji Luo"}, {"authorId": "16248879", "name": "Cassandra + L Sobkiw"}, {"authorId": "11269726", "name": "Nicole M Logsdon"}, {"authorId": + "40474206", "name": "J. Watt"}, {"authorId": "7505152", "name": "S. Signoretti"}, + {"authorId": "1398422569", "name": "F. O''connell"}, {"authorId": "40536567", + "name": "Eyoung Shin"}, {"authorId": "82732598", "name": "Youn-Soo Shim"}, + {"authorId": "5471449", "name": "L. Pao"}, {"authorId": "2291271", "name": + "B. Neel"}, {"authorId": "5593407", "name": "R. DePinho"}, {"authorId": "6213932", + "name": "M. Loda"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "c533dfdd9f821cecb709589ae34b971e2ea3a795", "externalIds": {"MAG": "2048818391", + "DOI": "10.1016/S0169-5002(05)80141-2", "CorpusId": 72318826}, "corpusId": + 72318826, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/c533dfdd9f821cecb709589ae34b971e2ea3a795", + "title": "O-009 Differential effects of gefitinib and cetuximab on EGFR mutant + non-small cell lung cancers (NSCLC) cell lines", "abstract": null, "venue": + "", "year": 2005, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2005-07-01", "journal": null, "authors": [{"authorId": "4944777", "name": + "T. Mukohara"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": + "3734755", "name": "N. Lindeman"}, {"authorId": "6927277", "name": "J. Pearlberg"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "115060139", "name": + "B. Johnson"}, {"authorId": "5984202", "name": "P. J\u00e4nne"}]}, {"paperId": + "cb2ab298e9b0c358db9700532a8478ba457642ff", "externalIds": {"MAG": "2119863908", + "DOI": "10.1021/BC049714F", "CorpusId": 1783990, "PubMed": "15898736"}, "corpusId": + 1783990, "publicationVenue": {"id": "727c9075-57df-4276-83b3-a90e2722f883", + "name": "Bioconjugate chemistry", "type": "journal", "alternate_names": ["Bioconjugate + Chem", "Bioconjugate chem", "Bioconjugate Chemistry"], "issn": "1043-1802", + "url": "https://pubs.acs.org/journal/bcches", "alternate_urls": ["http://pubs.acs.org/journals/bcches/index.html", + "http://pubs.acs.org/journal/bcches"]}, "url": "https://www.semanticscholar.org/paper/cb2ab298e9b0c358db9700532a8478ba457642ff", + "title": "Synthesis and activity of C11-modified wortmannin probes for PI3 + kinase.", "abstract": "The key role played by PI3 kinase in cancer, hormone + action, and a host of other biological functions suggests that specific inhibitors + whose disposition could be ascertained in vivo would be useful in biological + research or, potentially, for imaging PI3K in a clinical setting. Wortmannin + (Wm, 1) is an inhibitor of PI3 kinase with high specificity for this enzyme. + We synthesized three modified Wm probes, a biotinylated Wm (7a), a 4-hydroxy-3-iodophenylated + Wm, which was obtained both unlabeled (7b) and labeled with (125)I (8), and + a fluoresceinated Wm (7c), through modification at C-11, and evaluated their + inhibitive activity as inhibitors of PI3 kinase. Biotinylated (7a) and 4-hydroxy-3-iodophenylated + Wm''s (7b) had IC(50)s for PI3K of 6.11 and 11.02 nM, respectively, compared + to an IC(50) for Wm of 1.63 nM. Fluoresceinated Wm (7c) lost considerably + more activity than the other derivatives, with an IC(50) of 64.9 nM. The (125)I + labeled 4-hydroxy-3-iodophenylated Wm (8) could be detected after reaction + with an immunoprecipitate of PI3 kinase. The activity of these reporter Wm''s + is discussed in relationship to earlier findings on the pharmacological activity + of Wm derivatives and the ability of inhibitors to fit into the ATP pocket + of PI3 kinase.", "venue": "Bioconjugate chemistry", "year": 2005, "referenceCount": + 19, "citationCount": 17, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2005-04-29", "journal": {"volume": + "16 3", "pages": "\n 669-75\n ", "name": "Bioconjugate chemistry"}, + "authors": [{"authorId": "6230104", "name": "Hushan Yuan"}, {"authorId": "145954100", + "name": "Ji Luo"}, {"authorId": "123039768", "name": "S. Field"}, {"authorId": + "3127756", "name": "R. Weissleder"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5095505", "name": "L. Josephson"}]}, {"paperId": "cf92b90535764070c4995b3f9a3d3780c80e2eaf", + "externalIds": {"MAG": "2137618229", "DOI": "10.1128/MCB.25.5.1596-1607.2005", + "CorpusId": 25212900, "PubMed": "15713620"}, "corpusId": 25212900, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/cf92b90535764070c4995b3f9a3d3780c80e2eaf", + "title": "Phosphoinositide 3-Kinase Catalytic Subunit Deletion and Regulatory + Subunit Deletion Have Opposite Effects on Insulin Sensitivity in Mice", "abstract": + "ABSTRACT Studies ex vivo have shown that phosphoinositide 3-kinase (PI3K) + activity is necessary but not sufficient for insulin-stimulated glucose uptake. + Unexpectedly, mice lacking either of the PI3K regulatory subunits p85\u03b1 + or p85\u03b2 exhibit increased insulin sensitivity. The insulin hypersensitivity + is particularly unexpected in p85\u03b1\u2212/\u2212 p55\u03b1\u2212/\u2212 + p50\u03b1\u2212/\u2212 mice, where a decrease in p110\u03b1 and p110\u03b2 + catalytic subunits was observed in insulin-sensitive tissues. These results + raised the possibility that decreasing total PI3K available for stimulation + by insulin might circumvent negative feedback loops that ultimately shut off + insulin-dependent glucose uptake in vivo. Here we present results arguing + against this explanation. We show that p110\u03b1+/\u2212 p110\u03b2+/\u2212 + mice exhibit mild glucose intolerance and hyperinsulinemia in the fasted state. + Unexpectedly, p110\u03b1+/\u2212 p110\u03b2+/\u2212 mice showed a \u223c50% + decrease in p85 expression in liver and muscle. Consistent with this in vivo + observation, knockdown of p110 by RNA interference in mammalian cells resulted + in loss of p85 proteins due to decreased protein stability. We propose that + insulin sensitivity is regulated by a delicate balance between p85 and p110 + subunits and that p85 subunits mediate a negative role in insulin signaling + independent of their role as mediators of PI3K activation.", "venue": "Molecular + and Cellular Biology", "year": 2005, "referenceCount": 51, "citationCount": + 183, "influentialCitationCount": 11, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc549361?pdf=render", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2005-03-01", "journal": {"volume": "25", "pages": "1596 + - 1607", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "3710358", "name": "S. Brachmann"}, {"authorId": "5177377", "name": "K. Ueki"}, + {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "2057941343", + "name": "R. Kahn"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "db3e6b920cc69825a0b289ec818443012ba49c1a", "externalIds": {"MAG": "2093087608", + "DOI": "10.1016/j.cell.2005.02.019", "CorpusId": 1498824}, "corpusId": 1498824, + "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": + "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": "0092-8674", + "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/00928674", "http://www.cell.com/", + "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/db3e6b920cc69825a0b289ec818443012ba49c1a", + "title": "The C2 Domain of PKC\u03b4 Is a Phosphotyrosine Binding Domain", + "abstract": null, "venue": "Cell", "year": 2005, "referenceCount": 64, "citationCount": + 210, "influentialCitationCount": 7, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867405001649/pdf", "status": null}, + "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2005-04-22", "journal": {"volume": + "121", "pages": "271-280", "name": "Cell"}, "authors": [{"authorId": "1714039", + "name": "C. Benes"}, {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": + "35398419", "name": "A. Elia"}, {"authorId": "32165121", "name": "T. Dharia"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4324390", "name": + "S. Soltoff"}]}, {"paperId": "e619703a3dc10b14e35775e1702e48910e73c92b", "externalIds": + {"MAG": "2042103473", "DOI": "10.1073/PNAS.0409773102", "CorpusId": 25837815, + "PubMed": "15731348"}, "corpusId": 25837815, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/e619703a3dc10b14e35775e1702e48910e73c92b", + "title": "ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive + non-small cell lung cancer cell lines.", "abstract": "Therapies that target + the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset + of patients with advanced non-small cell lung cancer (NSCLC). The differences + in intracellular signaling networks between gefitinib-sensitive and -resistant + NSCLCs remain poorly understood. In this study, we observe that gefitinib + reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. + To elucidate the mechanism underlying this observation, we compared immunoprecipitates + of phosphoinositide 3-kinase (PI3K) between gefitinib-sensitive and -resistant + NSCLC cell lines. We observe that PI3K associates with ErbB-3 exclusively + in gefitinib-sensitive NSCLC cell lines. Gefitinib dissociates this complex, + thereby linking EGFR inhibition to decreased Akt activity. In contrast, gefitinib-resistant + cells do not use ErbB-3 to activate the PI3K/Akt pathway. In fact, abundant + ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. + Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating + EGFR mutations (L858R and Del747-749), frequently observed in NSCLC patients + who respond to gefitinib, also use ErbB-3 to couple to PI3K. Down-regulation + of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels + in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT EGFR) and H3255 (L858R + EGFR), but has no effect on Akt activation in the gefitinib-resistant cell + lines, A549 and H522. We conclude that ErbB-3 is used to couple EGFR to the + PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and + mutant EGFRs.", "venue": "Proceedings of the National Academy of Sciences + of the United States of America", "year": 2005, "referenceCount": 29, "citationCount": + 527, "influentialCitationCount": 26, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.pnas.org/content/102/10/3788.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2005-03-08", "journal": {"volume": "102 10", "pages": "\n 3788-93\n ", + "name": "Proceedings of the National Academy of Sciences of the United States + of America"}, "authors": [{"authorId": "6828387", "name": "J. Engelman"}, + {"authorId": "5984202", "name": "P. J\u00e4nne"}, {"authorId": "145234673", + "name": "C. Mermel"}, {"authorId": "6927277", "name": "J. Pearlberg"}, {"authorId": + "4944777", "name": "T. Mukohara"}, {"authorId": "39554977", "name": "C. Fleet"}, + {"authorId": "6306836", "name": "K. Cichowski"}, {"authorId": "115060139", + "name": "B. Johnson"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "e8dbfd9f625841a52c4e3714b1a577c2b16c94da", "externalIds": {"MAG": "2010238890", + "DOI": "10.1126/science.1120781", "CorpusId": 206508115, "PubMed": "16308421"}, + "corpusId": 206508115, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/e8dbfd9f625841a52c4e3714b1a577c2b16c94da", + "title": "The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic + Effects of Metformin", "abstract": "The Peutz-Jegher syndrome tumor-suppressor + gene encodes a protein-threonine kinase, LKB1, which phosphorylates and activates + AMPK [adenosine monophosphate (AMP)\u2013activated protein kinase]. The deletion + of LKB1 in the liver of adult mice resulted in a nearly complete loss of AMPK + activity. Loss of LKB1 function resulted in hyperglycemia with increased gluconeogenic + and lipogenic gene expression. In LKB1-deficient livers, TORC2, a transcriptional + coactivator of CREB (cAMP response element\u2013binding protein), was dephosphorylated + and entered the nucleus, driving the expression of peroxisome proliferator-activated + receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1), which in turn drives gluconeogenesis. + Adenoviral small hairpin RNA (shRNA) for TORC2 reduced PGC-1\u03b1 expression + and normalized blood glucose levels in mice with deleted liver LKB1, indicating + that TORC2 is a critical target of LKB1/AMPK signals in the regulation of + gluconeogenesis. Finally, we show that metformin, one of the most widely prescribed + type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose + levels.", "venue": "Science", "year": 2005, "referenceCount": 49, "citationCount": + 1884, "influentialCitationCount": 133, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc3074427?pdf=render", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2005-12-09", "journal": {"volume": "310", "pages": "1642 - 1646", "name": + "Science"}, "authors": [{"authorId": "4426388", "name": "R. Shaw"}, {"authorId": + "5493258", "name": "K. Lamia"}, {"authorId": "49440900", "name": "Debbie S. + Vasquez"}, {"authorId": "1885308", "name": "S. Koo"}, {"authorId": "5974412", + "name": "N. Bardeesy"}, {"authorId": "5593407", "name": "R. DePinho"}, {"authorId": + "4892627", "name": "M. Montminy"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "ecef9a65d07cd8d9a8fed92c28e240ef183d4d8f", "externalIds": {"MAG": + "2043160859", "DOI": "10.1074/JBC.M504699200", "CorpusId": 2149884, "PubMed": + "15987685"}, "corpusId": 2149884, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/ecef9a65d07cd8d9a8fed92c28e240ef183d4d8f", + "title": "Diverse Biochemical Properties of Shp2 Mutants", "abstract": "Mutations + in the Src homology 2 (SH2)-containing protein-tyrosine phosphatase Shp2 (PTPN11) + underlie half of the cases of the autosomal dominant genetic disorder Noonan + syndrome, and somatic Shp2 mutations are found in several hematologic and + solid malignancies. Earlier studies of small numbers of mutants suggested + that disease-associated mutations cause constitutive (SH2 binding-independent) + activation and that cancer-associated mutants are more active than those associated + with Noonan syndrome. We have characterized a larger panel of Shp2 mutants + and find that this \u201cactivity-centric\u201d model cannot explain the behaviors + of all pathogenic Shp2 mutations. Instead, enzymatic, structural, and mathematical + modeling analyses show that these mutants can affect basal activation, SH2 + domain-phosphopeptide affinity, and/or substrate specificity to varying degrees. + Furthermore, there is no absolute correlation between the mutants'' extents + of basal activation and the diseases they induce. We propose that activated + mutants of Shp2 modulate signaling from specific stimuli to a subset of effectors + and provide a theoretical framework for understanding the complex relationship + between Shp2 activation, intracellular signaling, and pathology.", "venue": + "Journal of Biological Chemistry", "year": 2005, "referenceCount": 50, "citationCount": + 267, "influentialCitationCount": 16, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/280/35/30984.full.pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2005-09-02", "journal": {"volume": "280", "pages": "30984 + - 30993", "name": "Journal of Biological Chemistry"}, "authors": [{"authorId": + "6860109", "name": "H. Keilhack"}, {"authorId": "47687902", "name": "F. S. + David"}, {"authorId": "34824608", "name": "M. McGregor"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "2291271", "name": "B. Neel"}]}, {"paperId": + "ed730103730cfdeda1e50c3b3a209bc61e47be6c", "externalIds": {"MAG": "2099019742", + "DOI": "10.1158/0008-5472.CAN-05-2612", "CorpusId": 6121082, "PubMed": "16322248"}, + "corpusId": 6121082, "publicationVenue": {"id": "b0bd78b2-6591-460e-af71-196409b62e2c", + "name": "Cancer Research", "type": "journal", "alternate_names": ["Cancer + Res"], "issn": "0008-5472", "url": "https://cancerres.aacrjournals.org/", + "alternate_urls": ["http://cancerres.aacrjournals.org/"]}, "url": "https://www.semanticscholar.org/paper/ed730103730cfdeda1e50c3b3a209bc61e47be6c", + "title": "Breast cancer-associated PIK3CA mutations are oncogenic in mammary + epithelial cells.", "abstract": "Activation of the phosphoinositide 3-kinase + (PI3K) pathway has been implicated in the pathogenesis of a variety of cancers. + Recently, mutations in the gene encoding the p110alpha catalytic subunit of + PI3K (PIK3CA) have been identified in several human cancers. The mutations + primarily result in single amino acid substitutions, with >85% of the mutations + in either exon 9 or 20. Multiple studies have shown that these mutations are + observed in 18% to 40% of breast cancers. However, the phenotypic effects + of these PIK3CA mutations have not been examined in breast epithelial cells. + Herein, we examine the activity of the two most common variants, E545K and + H1047R, in the MCF-10A immortalized breast epithelial cell line. Both variants + display higher PI3K activity than wild-type p110alpha yet remain sensitive + to pharmacologic PI3K inhibition. In addition, expression of p110alpha mutants + in mammary epithelial cells induces multiple phenotypic alterations characteristic + of breast tumor cells, including anchorage-independent proliferation in soft + agar, growth factor-independent proliferation, and protection from anoikis. + Expression of these mutant p110alpha isoforms also confers increased resistance + to paclitaxel and induces abnormal mammary acinar morphogenesis in three-dimensional + basement membrane cultures. Together, these data support the notion that the + cancer-associated mutations in PIK3CA may significantly contribute to breast + cancer pathogenesis and represent attractive targets for therapeutic inhibition.", + "venue": "Cancer Research", "year": 2005, "referenceCount": 60, "citationCount": + 490, "influentialCitationCount": 19, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2005-12-01", "journal": {"volume": "65 23", "pages": "\n 10992-1000\n ", + "name": "Cancer research"}, "authors": [{"authorId": "4327978", "name": "S. + Isakoff"}, {"authorId": "6828387", "name": "J. Engelman"}, {"authorId": "49807003", + "name": "H. Irie"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "3710358", "name": "S. Brachmann"}, {"authorId": "3679091", "name": "R. Pearline"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3471778", "name": + "J. Brugge"}]}, {"paperId": "faabc285120865e63fbbf4170473b0775b935466", "externalIds": + {"CorpusId": 9911809, "PubMed": "15851033"}, "corpusId": 9911809, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/faabc285120865e63fbbf4170473b0775b935466", + "title": "The C2 domain of PKCdelta is a phosphotyrosine binding domain.", + "abstract": "In eukaryotic cells, the SH2 and PTB domains mediate protein-protein + interactions by recognizing phosphotyrosine residues on target proteins. Here + we make the unexpected finding that the C2 domain of PKCdelta directly binds + to phosphotyrosine peptides in a sequence-specific manner. We provide evidence + that this domain mediates PKCdelta interaction with a Src binding glycoprotein, + CDCP1. The crystal structure of the PKCdelta C2 domain in complex with an + optimal phosphopeptide reveals a new mode of phosphotyrosine binding in which + the phosphotyrosine moiety forms a ring-stacking interaction with a histidine + residue of the C2 domain. This is also the first example of a protein Ser/Thr + kinase containing a domain that binds phosphotyrosine.", "venue": "Cell", + "year": 2005, "referenceCount": 0, "citationCount": 133, "influentialCitationCount": + 7, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "121 2", "pages": "\n 271-80\n ", + "name": "Cell"}, "authors": [{"authorId": "1714039", "name": "C. Benes"}, + {"authorId": "2068343858", "name": "Ning Wu"}, {"authorId": "35398419", "name": + "A. Elia"}, {"authorId": "32165121", "name": "T. Dharia"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4324390", "name": "S. Soltoff"}]}, {"paperId": + "00a1a1d8057e3e88ea2eef8c8629d15a6b3a4f54", "externalIds": {"MAG": "2107565679", + "DOI": "10.1038/nsmb711", "CorpusId": 10346516, "PubMed": "14718925"}, "corpusId": + 10346516, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/00a1a1d8057e3e88ea2eef8c8629d15a6b3a4f54", + "title": "Identification of small molecule inhibitors of anthrax lethal factor", + "abstract": null, "venue": "Nature Structural &Molecular Biology", "year": + 2004, "referenceCount": 27, "citationCount": 134, "influentialCitationCount": + 2, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": null, "journal": {"volume": "11", "pages": + "67-72", "name": "Nature Structural &Molecular Biology"}, "authors": [{"authorId": + "144309531", "name": "R. Panchal"}, {"authorId": "9879291", "name": "A. Hermone"}, + {"authorId": "16060345", "name": "T. Nguyen"}, {"authorId": "50350421", "name": + "T. Y. Wong"}, {"authorId": "4049676", "name": "R. Schwarzenbacher"}, {"authorId": + "2150555618", "name": "J. Schmidt"}, {"authorId": "37878348", "name": "D. + Lane"}, {"authorId": "37255445", "name": "C. McGrath"}, {"authorId": "25581223", + "name": "B. Turk"}, {"authorId": "144328994", "name": "J. Burnett"}, {"authorId": + "145194566", "name": "M. Aman"}, {"authorId": "36135955", "name": "S. Little"}, + {"authorId": "3484009", "name": "E. Sausville"}, {"authorId": "3336343", "name": + "D. Zaharevitz"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4427762", "name": "R. Liddington"}, {"authorId": "2471354", "name": "R. Gussio"}, + {"authorId": "2539908", "name": "S. Bavari"}]}, {"paperId": "04b0c4339e6e58e9360995bf0afc246fee73a57a", + "externalIds": {"MAG": "2149312498", "DOI": "10.1074/JBC.M309721200", "CorpusId": + 26046836, "PubMed": "14701839"}, "corpusId": 26046836, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/04b0c4339e6e58e9360995bf0afc246fee73a57a", + "title": "Identification and Characterization of a Phosphoinositide Phosphate + Kinase Homolog*", "abstract": "Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) + plays a central role in regulating the actin cytoskeleton as a substrate for + phosphoinositide 3-kinase and phospholipase C as well as by binding directly + to proteins that control the processes of actin monomer sequestration, filament + severing, capping, nucleation, cross-linking, and bundling (Ma, L., Cantley, + L. C., Janmey, P. A., and Kirschner, M. W. (1998) J. Cell Biol. 140, 1125\u20131136; + Hinchliffe, K. (2000) Curr. Biol. 10, R104\u2013R1051). Three related phosphatidylinositol + 4-phosphate 5-kinases (PI(4)P 5-kinases) have been identified in mammalian + cells (types I\u03b1, I\u03b2, and I\u03b3) and appear to play distinct roles + in actin remodeling. Here we have identified a fourth member of this family + by searching the human genome and EST data bases. This new protein, which + we have designated phosphatidylinositol phosphate kinase homolog (PIPKH), + is expressed at relatively high levels in brain and testis. Immunoprecipitates + of PIPKH expressed in mammalian cells contain PI(4)P 5-kinase activity, but + this activity is not affected by mutations in residues that inactivate other + type I PI(4)P 5-kinases. We show that the PI(4)P 5-kinase activity in PIPKH + immunoprecipitates can be explained by the ability of PIPKH to heterodimerize + with other type I PI(4)P 5-kinases. Transfection of 293t cells with PIPKH + resulted in >8-fold increase in total phosphatidylinositol 3,4,5-trisphosphate + (PI(3,4,5)P3) without a significant net increase in total PI(4,5)P2. When + coexpressed with PIPKH, green fluorescent protein (GFP) fusion construct of + the pleckstrin homology domain from Bruton''s tyrosine kinase (GFP-BTK-PH) + localized in intracellular vesicular structures, suggesting an unusual intracellular + site of PI(3,4,5)P3 production. Finally, expression of PIPKH induced the reorganization + of actin from predominantly stress fibers to predominantly foci and comets + similar to those observed previously in cells infected with the intracellular + pathogen Listeria or transfected with recombinant PIPKI\u03b1. These results + suggest that PIPKH acts as a scaffold to localize and regulate type I PI(4)P + 5-kinases and the synthesis of PI(3,4,5)P3.", "venue": "Journal of Biological + Chemistry", "year": 2004, "referenceCount": 32, "citationCount": 20, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/279/12/11672.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2004-03-19", "journal": {"volume": + "279", "pages": "11672 - 11679", "name": "Journal of Biological Chemistry"}, + "authors": [{"authorId": "2116093125", "name": "James D. Chang"}, {"authorId": + "123039768", "name": "S. Field"}, {"authorId": "4109960", "name": "L. Rameh"}, + {"authorId": "2972505", "name": "C. Carpenter"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "31cdff697f23ed127b41226eecd00430839dbca0", "externalIds": + {"MAG": "2055854788", "DOI": "10.1038/431128a", "CorpusId": 85197250}, "corpusId": + 85197250, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/31cdff697f23ed127b41226eecd00430839dbca0", + "title": "Sizing up a growing field", "abstract": null, "venue": "Nature", + "year": 2004, "referenceCount": 0, "citationCount": 2, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.nature.com/articles/431128a.pdf", + "status": null}, "fieldsOfStudy": ["Environmental Science"], "s2FieldsOfStudy": + [{"category": "Environmental Science", "source": "external"}, {"category": + "Psychology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2004-09-01", "journal": {"volume": "431", "pages": "128-129", "name": "Nature"}, + "authors": [{"authorId": "2339651", "name": "B. Manning"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "47310b92c485a301788a19efd3b798ac84e8ad3c", + "externalIds": {"MAG": "1978479807", "DOI": "10.1016/J.YEXCR.2004.03.024", + "CorpusId": 6403470, "PubMed": "15194438"}, "corpusId": 6403470, "publicationVenue": + {"id": "e4d93d07-bb1f-45a0-bb72-c46ea127fc8c", "name": "Experimental Cell + Research", "type": "journal", "alternate_names": ["Exp Cell Res"], "issn": + "0014-4827", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/622826/description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00144827"]}, + "url": "https://www.semanticscholar.org/paper/47310b92c485a301788a19efd3b798ac84e8ad3c", + "title": "Differential regulation of the phosphoinositide 3-kinase and MAP + kinase pathways by hepatocyte growth factor vs. insulin-like growth factor-I + in myogenic cells.", "abstract": null, "venue": "Experimental Cell Research", + "year": 2004, "referenceCount": 57, "citationCount": 73, "influentialCitationCount": + 6, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], "publicationDate": + "2004-07-01", "journal": {"volume": "297 1", "pages": "\n 224-34\n ", + "name": "Experimental cell research"}, "authors": [{"authorId": "5224577", + "name": "O. Halevy"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "4d8d80589eface13e6884a88ea5f78515c2a9f67", "externalIds": {"MAG": "2006695188", + "DOI": "10.1038/nsmb708", "CorpusId": 39119275, "PubMed": "14718924"}, "corpusId": + 39119275, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4d8d80589eface13e6884a88ea5f78515c2a9f67", + "title": "The structural basis for substrate and inhibitor selectivity of + the anthrax lethal factor", "abstract": null, "venue": "Nature Structural + &Molecular Biology", "year": 2004, "referenceCount": 45, "citationCount": + 182, "influentialCitationCount": 8, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "11", "pages": "60-66", "name": "Nature Structural + &Molecular Biology"}, "authors": [{"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "50350421", "name": "T. Y. Wong"}, {"authorId": "4049676", "name": + "R. Schwarzenbacher"}, {"authorId": "7844726", "name": "E. Jarrell"}, {"authorId": + "145102855", "name": "S. Leppla"}, {"authorId": "2166180", "name": "R. Collier"}, + {"authorId": "4427762", "name": "R. Liddington"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "53b622ec0af40460fa81a5108dfc38b7eb35b444", + "externalIds": {"MAG": "2096244860", "DOI": "10.1074/jbc.M405842200", "CorpusId": + 5936098, "PubMed": "15199048"}, "corpusId": 5936098, "publicationVenue": {"id": + "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological Chemistry", + "type": "journal", "alternate_names": ["J Biological Chem"], "issn": "0021-9258", + "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", "alternate_urls": + ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": "https://www.semanticscholar.org/paper/53b622ec0af40460fa81a5108dfc38b7eb35b444", + "title": "A Multi-enzyme Cascade of Hemoglobin Proteolysis in the Intestine + of Blood-feeding Hookworms*", "abstract": "Blood-feeding pathogens digest + hemoglobin (Hb) as a source of nutrition, but little is known about this process + in multicellular parasites. The intestinal brush border membrane of the canine + hookworm, Ancylostoma caninum, contains aspartic proteases (APR-1), cysteine + proteases (CP-2), and metalloproteases (MEP-1), the first of which is known + to digest Hb. We now show that Hb is degraded by a multi-enzyme, synergistic + cascade of proteolysis. Recombinant APR-1 and CP-2, but not MEP-1, digested + native Hb and denatured globin. MEP-1, however, did cleave globin fragments + that had undergone prior digestion by APR-1 and CP-2. Proteolytic cleavage + sites within the Hb \u03b1 and \u03b2 chains were determined for the three + enzymes, identifying a total of 131 cleavage sites. By scanning synthetic + combinatorial peptide libraries with each enzyme, we compared the preferred + residues cleaved in the libraries with the known cleavage sites within Hb. + The semi-ordered pathway of Hb digestion described here is surprisingly similar + to that used by Plasmodium to digest Hb and provides a potential mechanism + by which these hemoglobinases are efficacious vaccines in animal models of + hookworm infection.", "venue": "Journal of Biological Chemistry", "year": + 2004, "referenceCount": 110, "citationCount": 162, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925820731820/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2004-08-20", "journal": {"volume": + "279", "pages": "35950 - 35957", "name": "Journal of Biological Chemistry"}, + "authors": [{"authorId": "34420936", "name": "A. Williamson"}, {"authorId": + "4393302", "name": "P. Lecchi"}, {"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "47634131", "name": "Youngchool Choe"}, {"authorId": "5943884", + "name": "P. Hotez"}, {"authorId": "3274892", "name": "J. McKerrow"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "39360449", "name": "M. Sajid"}, + {"authorId": "2143214", "name": "C. Craik"}, {"authorId": "145322315", "name": + "A. Loukas"}]}, {"paperId": "54bbd1b10ccd68093a9fdca8131c7321c5ca6bd9", "externalIds": + {"MAG": "2059370277", "DOI": "10.1016/J.YMETH.2003.10.003", "CorpusId": 27365039, + "PubMed": "15003602"}, "corpusId": 27365039, "publicationVenue": {"id": "054ddb2c-47fb-4de8-acfd-38566bec5015", + "name": "Methods", "type": "journal", "issn": "1046-2023", "url": "https://www.journals.elsevier.com/methods/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/10462023"]}, + "url": "https://www.semanticscholar.org/paper/54bbd1b10ccd68093a9fdca8131c7321c5ca6bd9", + "title": "Using peptide libraries to identify optimal cleavage motifs for + proteolytic enzymes.", "abstract": null, "venue": "Methods", "year": 2004, + "referenceCount": 29, "citationCount": 26, "influentialCitationCount": 0, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2004-04-01", "journal": {"volume": "32 4", "pages": "\n 398-405\n ", + "name": "Methods"}, "authors": [{"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "5de40039ce053e4f3318613990173aed85e34417", + "externalIds": {"MAG": "2085293179", "DOI": "10.1016/S0092-8674(04)00041-8", + "CorpusId": 17178990, "PubMed": "15055580"}, "corpusId": 17178990, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/5de40039ce053e4f3318613990173aed85e34417", + "title": "ZIP codes for delivering SH2 domains", "abstract": null, "venue": + "Cell", "year": 2004, "referenceCount": 20, "citationCount": 26, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle", "LettersAndComments"], + "publicationDate": "2004-01-23", "journal": {"volume": "116", "pages": "S41-S43", + "name": "Cell"}, "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "77755f94685bc59b111847c601f64a26ceac6b2b", + "externalIds": {"DOI": "10.1038/431128b", "CorpusId": 4394539}, "corpusId": + 4394539, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/77755f94685bc59b111847c601f64a26ceac6b2b", + "title": "New and revised textbooks", "abstract": null, "venue": "", "year": + 2004, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Education", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "431", "pages": "128", + "name": "Nature"}, "authors": [{"authorId": "2339651", "name": "B. Manning"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "7a8f1e10aa06c50b916669cb6fe96144f6c6db69", + "externalIds": {"MAG": "2780362317", "CorpusId": 171978686}, "corpusId": 171978686, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7a8f1e10aa06c50b916669cb6fe96144f6c6db69", + "title": "Activation directe de la kinase activee par l''amp reposant sur + l''utilisation de la kinase lkb1, suppresseur de tumeurs", "abstract": "L''invention + concerne la modulation de l''activite de la kinase-proteine LKB1 ou AMP pour + le traitement de certains troubles, y compris le diabete et le cancer. L''invention + concerne egalement la detection d''agents qui modulent l''activite consideree, + utiles pour le traitement du diabete et du cancer, et elle concerne aussi + l''elaboration de composes pour le traitement du diabete et du cancer.", "venue": + "", "year": 2004, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}], "publicationTypes": + null, "publicationDate": "2004-09-09", "journal": null, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2060344437", "name": "Reuben + J. Shaw"}, {"authorId": "5974412", "name": "N. Bardeesy"}, {"authorId": "5593407", + "name": "R. DePinho"}]}, {"paperId": "81c3ec79398ca668a0957687cfb90fb2ada282cc", + "externalIds": {"MAG": "2474540200", "CorpusId": 10264526, "PubMed": "16970176"}, + "corpusId": 10264526, "publicationVenue": {"id": "fa938a14-1042-4a8e-92f4-8bca2693dc6d", + "name": "The Harvey lectures", "type": "journal", "alternate_names": ["Harvey + Lect", "Harvey lect", "Harvey Lectures"], "issn": "0073-0874"}, "url": "https://www.semanticscholar.org/paper/81c3ec79398ca668a0957687cfb90fb2ada282cc", + "title": "The role of phosphoinositide 3-kinase in human disease.", "abstract": + null, "venue": "The Harvey lectures", "year": 2004, "referenceCount": 0, "citationCount": + 24, "influentialCitationCount": 2, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": null, "journal": {"volume": "100", "pages": + "\n 103-22\n ", "name": "Harvey lectures"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "936a8cc748f8978c2799d3ea919759912657d5f6", + "externalIds": {"MAG": "2129777487", "DOI": "10.1073/PNAS.0404720101", "CorpusId": + 10531919, "PubMed": "15302935"}, "corpusId": 10531919, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/936a8cc748f8978c2799d3ea919759912657d5f6", + "title": "Large-scale characterization of HeLa cell nuclear phosphoproteins.", + "abstract": "Determining the site of a regulatory phosphorylation event is + often essential for elucidating specific kinase-substrate relationships, providing + a handle for understanding essential signaling pathways and ultimately allowing + insights into numerous disease pathologies. Despite intense research efforts + to elucidate mechanisms of protein phosphorylation regulation, efficient, + large-scale identification and characterization of phosphorylation sites remains + an unsolved problem. In this report we describe an application of existing + technology for the isolation and identification of phosphorylation sites. + By using a strategy based on strong cation exchange chromatography, phosphopeptides + were enriched from the nuclear fraction of HeLa cell lysate. From 967 proteins, + 2,002 phosphorylation sites were determined by tandem MS. This unprecedented + large collection of sites permitted a detailed accounting of known and unknown + kinase motifs and substrates.", "venue": "Proceedings of the National Academy + of Sciences of the United States of America", "year": 2004, "referenceCount": + 49, "citationCount": 1359, "influentialCitationCount": 84, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc514446?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2004-08-17", "journal": {"volume": + "101 33", "pages": "\n 12130-5\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "4424720", "name": "S. Beausoleil"}, {"authorId": "6432355", + "name": "Mark P. Jedrychowski"}, {"authorId": "48917076", "name": "Daniel + Schwartz"}, {"authorId": "34117028", "name": "J. Elias"}, {"authorId": "1705488", + "name": "J. Vill\u00e9n"}, {"authorId": "47786895", "name": "Jiaxu Li"}, {"authorId": + "32650867", "name": "M. Cohn"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2665934", "name": "S. Gygi"}]}, {"paperId": "9effed1e63b6adfafa650fa10b4ccf2b56b95d53", + "externalIds": {"CorpusId": 36824738, "PubMed": "23573644"}, "corpusId": 36824738, + "publicationVenue": {"id": "66fa3a04-1561-48ac-8933-39a60b63cfad", "name": + "Drug Discovery Today", "type": "journal", "alternate_names": ["Drug Discov + Today"], "issn": "1359-6446", "url": "http://www.drugdiscoverytoday.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/13596446"]}, + "url": "https://www.semanticscholar.org/paper/9effed1e63b6adfafa650fa10b4ccf2b56b95d53", + "title": "Peptide libraries: at the crossroads of proteomics and bioinformatics.", + "abstract": "Peptide libraries offer a valuable means for providing functional + information regarding protein-modifying enzymes and protein interaction domains. + Library approaches have become increasingly useful as high-throughput strategies + for the analysis of large numbers of new proteins identified as a result of + genome-sequencing efforts. Recent developments in the field have produced + faster methods with broadened applicability. Crucially, new computational + and biochemical tools have emerged that facilitate identification of interaction + partners and substrates for proteins on the basis of their peptide selectivity + profiles. Such combinations of proteomics-scale experimental approaches with + bioinformatics tools hold great promise for the elucidation of protein interaction + networks and signal transduction pathways in living cells.", "venue": "Drug + Discovery Today", "year": 2004, "referenceCount": 0, "citationCount": 11, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": null, + "journal": {"volume": "9 2 Suppl", "pages": "\n S47-52\n ", + "name": "Drug discovery today"}, "authors": [{"authorId": "25581223", "name": + "B. Turk"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "a4c2f30ce709a0e76582e60a4e11c3e00b1de83d", + "externalIds": {"MAG": "2124099460", "PubMedCentral": "2172303", "DOI": "10.1083/jcb.200404150", + "CorpusId": 9957390, "PubMed": "15249580"}, "corpusId": 9957390, "publicationVenue": + {"id": "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/a4c2f30ce709a0e76582e60a4e11c3e00b1de83d", + "title": "A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast", + "abstract": "The mammalian tumor suppressor, phosphatase and tensin homologue + deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating + phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a + homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). + This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) + lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher + eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, + upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at levels + comparable to those in mammalian cells, indicating that a pathway exists for + synthesis of this lipid and that the S. pombe ptn1, like mammalian PTEN, suppresses + PI(3,4,5)P3 levels. By examining various mutants, we show that synthesis of + PI(3,4,5)P3 in S. pombe requires the class III phosphoinositide 3-kinase, + vps34p, and the phosphatidylinositol-4-phosphate 5-kinase, its3p, but does + not require the phosphatidylinositol-3-phosphate 5-kinase, fab1p. These studies + suggest that a pathway for PI(3,4,5)P3 synthesis downstream of a class III + phosphoinositide 3-kinase evolved before the appearance of class I phosphoinositide + 3-kinases.", "venue": "Journal of Cell Biology", "year": 2004, "referenceCount": + 33, "citationCount": 88, "influentialCitationCount": 7, "isOpenAccess": true, + "openAccessPdf": {"url": "http://jcb.rupress.org/content/166/2/205.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2004-07-19", "journal": {"volume": + "166", "pages": "205 - 211", "name": "The Journal of Cell Biology"}, "authors": + [{"authorId": "48850640", "name": "P. Mitra"}, {"authorId": "2108307841", + "name": "Yingjie Zhang"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "4242861", "name": "Maria P Ivshina"}, {"authorId": "144637141", "name": "D. + McCollum"}, {"authorId": "39444034", "name": "J. Nunnari"}, {"authorId": "40314991", + "name": "G. Hendricks"}, {"authorId": "5196339", "name": "M. L. Kerr"}, {"authorId": + "123039768", "name": "S. Field"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1715886", "name": "A. Ross"}]}, {"paperId": "b260087c48d85b7488519b1f54fb10cdeae2a0e4", + "externalIds": {"MAG": "1992257057", "DOI": "10.1016/J.CCR.2004.06.007", "CorpusId": + 13646157, "PubMed": "15261145"}, "corpusId": 13646157, "publicationVenue": + {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", "name": "Cancer Cell", "type": + "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/b260087c48d85b7488519b1f54fb10cdeae2a0e4", + "title": "The LKB1 tumor suppressor negatively regulates mTOR signaling.", + "abstract": null, "venue": "Cancer Cell", "year": 2004, "referenceCount": + 60, "citationCount": 1078, "influentialCitationCount": 68, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S1535610804001771/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2004-07-01", "journal": {"volume": + "6 1", "pages": "\n 91-9\n ", "name": "Cancer cell"}, "authors": + [{"authorId": "4426388", "name": "R. Shaw"}, {"authorId": "5974412", "name": + "N. Bardeesy"}, {"authorId": "2339651", "name": "B. Manning"}, {"authorId": + "5308858", "name": "L. Lopez"}, {"authorId": "15440166", "name": "Monica Kosmatka"}, + {"authorId": "5593407", "name": "R. DePinho"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "d27c7fe39a2eb2936c6bbda791ef4749783f7a3d", "externalIds": + {"MAG": "2102891343", "DOI": "10.1073/PNAS.0308061100", "CorpusId": 9910278, + "PubMed": "14985505"}, "corpusId": 9910278, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/d27c7fe39a2eb2936c6bbda791ef4749783f7a3d", + "title": "The tumor suppressor LKB1 kinase directly activates AMP-activated + kinase and regulates apoptosis in response to energy stress.", "abstract": + "AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular + energy status found in all eukaryotic cells. AMPK is activated by stimuli + that increase the cellular AMP/ATP ratio. Essential to activation of AMPK + is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity + in mammalian cells has remained elusive. Here we present biochemical and genetic + evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated + in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of + AMPK activation in several mammalian cell types. We show that LKB1 directly + phosphorylates Thr-172 of AMPKalpha in vitro and activates its kinase activity. + LKB1-deficient murine embryonic fibroblasts show nearly complete loss of Thr-172 + phosphorylation and downstream AMPK signaling in response to a variety of + stimuli that activate AMPK. Reintroduction of WT, but not kinase-dead, LKB1 + into these cells restores AMPK activity. Furthermore, we show that LKB1 plays + a biologically significant role in this pathway, because LKB1-deficient cells + are hypersensitive to apoptosis induced by energy stress. On the basis of + these results, we propose a model to explain the apparent paradox that LKB1 + is a tumor suppressor, yet cells lacking LKB1 are resistant to cell transformation + by conventional oncogenes and are sensitive to killing in response to agents + that elevate AMP. The role of LKB1/AMPK in the survival of a subset of genetically + defined tumor cells may provide opportunities for cancer therapeutics.", "venue": + "Proceedings of the National Academy of Sciences of the United States of America", + "year": 2004, "referenceCount": 36, "citationCount": 1726, "influentialCitationCount": + 140, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.pnas.org/content/101/10/3329.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2004-03-09", "journal": {"volume": "101 10", "pages": + "\n 3329-35\n ", "name": "Proceedings of the National Academy + of Sciences of the United States of America"}, "authors": [{"authorId": "4426388", + "name": "R. Shaw"}, {"authorId": "15440166", "name": "Monica Kosmatka"}, {"authorId": + "5974412", "name": "N. Bardeesy"}, {"authorId": "40318591", "name": "R. Hurley"}, + {"authorId": "10103203", "name": "L. Witters"}, {"authorId": "5593407", "name": + "R. DePinho"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d97c3714ddb39c27ec2aba7acd6dab0dcbffa756", "externalIds": {"MAG": "2010161321", + "DOI": "10.1038/nmeth708", "CorpusId": 4671684, "PubMed": "15782149"}, "corpusId": + 4671684, "publicationVenue": {"id": "099483df-e8f2-4bee-805d-8a69f07b6cbf", + "name": "Nature Methods", "type": "journal", "alternate_names": ["Nat Method"], + "issn": "1548-7091", "url": "http://www.nature.com/", "alternate_urls": ["http://www.nature.com/nmeth/index.html", + "https://www.nature.com/nmeth/", "http://www.nature.com/nmeth/authors/index.html#aims"]}, + "url": "https://www.semanticscholar.org/paper/d97c3714ddb39c27ec2aba7acd6dab0dcbffa756", + "title": "A rapid method for determining protein kinase phosphorylation specificity", + "abstract": null, "venue": "Nature Methods", "year": 2004, "referenceCount": + 16, "citationCount": 338, "influentialCitationCount": 5, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "2004-10-01", "journal": {"volume": + "1", "pages": "27-29", "name": "Nature Methods"}, "authors": [{"authorId": + "6742227", "name": "Jessica E. Hutti"}, {"authorId": "7844726", "name": "E. + Jarrell"}, {"authorId": "2116093125", "name": "James D. Chang"}, {"authorId": + "145759174", "name": "Derek W. Abbott"}, {"authorId": "4373748", "name": "P. + Storz"}, {"authorId": "145751285", "name": "A. Toker"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "25581223", "name": "B. Turk"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '228391' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:49 GMT + Via: + - 1.1 7577ef3efac8ae85ebf194f17e255fde.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - Cer5E9ck03M9FPQYXr3DnQEQtV2SxcBK48ya0t26v2g7WPNAXuiXyQ== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNObYHHpvHcF1og= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '228391' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:49 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - c40cbd2e-9bc1-4237-a417-06053e8d88d3 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=600&limit=100 + response: + body: + string: '{"offset": 600, "next": 700, "data": [{"paperId": "e2689bb0d08e79457bcb86722b8f9264b6c67115", + "externalIds": {"MAG": "2045743590", "DOI": "10.1016/j.cub.2004.12.032", "CorpusId": + 14331145, "PubMed": "15620648"}, "corpusId": 14331145, "publicationVenue": + {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", "name": "Current Biology", + "type": "journal", "alternate_names": ["Curr Biology"], "issn": "0960-9822", + "url": "http://www.current-biology.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/09609822"]}, + "url": "https://www.semanticscholar.org/paper/e2689bb0d08e79457bcb86722b8f9264b6c67115", + "title": "The Crohn''s Disease Protein, NOD2, Requires RIP2 in Order to Induce + Ubiquitinylation of a Novel Site on NEMO", "abstract": null, "venue": "Current + Biology", "year": 2004, "referenceCount": 75, "citationCount": 400, "influentialCitationCount": + 20, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0960982204009881/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "2004-12-29", "journal": {"volume": "14", "pages": + "2217-2227", "name": "Current Biology"}, "authors": [{"authorId": "145759174", + "name": "Derek W. Abbott"}, {"authorId": "3679332", "name": "A. Wilkins"}, + {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "ff47f5c6153e5eddc66deacab2a4d3b83b11ff6f", "externalIds": + {"MAG": "2120166232", "DOI": "10.1128/MCB.24.11.5080-5087.2004", "CorpusId": + 21869376, "PubMed": "15143198"}, "corpusId": 21869376, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/ff47f5c6153e5eddc66deacab2a4d3b83b11ff6f", + "title": "Increased Insulin Sensitivity and Reduced Adiposity in Phosphatidylinositol + 5-Phosphate 4-Kinase \u03b2\u2212/\u2212 Mice", "abstract": "ABSTRACT Phosphorylated + derivatives of the lipid phosphatidylinositol are known to play critical roles + in insulin response. Phosphatidylinositol 5-phosphate 4-kinases convert phosphatidylinositol + 5-phosphate to phosphatidylinositol 4,5-bis-phosphate. To understand the physiological + role of these kinases, we generated mice that do not express phosphatidylinositol + 5-phosphate 4-kinase \u03b2. These mice are hypersensitive to insulin and + have reduced body weights compared to wild-type littermates. While adult male + mice lacking phosphatidylinositol 5-phosphate 4-kinase \u03b2 have significantly + less body fat than wild-type littermates, female mice lacking phosphatidylinositol + 5-phosphate 4-kinase \u03b2 have increased insulin sensitivity in the presence + of normal adiposity. Furthermore, in vivo insulin-induced activation of the + protein kinase Akt is enhanced in skeletal muscle and liver from mice lacking + phosphatidylinositol 5-phosphate 4-kinase \u03b2. These results indicate that + phosphatidylinositol 5-phosphate 4-kinase \u03b2 plays a role in determining + insulin sensitivity and adiposity in vivo and suggest that inhibitors of this + enzyme may be useful in the treatment of type 2 diabetes.", "venue": "Molecular + and Cellular Biology", "year": 2004, "referenceCount": 37, "citationCount": + 112, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc416424?pdf=render", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2004-06-01", "journal": + {"volume": "24", "pages": "5080 - 5087", "name": "Molecular and Cellular Biology"}, + "authors": [{"authorId": "5493258", "name": "K. Lamia"}, {"authorId": "5675837", + "name": "O. Peroni"}, {"authorId": "1713886", "name": "Young-Bum Kim"}, {"authorId": + "4109960", "name": "L. Rameh"}, {"authorId": "1997179", "name": "B. Kahn"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "02b11866bdc03d7df7ea0efcd1ba7e2b1a5bb674", + "externalIds": {"MAG": "2036254130", "DOI": "10.1016/J.TIBS.2003.09.003", + "CorpusId": 6710251, "PubMed": "14607085"}, "corpusId": 6710251, "publicationVenue": + {"id": "bb8a9b7a-e5e7-4572-b03d-52d99bb0a3b7", "name": "TIBS -Trends in Biochemical + Sciences. Regular ed", "type": "journal", "alternate_names": ["TIB trends + Biochem Sci Regul ed", "Trends Biochem Sci", "Trends in Biochemical Sciences"], + "issn": "0968-0004", "url": "http://www.sciencedirect.com/science/journal/09680004"}, + "url": "https://www.semanticscholar.org/paper/02b11866bdc03d7df7ea0efcd1ba7e2b1a5bb674", + "title": "Rheb fills a GAP between TSC and TOR.", "abstract": null, "venue": + "TIBS -Trends in Biochemical Sciences. Regular ed", "year": 2003, "referenceCount": + 23, "citationCount": 476, "influentialCitationCount": 21, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "2003-11-01", "journal": {"volume": "28 11", "pages": "\n 573-6\n ", + "name": "Trends in biochemical sciences"}, "authors": [{"authorId": "2339651", + "name": "B. Manning"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "0d51b5d7c37676a2bd4c1999313ba9fcfbb2f9de", "externalIds": {"MAG": "2005408848", + "DOI": "10.1074/jbc.M208451200", "CorpusId": 6587928, "PubMed": "12435753"}, + "corpusId": 6587928, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/0d51b5d7c37676a2bd4c1999313ba9fcfbb2f9de", + "title": "Altered Signaling and Cell Cycle Regulation in Embryonal Stem Cells + with a Disruption of the Gene for Phosphoinositide 3-Kinase Regulatory Subunit + p85\u03b1*", "abstract": "The p85\u03b1 regulatory subunit of class IA phosphoinositide + 3-kinases (PI3K) is derived from the Pik3r1 gene, which also yields alternatively + spliced variants p50\u03b1 and p55\u03b1. It has been proposed that excess + monomeric p85 competes with functional PI3K p85-p110 heterodimers. We examined + embryonic stem (ES) cells with heterozygous and homozygous disruptions in + the Pik3r gene and found that wild type ES cells express virtually no monomeric + p85\u03b1. Although, IGF-1-stimulated PI3K activity associated with insulin + receptor substrates was unaltered in all cell lines, p85\u03b1-null ES cells + showed diminished protein kinase B activation despite increased PI3K activity + associated with the p85\u03b2 subunit. Furthermore, p85\u03b1-null cells demonstrated + growth retardation, increased frequency of apoptosis, and altered cell cycle + regulation with a G0/G1 cell cycle arrest and up-regulation of p27KIP, whereas + signaling through CREB and MAPK was enhanced. These phenotypes were reversed + by re-expression of p85\u03b1 via adenoviral gene transfer. Surprisingly, + all ES cell lines could be differentiated into adipocytes. In these differentiated + ES cells, however, compensatory p85\u03b2 signaling was lost in p85\u03b1-null + cells while increased signaling by CREB and MAPK was still observed. Thus, + loss of p85\u03b1 in ES cells induced alterations in IGF-1 signaling and regulation + of apoptosis and cell cycle but no defects in differentiation. However, differentiated + ES cells partially lost their ability for compensatory signaling at the level + of PI3K, which may explain some of the defects observed in mice with homozygous + deletion of the Pik3r1 gene.", "venue": "Journal of Biological Chemistry", + "year": 2003, "referenceCount": 34, "citationCount": 44, "influentialCitationCount": + 3, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/278/7/5099.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2003-02-14", "journal": {"volume": + "278", "pages": "5099 - 5108", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "7571475", "name": "D. Hallmann"}, {"authorId": "34646178", + "name": "Katja Tr\u00fcmper"}, {"authorId": "4645407", "name": "H. Trusheim"}, + {"authorId": "5177377", "name": "K. Ueki"}, {"authorId": "144391716", "name": + "C. Kahn"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6241317", + "name": "D. Fruman"}, {"authorId": "35006494", "name": "D. Ho\u0308rsch"}]}, + {"paperId": "17812e7141ae3cccb8d9293a95791acfc5517357", "externalIds": {"MAG": + "2056070148", "DOI": "10.1016/S0092-8674(03)00480-X", "CorpusId": 16506650, + "PubMed": "12859901"}, "corpusId": 16506650, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/17812e7141ae3cccb8d9293a95791acfc5517357", + "title": "The PHD Finger of the Chromatin-Associated Protein ING2 Functions + as a Nuclear Phosphoinositide Receptor", "abstract": null, "venue": "Cell", + "year": 2003, "referenceCount": 99, "citationCount": 488, "influentialCitationCount": + 32, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S009286740300480X/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2003-07-11", "journal": {"volume": + "114", "pages": "99-111", "name": "Cell"}, "authors": [{"authorId": "6896988", + "name": "O. Gozani"}, {"authorId": "6519399", "name": "P. Karuman"}, {"authorId": + "77190616", "name": "David R. Jones"}, {"authorId": "144052482", "name": "D. + Ivanov"}, {"authorId": "2054440913", "name": "J. Cha"}, {"authorId": "3877350", + "name": "A. Lugovskoy"}, {"authorId": "2072317320", "name": "C. L. Baird"}, + {"authorId": "50319426", "name": "Hong Zhu"}, {"authorId": "123039768", "name": + "S. Field"}, {"authorId": "6789492", "name": "S. Lessnick"}, {"authorId": + "8059403", "name": "J. Villase\u00f1or"}, {"authorId": "2080375177", "name": + "B. Mehrotra"}, {"authorId": "2118446510", "name": "Jian Chen"}, {"authorId": + "48149554", "name": "V. Rao"}, {"authorId": "3471778", "name": "J. Brugge"}, + {"authorId": "143978896", "name": "C. G. Ferguson"}, {"authorId": "3933495", + "name": "B. Payrastre"}, {"authorId": "3342884", "name": "D. Myszka"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "145241228", "name": "G. Wagner"}, + {"authorId": "9277588", "name": "N. Divecha"}, {"authorId": "2565299", "name": + "G. Prestwich"}, {"authorId": "40146895", "name": "Junying Yuan"}]}, {"paperId": + "3913bd1cbab8b412075d594a79910848c38348d6", "externalIds": {"MAG": "2109263914", + "DOI": "10.1016/S0960-9822(03)00506-2", "CorpusId": 6519150, "PubMed": "12906785"}, + "corpusId": 6519150, "publicationVenue": {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", + "name": "Current Biology", "type": "journal", "alternate_names": ["Curr Biology"], + "issn": "0960-9822", "url": "http://www.current-biology.com/", "alternate_urls": + ["http://www.sciencedirect.com/science/journal/09609822"]}, "url": "https://www.semanticscholar.org/paper/3913bd1cbab8b412075d594a79910848c38348d6", + "title": "Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, + Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward + Rheb", "abstract": null, "venue": "Current Biology", "year": 2003, "referenceCount": + 78, "citationCount": 1172, "influentialCitationCount": 71, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S0960982203005062/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "2003-08-05", "journal": {"volume": + "13", "pages": "1259-1268", "name": "Current Biology"}, "authors": [{"authorId": + "3870554", "name": "A. Tee"}, {"authorId": "2339651", "name": "B. Manning"}, + {"authorId": "1718769", "name": "Philippe P Roux"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4037343", "name": "J. Blenis"}]}, {"paperId": + "3e11d5142f925ead05a9d6b7e375bda0b9e2ba4b", "externalIds": {"MAG": "2077230170", + "DOI": "10.1042/BST0310573", "CorpusId": 10655005, "PubMed": "12773158"}, + "corpusId": 10655005, "publicationVenue": {"id": "9c7806c9-5d45-4670-86ed-e7e052ef142a", + "name": "Biochemical Society Transactions", "type": "journal", "alternate_names": + ["Biochem Soc Trans"], "issn": "0300-5127"}, "url": "https://www.semanticscholar.org/paper/3e11d5142f925ead05a9d6b7e375bda0b9e2ba4b", + "title": "United at last: the tuberous sclerosis complex gene products connect + the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin + (mTOR) signalling.", "abstract": "The molecular interplay between the phosphoinositide + 3-kinase (PI3K) pathway and mammalian target of rapamycin (mTOR) signalling + in the control of cell growth and proliferation has been the subject of much + interest and debate amongst cell biologists. A recent escalation of research + in this area has come from the discovery of the tuberous sclerosis complex + gene products, tuberin and hamartin, as central regulators of mTOR activation. + The PI3K effector Akt/protein kinase B has been found to directly phosphorylate + tuberin and is thereby thought to activate mTOR through inhibition of the + tuberin-hamartin complex. The many recent studies aimed at defining the molecular + nature of this revamped PI3K/Akt/mTOR pathway are reviewed here. The collective + data discussed have laid the groundwork for important new insights into the + many cancers caused by aberrant PI3K activation and the clinically challenging + tuberous sclerosis complex disease and have suggested a possible means of + treatment for both.", "venue": "Biochemical Society Transactions", "year": + 2003, "referenceCount": 0, "citationCount": 220, "influentialCitationCount": + 11, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "2003-06-01", "journal": {"volume": "31 Pt 3", "pages": "\n 573-8\n ", + "name": "Biochemical Society transactions"}, "authors": [{"authorId": "2339651", + "name": "B. Manning"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "4590e752389488799b6cf91719a026f756a225c3", "externalIds": {"MAG": "2755570915", + "CorpusId": 102730079}, "corpusId": 102730079, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/4590e752389488799b6cf91719a026f756a225c3", + "title": "Modulation de la phosphoinositide phosphate kinase de type ii$g(b)", + "abstract": "L''invention concerne des procedes pour moduler l''activite de + la phosphoinositide phosphate kinase de type II\u03b2 (PIPKII\u03b2) dans + le but de traiter des troubles associes a la PIPKII\u03b2. L''invention concerne + egalement des procedes pour identifier des agents candidats pour le traitement + de troubles associes a la PIPKII\u03b2.", "venue": "", "year": 2003, "referenceCount": + 1, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}], "publicationTypes": null, + "publicationDate": "2003-02-03", "journal": {"volume": "", "name": ""}, "authors": + [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5493258", "name": + "K. Lamia"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": "1997179", + "name": "B. Kahn"}, {"authorId": "5675837", "name": "O. Peroni"}]}, {"paperId": + "45aab1bbb6ace745f37ed22c04aefd63af66cfe8", "externalIds": {"MAG": "2048551141", + "DOI": "10.1016/S0092-8674(03)00725-6", "CorpusId": 15110841, "PubMed": "14532005"}, + "corpusId": 15110841, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/45aab1bbb6ace745f37ed22c04aefd63af66cfe8", + "title": "The Molecular Basis for Phosphodependent Substrate Targeting and + Regulation of Plks by the Polo-Box Domain", "abstract": null, "venue": "Cell", + "year": 2003, "referenceCount": 54, "citationCount": 734, "influentialCitationCount": + 63, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867403007256/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2003-10-03", "journal": {"volume": "115", "pages": "83-95", + "name": "Cell"}, "authors": [{"authorId": "35398419", "name": "A. Elia"}, + {"authorId": "5757608", "name": "P. Rellos"}, {"authorId": "4551084", "name": + "L. Haire"}, {"authorId": "2066447044", "name": "Jerry W. Chao"}, {"authorId": + "4379012", "name": "Frank J. Ivins"}, {"authorId": "3953017", "name": "K. + Hoepker"}, {"authorId": "40028226", "name": "Duaa H. Mohammad"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4189482", "name": "S. Smerdon"}, + {"authorId": "88402408", "name": "M. Yaffe"}]}, {"paperId": "8086754eb7197795d478c7cb0b7dda18ca9e152d", + "externalIds": {"CorpusId": 11300729, "PubMed": "14504291"}, "corpusId": 11300729, + "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": + "Journal of Biological Chemistry", "type": "journal", "alternate_names": ["J + Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/8086754eb7197795d478c7cb0b7dda18ca9e152d", + "title": "Positive and negative roles of p85 alpha and p85 beta regulatory + subunits of phosphoinositide 3-kinase in insulin signaling.", "abstract": + "Class IA phosphoinositide (PI) 3-kinase is composed of a p110 catalytic subunit + and a p85 regulatory subunit and plays a pivotal role in insulin signaling. + To explore the physiological roles of two major regulatory isoforms, p85 alpha + and p85 beta, we have established brown adipose cell lines with disruption + of the Pik3r1 or Pik3r2 gene. Pik3r1-/- (p85 alpha-/-) cells show a 70% reduction + of p85 protein and a parallel reduction of p110. These cells have a 50% decrease + in PI 3-kinase activity and a 30% decrease in Akt activity, leading to decreased + insulin-induced glucose uptake and anti-apoptosis. Pik3r2-/- (p85 beta-/-) + cells show a 25% reduction of p85 protein but normal levels of p85-p110 and + PI 3-kinase activity, supporting the fact that p85 is more abundant than p110 + in wild type. p85 beta-/- cells, however, exhibit significantly increased + insulin-induced Akt activation, leading to increased anti-apoptosis. Reconstitution + experiments suggest that the discrepancy between PI 3-kinase activity and + Akt activity is at least in part due to the p85-dependent negative regulation + of downstream signaling of PI 3-kinase. Indeed, both p85 alpha-/- cells and + p85 beta-/- cells exhibit significantly increased insulin-induced glycogen + synthase activation. p85 alpha-/- cells show decreased insulin-stimulated + Jun N-terminal kinase activity, which is restored by expression of p85 alpha, + p85 beta, or a p85 mutant that does not bind to p110, indicating the existence + of p85-dependent, but PI 3-kinase-independent, signaling pathway. Furthermore, + a reduction of p85 beta specifically increases insulin receptor substrate-2 + phosphorylation. Thus, p85 alpha and p85 beta modulate PI 3-kinase-dependent + signaling by multiple mechanisms and transmit signals independent of PI 3-kinase + activation.", "venue": "Journal of Biological Chemistry", "year": 2003, "referenceCount": + 0, "citationCount": 102, "influentialCitationCount": 5, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Computer Science", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "278 48", "pages": "\n 48453-66\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "5177377", + "name": "K. Ueki"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "7777071", "name": "C. Yballe"}, {"authorId": "48775825", "name": "M. Fasshauer"}, + {"authorId": "50073811", "name": "J. Klein"}, {"authorId": "1928077", "name": + "T. Asano"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "144391716", + "name": "C. Kahn"}]}, {"paperId": "80ea372d65d908cbe36badc84c19970ab039129a", + "externalIds": {"MAG": "2141732393", "DOI": "10.1074/JBC.M308659200", "CorpusId": + 27322516, "PubMed": "14512424"}, "corpusId": 27322516, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/80ea372d65d908cbe36badc84c19970ab039129a", + "title": "Binding Specificity and Regulation of the Serine Protease and PDZ + Domains of HtrA2/Omi*", "abstract": "Inhibitor of apoptosis proteins (IAPs) + prevent apoptosis through direct inhibition of caspases. The serine protease + HtrA2/Omi has an amino-terminal IAP interaction motif like that found in Reaper, + which displaces IAPs from caspases, leading to enhanced caspase activity. + The cell death-promoting properties of HtrA2/Omi are not only exerted through + its capacity to oppose IAP inhibition of caspases but also through its integral + serine protease activity. We have used peptide libraries to determine the + optimal substrate sequence for cleavage by HtrA2 and also the preferred binding + sequence for its PDZ domain. Using these peptides, we show that the PDZ domain + of HtrA2/Omi suppresses the proteolytic activity unless it is engaged by a + binding partner. Subjecting HtrA2/Omi to heat shock treatment also increases + its protease activity. Unexpectedly, binding of X-linked inhibitor of apoptosis + protein (XIAP) to the Reaper motif of HtrA2/Omi results in a marked increase + in proteolytic activity, suggesting a new role for IAPs. When HtrA2/Omi is + released from mitochondria following an apoptotic stimulus, binding to IAPs + may switch their function from caspase inhibition to serine protease activation. + Thus although IAP overexpression can suppress caspase activation, it could + have the opposite effect on HtrA2/Omi-dependent cell death. This, together + with the ability of HtrA2/Omi to degrade IAPs, may limit the overall cellular + protection that can be provided by these proteins.", "venue": "Journal of + Biological Chemistry", "year": 2003, "referenceCount": 22, "citationCount": + 121, "influentialCitationCount": 13, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/article/S0021925820757194/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2003-12-05", "journal": {"volume": "278", "pages": "49417 + - 49427", "name": "Journal of Biological Chemistry"}, "authors": [{"authorId": + "143931284", "name": "L. Martins"}, {"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "5042757", "name": "V. Cowling"}, {"authorId": "39732969", "name": + "Annabel Borg"}, {"authorId": "7844726", "name": "E. Jarrell"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6851395", "name": "J. Downward"}]}, + {"paperId": "83a5314df92758d2eb55945e6f05f5d0df387ba2", "externalIds": {"MAG": + "2104640364", "DOI": "10.1242/jcs.00666", "CorpusId": 10295948, "PubMed": + "12876217"}, "corpusId": 10295948, "publicationVenue": {"id": "398b46b8-6014-4478-b7af-f477167f7bde", + "name": "Journal of Cell Science", "type": "journal", "alternate_names": ["J + Cell Sci"], "issn": "0021-9533", "url": "https://jcs.biologists.org/", "alternate_urls": + ["http://jcs.biologists.org/"]}, "url": "https://www.semanticscholar.org/paper/83a5314df92758d2eb55945e6f05f5d0df387ba2", + "title": "Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and + vacuole maturation", "abstract": "Mammalian cell invasion by the protozoan + parasite, Trypanosoma cruzi, is facilitated by the activation of host cell + phosphatidylinositol 3 (PI 3)-kinases. We demonstrate that the well-characterized + Ca2+-regulated lysosome-mediated parasite entry pathway is abolished by wortmannin + pretreatment. In addition, we have characterized a novel route of T. cruzi + invasion unexpectedly revealed in the course of this study. For over a decade, + targeted exocytosis of lysosomes at the host cell plasma membrane was considered + as the primary mechanism for T. cruzi entry into non-professional phagocytic + cells. We now provide evidence that a significant fraction (50% or greater) + of invading T. cruzi trypomastigotes exploit an alternate actin-independent + entry pathway that involves formation of a tightly associated host cell plasma + membrane-derived vacuole enriched in the lipid products of class I PI 3-kinases, + PtdInsP3/PtdIns(3,4)P2. Initially devoid of lysosomal markers, the resultant + parasite-containing vacuoles gradually acquire lysosome associated membrane + protein 1 (lamp-1) and fluid phase endocytic tracer from the lysosomal compartment. + In striking contrast to latex bead phagosomes, few T. cruzi vacuoles associate + with the early endosomal marker, EEA1 and the ''maturation'' process becomes + refractory to PI 3-kinase inhibition immediately following parasite internalization. + Jointly, these data provide a new paradigm for T. cruzi invasion of non-professional + phagocytic cells and reveal a novel vacuole maturation process that appears + to bypass the requirement for EEA1.", "venue": "Journal of Cell Science", + "year": 2003, "referenceCount": 84, "citationCount": 155, "influentialCitationCount": + 13, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2003-09-01", "journal": {"volume": "116", "pages": "3611 - 3622", "name": + "Journal of Cell Science"}, "authors": [{"authorId": "34644153", "name": "A. + Woolsey"}, {"authorId": "12644017", "name": "Lisa Sunwoo"}, {"authorId": "145385785", + "name": "C. Petersen"}, {"authorId": "3710358", "name": "S. Brachmann"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5164780", "name": "B. Burleigh"}]}, + {"paperId": "8748a4c4c86885c285d6eac02b54c1325f5b5e6d", "externalIds": {"CorpusId": + 249604594}, "corpusId": 249604594, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/8748a4c4c86885c285d6eac02b54c1325f5b5e6d", + "title": "Identification and Characterization of a High-Affinity Interaction + between v-Crk and Tyrosine-Phosphorylated Paxillin in CT 10-Transformed Fibroblasts", + "abstract": "The genome of avian sarcoma virus CT1O encodes a fusion protein + in which viral Gag sequences are fused to cellular Crk sequences containing + primarily Src homology 2 (SH2) and Src homology 3 (SH3) domains. Transformation + of chicken embryo fibroblasts (CEF) with the Gag-Crk fusion protein results + in the elevation of tyrosine phosphorylation on specific cellular proteins + with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, + respectively), an event which has been correlated with cell transformation. + In this study, we have identified the 70-kDa yrosine-phosphorylated protein + in CT10-transformed CEF (CT10-CEF) as paxillin, a cytoskeletal protein suggested + to be important for organizing the focal adhesion. Tyrosinephosphorylated + paxillin was found to be complexed with v-Crk in vivo as evident from coimmunoprecipitation + studies. Moreover, a bacterially expressed recombinant glutathione S-transferase + (GST)-CrkSH2 fragment bound paxillin in vitro with a subnanomolar affinity, + suggesting that the SH2 domain of v-Crk is sufficient for binding. Mapping + of the sequence specificity of a GST-CrkSH2 fusion protein with a partially + degenerate phosphopeptide library determined a motif consisting ofpYDXP, and + in competitive coprecipitation studies, an acetylated A(p)YDAPA hexapeptide + was able to quantitatively inhibit the binding of GST-CrkSH2 to paxillin and + p130, suggesting that it meets the minimal structural requirements necessary + for the interaction of CrkSH2 with physiological targets. To investigate the + mechanism by which v-Crk elevates the tyrosine phosphorylation of paxillin + in vivo, we have treated normal CEF and CT10-CEF with sodium vanadate to inhibit + protein tyrosine phosphatase activity. Although many additional cellular proteins + became hyperphosphorylated on tyrosine in the vanadate-treated CT10-CEF, the + GST-CrkSH2 fragment still bound preferentially to the paxillin and 130-kDa + proteins, suggesting a high degree of specificity in the interaction of CrkSH2 + with these proteins. Paxillin phosphorylation was highly sensitive to vanadate + treatment in both normal CEF and CT1O-CEF, and the elevation in tyrosine phosphorylation + resulted in increased binding to GST-CrkSH2. Moreover, binding of full-length + GST-v-Crk to tyrosine-phosphorylated paxillin in vitro protected paxillin + from dephosphorylation by cellular protein tyrosine phosphatase activity. + These data suggest that paxillin is involved in a highly dynamic kinase-phosphatase + interplay in normal CEF and that v-Crk binding may interrupt this balance + to increase the steady-state level of tyrosine phosphorylation. By contrast, + the 130-kDa protein was not tyrosine phosphorylated upon vanadate treatment + of normal CEF and only weakly affected in the CT10-CEF, suggesting that a + different mechanism may be involved in its phosphorylation.", "venue": "", + "year": 2003, "referenceCount": 51, "citationCount": 10, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "35085909", + "name": "B. Raymond"}, {"authorId": "29963164", "name": "Birge"}, {"authorId": + "143676959", "name": "J. Fajardo"}, {"authorId": "2070859071", "name": "Charles"}, + {"authorId": "2102743601", "name": "Reichman"}, {"authorId": "6731027", "name": + "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1973946", "name": "H. Hanafusa"}]}, {"paperId": "8af8f11d66b0ddffa6655cd36d622567add83211", + "externalIds": {"MAG": "2117263216", "DOI": "10.1016/S1535-6108(03)00248-4", + "CorpusId": 1101699, "PubMed": "14585353"}, "corpusId": 1101699, "publicationVenue": + {"id": "11e469cb-37ad-487e-b0ab-d26e82037c22", "name": "Cancer Cell", "type": + "journal", "issn": "1535-6108", "url": "http://www.sciencedirect.com/science/journal/15356108", + "alternate_urls": ["http://www.cancercell.org/"]}, "url": "https://www.semanticscholar.org/paper/8af8f11d66b0ddffa6655cd36d622567add83211", + "title": "Targeting the PI3K-Akt pathway in human cancer: rationale and promise.", + "abstract": null, "venue": "Cancer Cell", "year": 2003, "referenceCount": + 66, "citationCount": 1373, "influentialCitationCount": 49, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S1535610803002484/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2003-10-01", "journal": + {"volume": "4 4", "pages": "\n 257-62\n ", "name": "Cancer + cell"}, "authors": [{"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "2339651", "name": "B. Manning"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "970633c231a6829e99e743d74ff874369f5c0a2a", "externalIds": {"MAG": + "2019225962", "DOI": "10.1016/S1367-5931(02)00004-2", "CorpusId": 20997727, + "PubMed": "12547431"}, "corpusId": 20997727, "publicationVenue": {"id": "20ab0f70-2011-4d23-a963-eb604a78ae7d", + "name": "Current Opinion in Chemical Biology", "type": "journal", "alternate_names": + ["Curr Opin Chem Biology"], "issn": "1367-5931", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/601299/description#description", + "alternate_urls": ["https://www.journals.elsevier.com/current-opinion-in-chemical-biology", + "http://www.sciencedirect.com/science/journal/13675931"]}, "url": "https://www.semanticscholar.org/paper/970633c231a6829e99e743d74ff874369f5c0a2a", + "title": "Peptide libraries: at the crossroads of proteomics and bioinformatics.", + "abstract": null, "venue": "Current Opinion in Chemical Biology", "year": + 2003, "referenceCount": 50, "citationCount": 34, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "2003-02-01", "journal": {"volume": "7 1", "pages": "\n 84-90\n ", + "name": "Current opinion in chemical biology"}, "authors": [{"authorId": "25581223", + "name": "B. Turk"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "9983660858c0acd8d53cbf2ec80ac170810f2622", "externalIds": {"MAG": "2039179232", + "DOI": "10.1074/jbc.M305602200", "CorpusId": 84382770}, "corpusId": 84382770, + "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": + "Journal of Biological Chemistry", "type": "journal", "alternate_names": ["J + Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/9983660858c0acd8d53cbf2ec80ac170810f2622", + "title": "Positive and Negative Roles of p85\u03b1 and p85\u03b2 Regulatory + Subunits of Phosphoinositide 3-Kinase in Insulin Signaling*", "abstract": + "Class IA phosphoinositide (PI) 3-kinase is composed of a p110 catalytic subunit + and a p85 regulatory subunit and plays a pivotal role in insulin signaling. + To explore the physiological roles of two major regulatory isoforms, p85\u03b1 + and p85\u03b2, we have established brown adipose cell lines with disruption + of the Pik3r1 or Pik3r2 gene. Pik3r1-/- (p85\u03b1-/-) cells show a 70% reduction + of p85 protein and a parallel reduction of p110. These cells have a 50% decrease + in PI 3-kinase activity and a 30% decrease in Akt activity, leading to decreased + insulin-induced glucose uptake and anti-apoptosis. Pik3r2-/- (p85\u03b2-/-) + cells show a 25% reduction of p85 protein but normal levels of p85-p110 and + PI 3-kinase activity, supporting the fact that p85 is more abundant than p110 + in wild type. p85\u03b2-/- cells, however, exhibit significantly increased + insulin-induced Akt activation, leading to increased anti-apoptosis. Reconstitution + experiments suggest that the discrepancy between PI 3-kinase activity and + Akt activity is at least in part due to the p85-dependent negative regulation + of downstream signaling of PI 3-kinase. Indeed, both p85\u03b1-/- cells and + p85\u03b2-/- cells exhibit significantly increased insulin-induced glycogen + synthase activation. p85\u03b1-/- cells show decreased insulin-stimulated + Jun N-terminal kinase activity, which is restored by expression of p85\u03b1, + p85\u03b2, or a p85 mutant that does not bind to p110, indicating the existence + of p85-dependent, but PI 3-kinase-independent, signaling pathway. Furthermore, + a reduction of p85\u03b2 specifically increases insulin receptor substrate-2 + phosphorylation. Thus, p85\u03b1 and p85\u03b2 modulate PI 3-kinase-dependent + signaling by multiple mechanisms and transmit signals independent of PI 3-kinase + activation.", "venue": "Journal of Biological Chemistry", "year": 2003, "referenceCount": + 54, "citationCount": 139, "influentialCitationCount": 5, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/278/48/48453.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "2003-11-28", "journal": {"volume": "278", "pages": + "48453 - 48466", "name": "Journal of Biological Chemistry"}, "authors": [{"authorId": + "5177377", "name": "K. Ueki"}, {"authorId": "6241317", "name": "D. Fruman"}, + {"authorId": "7777071", "name": "C. Yballe"}, {"authorId": "48775825", "name": + "M. Fasshauer"}, {"authorId": "50073811", "name": "J. Klein"}, {"authorId": + "1928077", "name": "T. Asano"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "144391716", "name": "C. Kahn"}]}, {"paperId": "a8aa9d511dd2b19cefa903a2ab23b8ed0b59a7b7", + "externalIds": {"MAG": "1994652412", "DOI": "10.1126/SCIENCE.1079079", "CorpusId": + 1952408, "PubMed": "12595692"}, "corpusId": 1952408, "publicationVenue": {"id": + "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": "journal", + "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/a8aa9d511dd2b19cefa903a2ab23b8ed0b59a7b7", + "title": "Proteomic Screen Finds pSer/pThr-Binding Domain Localizing Plk1 + to Mitotic Substrates", "abstract": "We have developed a proteomic approach + for identifying phosphopeptide binding domains that modulate kinase-dependent + signaling pathways. An immobilized library of partially degenerate phosphopeptides + biased toward a particular protein kinase phosphorylation motif is used to + isolate phospho-binding domains that bind to proteins phosphorylated by that + kinase. Applying this approach to cyclin-dependent kinases (Cdks), we identified + the polo-box domain (PBD) of the mitotic kinase polo-like kinase 1 (Plk1) + as a specific phosphoserine (pSer) or phosphothreonine (pThr) binding domain + and determined its optimal binding motif. This motif is present in known Plk1 + substrates such as Cdc25, and an optimal phosphopeptide containing the motif + disrupted PBD-substrate binding and localization of the PBD to centrosomes. + This finding reveals how Plk1 can localize to specific sites within cells + in response to Cdk phosphorylation at those sites and provides a structural + mechanism for targeting the Plk1 kinase domain to its substrates.", "venue": + "Science", "year": 2003, "referenceCount": 24, "citationCount": 696, "influentialCitationCount": + 87, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2003-02-21", "journal": {"volume": + "299", "pages": "1228 - 1231", "name": "Science"}, "authors": [{"authorId": + "35398419", "name": "A. Elia"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "88402408", "name": "M. Yaffe"}]}, {"paperId": "be69cf71571b3c65fbfb2927c2820cca1ed1d7b7", + "externalIds": {"MAG": "2037308821", "DOI": "10.1074/JBC.M302094200", "CorpusId": + 24820838, "PubMed": "12734182"}, "corpusId": 24820838, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/be69cf71571b3c65fbfb2927c2820cca1ed1d7b7", + "title": "Use of RNA Interference-mediated Gene Silencing and Adenoviral Overexpression + to Elucidate the Roles of AKT/Protein Kinase B Isoforms in Insulin Actions*", + "abstract": "Insulin plays a central role in the regulation of glucose homeostasis + in part by stimulating glucose uptake and glycogen synthesis. The serine/threonine + protein kinase Akt has been proposed to mediate insulin signaling in several + processes. However, it is unclear whether Akt is involved in insulin-stimulated + glucose uptake and which isoforms of Akt are responsible for each insulin + action. We confirmed that expression of a constitutively active Akt, using + an adenoviral expression vector, promoted translocation of glucose transporter + 4 (GLUT4) to plasma membrane, 2-deoxyglucose (2-DG) uptake, and glycogen synthesis + in both Chinese hamster ovary cells and 3T3-L1 adipocytes. Inhibition of Akt + either by adenoviral expression of a dominant negative Akt or by the introduction + of synthetic 21-mer short interference RNA against Akt markedly reduced insulin-stimulated + GLUT4 translocation, 2-DG uptake, and glycogen synthesis. Experiments with + isoform-specific short interference RNA revealed that Akt2, and Akt1 to a + lesser extent, has an essential role in insulin-stimulated GLUT4 translocation + and 2-DG uptake in both cell lines, whereas Akt1 and Akt2 contribute equally + to insulin-stimulated glycogen synthesis. These data suggest a prerequisite + role of Akt in insulin-stimulated glucose uptake and distinct functions among + Akt isoforms.", "venue": "Journal of Biological Chemistry", "year": 2003, + "referenceCount": 54, "citationCount": 219, "influentialCitationCount": 7, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925820845669/pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2003-07-25", "journal": {"volume": "278", "pages": "28312 - 28323", "name": + "Journal of Biological Chemistry"}, "authors": [{"authorId": "6207063", "name": + "T. Katome"}, {"authorId": "3091430", "name": "T. Obata"}, {"authorId": "35453046", + "name": "R. Matsushima"}, {"authorId": "5026168", "name": "N. Masuyama"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1955165", "name": + "Y. Gotoh"}, {"authorId": "46480734", "name": "K. Kishi"}, {"authorId": "3023951", + "name": "H. Shiota"}, {"authorId": "2081978", "name": "Y. Ebina"}]}, {"paperId": + "dd7118898f6b705ba06a870f2ecb5d85388f54bb", "externalIds": {"MAG": "1992190316", + "DOI": "10.1126/STKE.2122003TR8", "CorpusId": 83876605}, "corpusId": 83876605, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/dd7118898f6b705ba06a870f2ecb5d85388f54bb", + "title": "Growth Factors Bind Receptor Tyrosine Kinases to Stimulate Cell + Survival, Cell Division, Cell Growth, and Cytoskeletal Rearrangement", "abstract": + "These two animations show some of the molecular events associated with the + growth factors activation of receptor tyrosine kinases that leads to the stimulation + of phosphoinositide 3-kinase. In Animation 1, growth factors stimulate cell + survival and entry into the S phase of the cell cycle. In Animation 2, growth + factors stimulate the activation of proteins that regulate the cytoskeleton, + stimulation of protein synthesis, and stimulation of the Tec family of tyrosine + kinases. Animation 2 also shows how the action of phosphatases, such as PTEN, + terminates signaling and resets the system to receive a new stimulus. The + cellular processes illustrated include protein and lipid phosphorylation and + dephosphorylation, protein degradation, protein translocation, and regulation + of gene expression.", "venue": "Science''s STKE", "year": 2003, "referenceCount": + 0, "citationCount": 4, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2003-12-09", "journal": {"volume": + "2003", "pages": "tr8 - tr8", "name": "Science''s STKE"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "f48777af4c169b15a53c2c0f81dc04a9dc780a4d", + "externalIds": {"MAG": "2065989299", "DOI": "10.1073/pnas.1734038100", "CorpusId": + 24521062, "PubMed": "12897244"}, "corpusId": 24521062, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/f48777af4c169b15a53c2c0f81dc04a9dc780a4d", + "title": "The phosphatidylinositol (PI)-5-phosphate 4-kinase type II enzyme + controls insulin signaling by regulating PI-3,4,5-trisphosphate degradation", + "abstract": "Phosphatidylinositol-5-phosphate (PI-5-P) is a newly identified + phosphoinositide with characteristics of a signaling lipid but no known cellular + function. PI-5-P levels are controlled by the type II PI-5-P 4-kinases (PIP4K + IIs), a family of kinases that converts PI-5-P into phosphatidylinositol-4,5-bisphosphate + (PI-4,5-P2). The PI-5-P pathway is an alternative route for PI-4,5-P2 synthesis + as the bulk of this lipid is generated by the canonical pathway in which phosphatidylinositol-4-phosphate + (PI-4-P) is the intermediate. Here we examined the effect of activation of + the PI-5-P pathway on phosphoinositide 3-kinase (PI3K) signaling by expressing + PIP4K II\u03b2 in cells that lack this enzyme. Although PIP4K II generates + PI-4,5-P2, a substrate for PI3K, expression of this enzyme reduced rather + than increased phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) levels + in cells stimulated with insulin or cells expressing activated PI3K. This + reduction in PI-3,4,5-P3 levels resulted in decreased activation of the downstream + protein kinase, Akt/PKB. Consistent with these results, expression of IpgD, + a bacterial phosphatase that converts PI-4,5-P2 to PI-5-P, resulted in Akt + activation, and this effect was partially reversed by PIP4K II\u03b2. PIP4K + II\u03b2 expression did not impair insulin-dependent association of PI3K with + insulin receptor substrate 1 (IRS1) but abbreviated Akt activation, indicating + that PIP4K II regulates PI-3,4,5-P3 degradation rather than synthesis. These + data support a model in which the PI-5-P pathway controls insulin signaling + that leads to Akt activation by regulating a PI-3,4,5-P3 phosphatase.", "venue": + "Proceedings of the National Academy of Sciences of the United States of America", + "year": 2003, "referenceCount": 13, "citationCount": 119, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc187868?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2003-08-01", "journal": {"volume": + "100", "pages": "9867 - 9872", "name": "Proceedings of the National Academy + of Sciences of the United States of America"}, "authors": [{"authorId": "7238684", + "name": "V. Carricaburu"}, {"authorId": "5493258", "name": "K. Lamia"}, {"authorId": + "2061333591", "name": "Elizabeth Lo"}, {"authorId": "14794392", "name": "Laetitia + Favereaux"}, {"authorId": "3933495", "name": "B. Payrastre"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4109960", "name": "L. Rameh"}]}, + {"paperId": "fb04e214da3820c1ea8decfcf81735a1a859d7f5", "externalIds": {"DBLP": + "journals/nar/ObenauerCY03", "MAG": "2085037886", "DOI": "10.1093/nar/gkg584", + "CorpusId": 6939160, "PubMed": "12824383"}, "corpusId": 6939160, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/fb04e214da3820c1ea8decfcf81735a1a859d7f5", + "title": "Scansite 2.0: proteome-wide prediction of cell signaling interactions + using short sequence motifs", "abstract": "Scansite identifies short protein + sequence motifs that are recognized by modular signaling domains, phosphorylated + by protein Ser/Thr- or Tyr-kinases or mediate specific interactions with protein + or phospholipid ligands. Each sequence motif is represented as a position-specific + scoring matrix (PSSM) based on results from oriented peptide library and phage + display experiments. Predicted domain-motif interactions from Scansite can + be sequentially combined, allowing segments of biological pathways to be constructed + in silico. The current release of Scansite, version 2.0, includes 62 motifs + characterizing the binding and/or substrate specificities of many families + of Ser/Thr- or Tyr-kinases, SH2, SH3, PDZ, 14-3-3 and PTB domains, together + with signature motifs for PtdIns(3,4,5)P(3)-specific PH domains. Scansite + 2.0 contains significant improvements to its original interface, including + a number of new generalized user features and significantly enhanced performance. + Searches of all SWISS-PROT, TrEMBL, Genpept and Ensembl protein database entries + are now possible with run times reduced by approximately 60% when compared + with Scansite version 1.0. Scansite 2.0 allows restricted searching of species-specific + proteins, as well as isoelectric point and molecular weight sorting to facilitate + comparison of predictions with results from two-dimensional gel electrophoresis + experiments. Support for user-defined motifs has been increased, allowing + easier input of user-defined matrices and permitting user-defined motifs to + be combined with pre-compiled Scansite motifs for dual motif searching. In + addition, a new series of Sequence Match programs for non-quantitative user-defined + motifs has been implemented. Scansite is available via the World Wide Web + at http://scansite.mit.edu.", "venue": "Nucleic Acids Res.", "year": 2003, + "referenceCount": 17, "citationCount": 1634, "influentialCitationCount": 209, + "isOpenAccess": true, "openAccessPdf": {"url": "https://academic.oup.com/nar/article-pdf/31/13/3635/9487448/gkg584.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Computer Science", "Medicine"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Computer Science", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2003-07-01", "journal": {"volume": + "31 13", "pages": "\n 3635-41\n ", "name": "Nucleic acids + research"}, "authors": [{"authorId": "1750479", "name": "J. Obenauer"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "88402408", "name": "M. Yaffe"}]}, + {"paperId": "00a54f15b22dc76350926c43eaf245180e36cd7f", "externalIds": {"MAG": + "2036618934", "DOI": "10.1038/nature01304", "CorpusId": 4367083, "PubMed": + "12478301"}, "corpusId": 4367083, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/00a54f15b22dc76350926c43eaf245180e36cd7f", + "title": "Overview of the Alliance for Cellular Signaling", "abstract": null, + "venue": "Nature", "year": 2002, "referenceCount": 3, "citationCount": 125, + "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": {"url": + "https://www.nature.com/articles/nature01304.pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Review"], "publicationDate": "2002-12-12", "journal": {"volume": "420", "pages": + "703-706", "name": "Nature"}, "authors": [{"authorId": "2064172759", "name": + "A. Gilman"}, {"authorId": "4204614", "name": "M. Simon"}, {"authorId": "2324026", + "name": "H. Bourne"}, {"authorId": "48296505", "name": "B. A. Harris"}, {"authorId": + "46313934", "name": "Rochelle Long"}, {"authorId": "2693015", "name": "E. + Ross"}, {"authorId": "3572450", "name": "J. Stull"}, {"authorId": "5635705", + "name": "R. Taussig"}, {"authorId": "1756978", "name": "A. Arkin"}, {"authorId": + "2039872", "name": "M. Cobb"}, {"authorId": "36795799", "name": "J. Cyster"}, + {"authorId": "1801962", "name": "P. Devreotes"}, {"authorId": "6407990", "name": + "J. Ferrell"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "90028612", "name": "Michaela A. Gold"}, {"authorId": "145922021", "name": + "A. Weiss"}, {"authorId": "2258496", "name": "M. Berridge"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2184965", "name": "W. Catterall"}, + {"authorId": "10073478", "name": "S. Coughlin"}, {"authorId": "37933650", + "name": "E. Olson"}, {"authorId": "2109503620", "name": "Temple F. Smith"}, + {"authorId": "3471778", "name": "J. Brugge"}, {"authorId": "2149626", "name": + "D. Botstein"}, {"authorId": "30894895", "name": "J. Dixon"}, {"authorId": + "143683912", "name": "T. Hunter"}, {"authorId": "6412926", "name": "R. Lefkowitz"}, + {"authorId": "30576773", "name": "A. Pawson"}, {"authorId": "1808359", "name": + "P. Sternberg"}, {"authorId": "2681217", "name": "H. Varmus"}, {"authorId": + "145352433", "name": "S. Subramaniam"}, {"authorId": "2940708", "name": "R. + Sinkovits"}, {"authorId": "2109044140", "name": "Joshua Li"}, {"authorId": + "145409261", "name": "D. Mock"}, {"authorId": "2143391740", "name": "Yuhong + Ning"}, {"authorId": "145479946", "name": "Brian Saunders"}, {"authorId": + "4628331", "name": "P. Sternweis"}, {"authorId": "5312686", "name": "D. Hilgemann"}, + {"authorId": "145125922", "name": "R. Scheuermann"}, {"authorId": "48745949", + "name": "D. Decamp"}, {"authorId": "1833808", "name": "R. Hsueh"}, {"authorId": + "2148833271", "name": "Keng-mean Lin"}, {"authorId": "2072724163", "name": + "Yan G. Ni"}, {"authorId": "1951615", "name": "W. Seaman"}, {"authorId": "2058197293", + "name": "Paul C. Simpson"}, {"authorId": "1422413298", "name": "T. O\u2019Connell"}, + {"authorId": "2118979", "name": "T. Roach"}, {"authorId": "3314704", "name": + "Sangdun Choi"}, {"authorId": "1404956411", "name": "P. Eversole-Cire"}, {"authorId": + "143912759", "name": "I. Fraser"}, {"authorId": "6094460", "name": "M. Mumby"}, + {"authorId": "47827865", "name": "Yingming Zhao"}, {"authorId": "6159152", + "name": "D. Brekken"}, {"authorId": "6427016", "name": "Hongjun Shu"}, {"authorId": + "145284943", "name": "T. Meyer"}, {"authorId": "46670601", "name": "G. Chandy"}, + {"authorId": "144636585", "name": "W. Heo"}, {"authorId": "3586148", "name": + "J. Liou"}, {"authorId": "1403901937", "name": "N. O\u2019Rourke"}, {"authorId": + "24092362", "name": "M. Verghese"}, {"authorId": "46338677", "name": "S. Mumby"}, + {"authorId": "2112437092", "name": "Heping Han"}, {"authorId": "1772215", + "name": "H. Brown"}, {"authorId": "48165059", "name": "Jeffrey S. Forrester"}, + {"authorId": "2426618", "name": "P. Ivanova"}, {"authorId": "9215225", "name": + "S. Milne"}, {"authorId": "32314742", "name": "P. Casey"}, {"authorId": "145559386", + "name": "T. K. Harden"}, {"authorId": "145838187", "name": "J. Doyle"}, {"authorId": + "2053941089", "name": "M. L. Gray"}, {"authorId": "6485491", "name": "S. Michnick"}, + {"authorId": "144713191", "name": "M. Schmidt"}, {"authorId": "145527638", + "name": "M. Toner"}, {"authorId": "2822724", "name": "R. Tsien"}, {"authorId": + "40258057", "name": "Madhusudan Natarajan"}, {"authorId": "1710364", "name": + "R. Ranganathan"}, {"authorId": "4373034", "name": "G. R. Sambrano"}]}, {"paperId": + "143d55f2da249f69ecc5328a411a45447143039b", "externalIds": {"MAG": "2014187690", + "DOI": "10.1074/jbc.M205071200", "CorpusId": 12879881, "PubMed": "12119297"}, + "corpusId": 12879881, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/143d55f2da249f69ecc5328a411a45447143039b", + "title": "Peptide Substrate Specificities and Protein Cleavage Sites of Human + Endometase/Matrilysin-2/Matrix Metalloproteinase-26*", "abstract": "Human + endometase/matrilysin-2/matrix metalloproteinase-26 (MMP-26) is a novel epithelial + and cancer-specific metalloproteinase. Peptide libraries were used to profile + the substrate specificity of MMP-26 from the P4\u2013P4\u2032 sites. The optimal + cleavage motifs for MMP-26 were Lys-Pro-Ile/Leu-Ser(P1)-Leu/Met(P1\u2032)-Ile/Thr-Ser/Ala-Ser. + The strongest preference was observed at the P1\u2032 and P2 sites where hydrophobic + residues were favored. Proline was preferred at P3, and Serine was preferred + at P1. The overall specificity was similar to that of other MMPs with the + exception that more flexibility was observed at P1, P2\u2032, and P3\u2032. + Accordingly, synthetic inhibitors of gelatinases and collagenases inhibited + MMP-26 with similar efficacy. A pair of stereoisomers had only a 40-fold difference + inK i app values against MMP-26 compared with a 250-fold difference against + neutrophil collagenase, indicating that MMP-26 is less stereoselective for + its inhibitors. MMP-26 autodigested itself during the folding process. Two + of the major autolytic sites were Leu49\u2013Thr50 and Ala75\u2013Leu76, which + still left the cysteine switch sequence (PHC82GVPD) intact. This suggests + that Cys82 may not play a role in the latency of the zymogen. Interestingly, + inhibitor titration studies revealed that only \u223c5% of the total MMP-26 + molecules was catalytically active, indicating that the thiol groups of Cys82 + in the active molecules may be dissociated or removed from the active site + zinc ions. MMP-26 cleaved Phe352\u2013Leu353 and Pro357\u2013Met358 in the + reactive loop of \u03b11-proteinase inhibitor and His140\u2013Val141 in insulin-like + growth factor-binding protein-1, probably rendering these substrates inactive. + Among the fluorescent peptide substrates analyzed, Mca-Pro-Leu-Ala-Nva-Dpa-Ala-Arg-NH2 + displayed the highest specificity constant (30,000/molar second) with MMP-26. + This report proposes a working model for the future studies of pro-MMP-26 + activation, the design of inhibitors, and the identification of optimal physiological + and pathological substrates of MMP-26 in vivo.", "venue": "Journal of Biological + Chemistry", "year": 2002, "referenceCount": 48, "citationCount": 62, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/277/38/35168.full.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2002-09-20", "journal": {"volume": + "277", "pages": "35168 - 35175", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "40163601", "name": "H. Park"}, {"authorId": "25581223", + "name": "B. Turk"}, {"authorId": "15435278", "name": "Ferry E. Gerkema"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "47807700", "name": + "Q. Sang"}]}, {"paperId": "18a9f248d48a73edbac1a1a03ff1abaa83406eb9", "externalIds": + {"MAG": "2078685722", "DOI": "10.1006/SMIM.2001.0337", "CorpusId": 37044612, + "PubMed": "11884226"}, "corpusId": 37044612, "publicationVenue": {"id": "1d2c294f-5435-4adc-84d0-cd6903a42990", + "name": "Seminars in Immunology", "type": "journal", "alternate_names": ["Semin + Immunol"], "issn": "1044-5323", "url": "http://www.clinicalkey.com.au/dura/browse/journalIssue/10445323", + "alternate_urls": ["http://www.idealibrary.com/cgi-bin/links/toc/si", "https://www.journals.elsevier.com/seminars-in-immunology/", + "http://www.clinicalkey.com/dura/browse/journalIssue/10445323", "http://www.sciencedirect.com/science/journal/10445323"]}, + "url": "https://www.semanticscholar.org/paper/18a9f248d48a73edbac1a1a03ff1abaa83406eb9", + "title": "Phosphoinositide 3-kinase in immunological systems.", "abstract": + "Phosphoinositide 3-kinases (PI3Ks) are an evolutionarily conserved family + of signal transducing enzymes. A great variety of stimuli activate PI3K, leading + to the transient accumulation of its lipid products in cell membranes. These + lipids serve as second messengers to regulate the location and activity of + an array of downstream effector molecules. In cells of the mammalian immune + system, PI3K is activated by receptors for antigen, cytokines, costimulatory + molecules, immunoglobulins and chemoattractants. Signaling via PI3K regulates + immune cell proliferation, survival, differentiation, chemotaxis, phagocytosis, + degranulation, and respiratory burst. Here we review our current understanding + of PI3K signaling in leukocytes.", "venue": "Seminars in Immunology", "year": + 2002, "referenceCount": 133, "citationCount": 243, "influentialCitationCount": + 15, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "2002-02-01", "journal": {"volume": "14 1", "pages": "\n 7-18\n ", + "name": "Seminars in immunology"}, "authors": [{"authorId": "6241317", "name": + "D. Fruman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "4b8206b199b5737c7f78020112555f0ab8a658b7", "externalIds": {"MAG": "1967830116", + "DOI": "10.1016/S0003-2697(02)00268-3", "CorpusId": 21594528, "PubMed": "12419351"}, + "corpusId": 21594528, "publicationVenue": {"id": "d0046ca9-9064-464a-ab1f-8947412a4f14", + "name": "Analytical Biochemistry", "type": "journal", "alternate_names": ["Anal + Biochem"], "issn": "0003-2697", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/622781/description#description", + "alternate_urls": ["http://www.journals.elsevier.com/analytical-biochemistry-methods-in-the-biological-sciences/", + "http://www.sciencedirect.com/science/journal/00032697"]}, "url": "https://www.semanticscholar.org/paper/4b8206b199b5737c7f78020112555f0ab8a658b7", + "title": "An integrated vector system for cellular studies of phage display-derived + peptides.", "abstract": null, "venue": "Analytical Biochemistry", "year": + 2002, "referenceCount": 12, "citationCount": 9, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2002-09-15", "journal": {"volume": "308 2", "pages": "\n 364-72\n ", + "name": "Analytical biochemistry"}, "authors": [{"authorId": "2045394", "name": + "S. Voss"}, {"authorId": "14477240", "name": "A. Degrand"}, {"authorId": "1736674926", + "name": "G. Romeo"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1788876", "name": "J. Frangioni"}]}, {"paperId": "4f8058d520e7287725c518740facc77f703d356c", + "externalIds": {"MAG": "2139270233", "DOI": "10.1172/JCI13305", "CorpusId": + 29471107, "PubMed": "11781359"}, "corpusId": 29471107, "publicationVenue": + {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", "name": "Journal of Clinical + Investigation", "type": "journal", "alternate_names": ["J Clin Investig"], + "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": ["http://www.jci.org/", + "https://www.jci.org/archive", "http://www.jci.org/impact"]}, "url": "https://www.semanticscholar.org/paper/4f8058d520e7287725c518740facc77f703d356c", + "title": "Reduced expression of the murine p85alpha subunit of phosphoinositide + 3-kinase improves insulin signaling and ameliorates diabetes.", "abstract": + "A critical component of insulin action is the enzyme phosphoinositide (PI) + 3-kinase. The major regulatory subunits of PI 3-kinase, p85alpha and its splice + variants, are encoded by the Pik3r1 gene. Heterozygous disruption of Pik3r1 + improves insulin signaling and glucose homeostasis in normal mice and mice + made insulin-resistant by heterozygous deletion of the Insulin receptor and/or + insulin receptor substrate-1 (IRS1) genes. Reduced expression of p85 modulates + the molecular balance between this protein, the p110 catalytic subunit of + PI 3-kinase, and the IRS proteins. Thus, despite the decrease in p85alpha, + PI 3-kinase activation is normal, insulin-stimulated Akt activity is increased, + and glucose tolerance and insulin sensitivity are improved. Furthermore, Pik3r1 + heterozygosity protects mice with genetic insulin resistance from developing + diabetes. These data suggest that regulation of p85alpha levels may provide + a novel therapeutic target for the treatment of type 2 diabetes.", "venue": + "Journal of Clinical Investigation", "year": 2002, "referenceCount": 44, "citationCount": + 254, "influentialCitationCount": 8, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jci.org/articles/view/13305/files/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "109 1", "pages": "\n 141-9\n ", + "name": "The Journal of clinical investigation"}, "authors": [{"authorId": + "1396480779", "name": "F. Mauvais-Jarvis"}, {"authorId": "5177377", "name": + "K. Ueki"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "6040440", + "name": "M. Hirshman"}, {"authorId": "152590916", "name": "K. Sakamoto"}, + {"authorId": "5766174", "name": "L. Goodyear"}, {"authorId": "47379953", "name": + "M. Iannacone"}, {"authorId": "4246425", "name": "D. Accili"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": "C. Kahn"}]}, + {"paperId": "50ced3e181cb003698fd6e97743e38ec3ac9c74f", "externalIds": {"MAG": + "2087812126", "DOI": "10.1073/pnas.202476899", "CorpusId": 24561818, "PubMed": + "12271141"}, "corpusId": 24561818, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/50ced3e181cb003698fd6e97743e38ec3ac9c74f", + "title": "Tuberous sclerosis complex-1 and -2 gene products function together + to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling", + "abstract": "Tuberous sclerosis complex (TSC) is an autosomal dominant genetic + disorder that occurs upon mutation of either the TSC1 or TSC2 genes, which + encode the protein products hamartin and tuberin, respectively. Here, we show + that hamartin and tuberin function together to inhibit mammalian target of + rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding + protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). First, coexpression + of hamartin and tuberin repressed phosphorylation of 4E-BP1, resulting in + increased association of 4E-BP1 with eIF4E; importantly, a mutant of TSC2 + derived from TSC patients was defective in repressing phosphorylation of 4E-BP1. + Second, the activity of S6K1 was repressed by coexpression of hamartin and + tuberin, but the activity of rapamycin-resistant mutants of S6K1 were not + affected, implicating mTOR in the TSC-mediated inhibitory effect on S6K1. + Third, hamartin and tuberin blocked the ability of amino acids to activate + S6K1 within nutrient-deprived cells, a process that is dependent on mTOR. + These findings strongly implicate the tuberin-hamartin tumor suppressor complex + as an inhibitor of mTOR and suggest that the formation of tumors within TSC + patients may result from aberrantly high levels of mTOR-mediated signaling + to downstream targets.", "venue": "Proceedings of the National Academy of + Sciences of the United States of America", "year": 2002, "referenceCount": + 31, "citationCount": 815, "influentialCitationCount": 34, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc129715?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2002-09-23", "journal": {"volume": + "99", "pages": "13571 - 13576", "name": "Proceedings of the National Academy + of Sciences of the United States of America"}, "authors": [{"authorId": "3870554", + "name": "A. Tee"}, {"authorId": "6713214", "name": "D. Fingar"}, {"authorId": + "2339651", "name": "B. Manning"}, {"authorId": "2942901", "name": "D. Kwiatkowski"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4037343", "name": + "J. Blenis"}]}, {"paperId": "687b9c3ac404bb2580d763e2bf634b6f1137960b", "externalIds": + {"MAG": "2090715627", "DOI": "10.1126/stke.2002.162.pe49", "CorpusId": 20620012, + "PubMed": "12475999"}, "corpusId": 20620012, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/687b9c3ac404bb2580d763e2bf634b6f1137960b", + "title": "Hitting the Target: Emerging Technologies in the Search for Kinase + Substrates", "abstract": "Through phosphorylation, protein kinases can alter + the activity, localization, protein association, and stability of their targets. + Despite the importance to our understanding of all aspects of cell biology, + progress toward identifying bona fide substrates of specific protein kinases + has been slow. Traditionally used techniques to identify true kinase substrates, + such as genetics, yeast two-hybrid screens, and biochemical purification, + are often laborious and unreliable. However, several new approaches have recently + been developed and used successfully to identify genuine in vivo substrates + of certain protein kinases. These methods include screening for phosphorylation + of proteins from phage expression libraries, peptide library screens to determine + optimal motifs favored by specific kinases, the use of phospho-motif antibodies, + and an approach that uses structurally altered kinases and allele-specific + adenosine triphosphate analogs and kinase inhibitors. We describe these approaches + and discuss their utility and inherent caveats.", "venue": "Science''s STKE", + "year": 2002, "referenceCount": 38, "citationCount": 111, "influentialCitationCount": + 3, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "2002-12-10", "journal": {"volume": "2002", "pages": "pe49 - pe49", "name": + "Science''s STKE"}, "authors": [{"authorId": "2339651", "name": "B. Manning"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "8c23e74cb3f0b27d00b946c82e4f67e90de121c8", + "externalIds": {"MAG": "2133891056", "DOI": "10.1038/ncb811", "CorpusId": + 13038816, "PubMed": "12080346"}, "corpusId": 13038816, "publicationVenue": + {"id": "7d182b83-7d8d-43fb-9fd6-ae67fbafab20", "name": "Nature Cell Biology", + "type": "journal", "alternate_names": ["Nat Cell Biology"], "issn": "1465-7392", + "url": "http://www.nature.com/naturecellbiology", "alternate_urls": ["https://www.nature.com/ncb/"]}, + "url": "https://www.semanticscholar.org/paper/8c23e74cb3f0b27d00b946c82e4f67e90de121c8", + "title": "A PtdInsP3- and Rho GTPase-mediated positive feedback loop regulates + neutrophil polarity", "abstract": null, "venue": "Nature Cell Biology", "year": + 2002, "referenceCount": 29, "citationCount": 541, "influentialCitationCount": + 34, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2823287?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2002-07-01", "journal": {"volume": + "4", "pages": "509-513", "name": "Nature Cell Biology"}, "authors": [{"authorId": + "3528639", "name": "O. Weiner"}, {"authorId": "33510096", "name": "Paul O. + Neilsen"}, {"authorId": "2565299", "name": "G. Prestwich"}, {"authorId": "40294231", + "name": "M. Kirschner"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2324026", "name": "H. Bourne"}]}, {"paperId": "b9358d3593e10c8af9f433e9502a2c34a0662133", + "externalIds": {"MAG": "1964659850", "DOI": "10.1073/pnas.052713899", "CorpusId": + 40838184, "PubMed": "11867762"}, "corpusId": 40838184, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/b9358d3593e10c8af9f433e9502a2c34a0662133", + "title": "Interferon regulatory factor-3 is an in vivo target of DNA-PK", + "abstract": "Eukaryotic cells have evolved complex signaling networks to sense + environmental stress and to repair stress-induced damage. IFN regulatory factor-3 + (IRF-3) is a transcription factor that plays a central role in the host response + to viral infection. Although the main activity of IRF-3 characterized to date + has been its role in the induction of IFN-\u03b1 and -\u03b2 after virus infection, + recent evidence indicates additional roles for IRF-3 in the response to DNA + damage and in virus-induced apoptosis. Here we identify IRF-3 as the first + in vivo target for DNA-dependent protein kinase (DNA-PK). Phosphorylation + of IRF-3 by DNA-PK after virus infection results in its nuclear retention + and delayed proteolysis. These results expand the known roles of DNA-PK and + provide a functional link between the cellular machineries that regulate the + innate immune response and that sense and respond to DNA damage. As such this + study contributes to a more integrated view of the cellular responses to various + cellular stress signals.", "venue": "Proceedings of the National Academy of + Sciences of the United States of America", "year": 2002, "referenceCount": + 33, "citationCount": 126, "influentialCitationCount": 12, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.pnas.org/content/99/5/2818.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2002-02-26", "journal": {"volume": + "99", "pages": "2818 - 2823", "name": "Proceedings of the National Academy + of Sciences of the United States of America"}, "authors": [{"authorId": "36006807", + "name": "A. Karpova"}, {"authorId": "152124389", "name": "M. Trost"}, {"authorId": + "145517618", "name": "J. Murray"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3294583", "name": "P. Howley"}]}, {"paperId": "bc94ab46bf47a79eb2ebc93891fbca46658ad866", + "externalIds": {"MAG": "2070732456", "DOI": "10.1126/SCIENCE.296.5573.1655", + "CorpusId": 25108977, "PubMed": "12040186"}, "corpusId": 25108977, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/bc94ab46bf47a79eb2ebc93891fbca46658ad866", + "title": "The phosphoinositide 3-kinase pathway.", "abstract": "Phosphorylated + lipids are produced at cellular membranes during signaling events and contribute + to the recruitment and activation of various signaling components. The role + of phosphoinositide 3-kinase (PI3K), which catalyzes the production of phosphatidylinositol-3,4,5-trisphosphate, + in cell survival pathways; the regulation of gene expression and cell metabolism; + and cytoskeletal rearrangements are highlighted. The PI3K pathway is implicated + in human diseases including diabetes and cancer, and understanding the intricacies + of this pathway may provide new avenues for therapuetic intervention.", "venue": + "Science", "year": 2002, "referenceCount": 5, "citationCount": 5442, "influentialCitationCount": + 298, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "2002-05-31", "journal": + {"volume": "296 5573", "pages": "\n 1655-7\n ", "name": "Science"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "db091e961df79eba4d8e009a75aa4cb1d69ccc98", + "externalIds": {"MAG": "2129221351", "DOI": "10.1128/MCB.22.3.965-977.2002", + "CorpusId": 33429041, "PubMed": "11784871"}, "corpusId": 33429041, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/db091e961df79eba4d8e009a75aa4cb1d69ccc98", + "title": "Molecular Balance between the Regulatory and Catalytic Subunits + of Phosphoinositide 3-Kinase Regulates Cell Signaling and Survival", "abstract": + "ABSTRACT Class Ia phosphoinositide (PI) 3-kinase is a central component in + growth factor signaling and is comprised of a p110 catalytic subunit and a + regulatory subunit, the most common family of which is derived from the p85\u03b1 + gene (Pik3r1). Optimal signaling through the PI 3-kinase pathway depends on + a critical molecular balance between the regulatory and catalytic subunits. + In wild-type cells, the p85 subunit is more abundant than p110, leading to + competition between the p85 monomer and the p85-p110 dimer and ineffective + signaling. Heterozygous disruption of Pik3r1 results in increased Akt activity + and decreased apoptosis by insulin-like growth factor 1 (IGF-1) through up-regulated + phosphatidylinositol (3,4,5)-triphosphate production. Complete depletion of + p85\u03b1, on the other hand, results in significantly increased apoptosis + due to reduced PI 3-kinase-dependent signaling. Thus, a reduction in p85\u03b1 + represents a novel therapeutic target for enhancing IGF-1/insulin signaling, + prolongation of cell survival, and protection against apoptosis.", "venue": + "Molecular and Cellular Biology", "year": 2002, "referenceCount": 57, "citationCount": + 288, "influentialCitationCount": 14, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc133541?pdf=render", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2002-02-01", "journal": {"volume": "22", "pages": "965 - 977", "name": "Molecular + and Cellular Biology"}, "authors": [{"authorId": "5177377", "name": "K. Ueki"}, + {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "3710358", "name": + "S. Brachmann"}, {"authorId": "87128090", "name": "Y. Tseng"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "144391716", "name": "C. Kahn"}]}, + {"paperId": "ed269fcd6d673ea7773d4762d013cd10467f18b6", "externalIds": {"MAG": + "2171908036", "DOI": "10.1128/MCB.22.8.2799-2809.2002", "CorpusId": 21764354, + "PubMed": "11909972"}, "corpusId": 21764354, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/ed269fcd6d673ea7773d4762d013cd10467f18b6", + "title": "Akt/Protein Kinase B Promotes Organ Growth in Transgenic Mice", + "abstract": "ABSTRACT One of the least-understood areas in biology is the + determination of the size of animals and their organs. In Drosophila, components + of the insulin receptor phosphoinositide 3-kinase (PI3K) pathway determine + body, organ, and cell size. Several biochemical studies have suggested that + Akt/protein kinase B is one of the important downstream targets of PI3K. To + examine the role of Akt in the regulation of organ size in mammals, we have + generated and characterized transgenic mice expressing constitutively active + Akt (caAkt) or kinase-deficient Akt (kdAkt) specifically in the heart. The + heart weight of caAkt transgenic mice was increased 2.0-fold compared with + that of nontransgenic mice. The increase in heart size was associated with + a comparable increase in myocyte cell size in caAkt mice. The kdAkt mutant + protein attenuated the constitutively active PI3K-induced overgrowth of the + heart, and the caAkt mutant protein circumvented cardiac growth retardation + induced by a kinase-deficient PI3K mutant protein. Rapamycin attenuated caAkt-induced + overgrowth of the heart, suggesting that the mammalian target of rapamycin + (mTOR) or effectors of mTOR mediated caAkt-induced heart growth. In conclusion, + Akt is sufficient to induce a marked increase in heart size and is likely + to be one of the effectors of the PI3K pathway in mediating heart growth.", + "venue": "Molecular and Cellular Biology", "year": 2002, "referenceCount": + 83, "citationCount": 528, "influentialCitationCount": 19, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc133704?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2002-04-15", "journal": {"volume": + "22", "pages": "2799 - 2809", "name": "Molecular and Cellular Biology"}, "authors": + [{"authorId": "6946601", "name": "T. Shioi"}, {"authorId": "6688807", "name": + "J. McMullen"}, {"authorId": "2302010", "name": "P. Kang"}, {"authorId": "1995988", + "name": "P. Douglas"}, {"authorId": "3091430", "name": "T. Obata"}, {"authorId": + "50377077", "name": "T. Franke"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "47072554", "name": "S. Izumo"}]}, {"paperId": "ee8682f38a69a649d631641f427778581e88bd67", + "externalIds": {"MAG": "1992999254", "DOI": "10.1016/S1534-5807(02)00150-8", + "CorpusId": 27188319, "PubMed": "11970891"}, "corpusId": 27188319, "publicationVenue": + {"id": "744d2ff9-76f1-4f43-be2a-45775418e1a2", "name": "Developmental Cell", + "type": "journal", "alternate_names": ["Dev Cell"], "issn": "1534-5807", "url": + "https://www.cell.com/developmental-cell/home", "alternate_urls": ["http://www.sciencedirect.com/science/journal/15345807", + "http://www.developmentalcell.com/"]}, "url": "https://www.semanticscholar.org/paper/ee8682f38a69a649d631641f427778581e88bd67", + "title": "Lipid research picks up speed on the slopes of Taos.", "abstract": + null, "venue": "Developmental Cell", "year": 2002, "referenceCount": 12, "citationCount": + 3, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": {"url": + "http://www.cell.com/article/S1534580702001508/pdf", "status": null}, "fieldsOfStudy": + ["Biology", "Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Chemistry", "source": "external"}, {"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review"], "publicationDate": "2002-04-01", "journal": + {"volume": "2 4", "pages": "\n 407-10\n ", "name": "Developmental + cell"}, "authors": [{"authorId": "123039768", "name": "S. Field"}, {"authorId": + "5493258", "name": "K. Lamia"}, {"authorId": "4109960", "name": "L. Rameh"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "f060372cd7c9c05c58b12cfdb817efaa651ebbfe", + "externalIds": {"MAG": "2094941511", "DOI": "10.1016/S1097-2765(02)00568-3", + "CorpusId": 14936921, "PubMed": "12150915"}, "corpusId": 14936921, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/f060372cd7c9c05c58b12cfdb817efaa651ebbfe", + "title": "Identification of the tuberous sclerosis complex-2 tumor suppressor + gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway.", + "abstract": null, "venue": "Molecules and Cells", "year": 2002, "referenceCount": + 109, "citationCount": 1531, "influentialCitationCount": 118, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276502005683/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2002-07-01", "journal": {"volume": + "10 1", "pages": "\n 151-62\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "2339651", "name": "B. Manning"}, {"authorId": "3870554", + "name": "A. Tee"}, {"authorId": "143800250", "name": "M. Logsdon"}, {"authorId": + "4037343", "name": "J. Blenis"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "05fcaec1bc344b4e2ebfcb0841da85d9d5208f28", "externalIds": {"MAG": + "2157917051", "DOI": "10.1074/JBC.M011414200", "CorpusId": 25722761, "PubMed": + "11278902"}, "corpusId": 25722761, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/05fcaec1bc344b4e2ebfcb0841da85d9d5208f28", + "title": "Marked Differences between Metalloproteases Meprin A and B in Substrate + and Peptide Bond Specificity*", "abstract": "Meprin A and B are highly regulated, + secreted, and cell-surface metalloendopeptidases that are abundantly expressed + in the kidney and intestine. Meprin oligomers consist of evolutionarily related + \u03b1 and/or \u03b2 subunits. The work herein was carried out to identify + bioactive peptides and proteins that are susceptible to hydrolysis by mouse + meprins and kinetically characterize the hydrolysis. Gastrin-releasing peptide + fragment 14\u201327 and gastrin 17, regulatory molecules of the gastrointestinal + tract, were found to be the best peptide substrates for meprin A and B, respectively. + Peptide libraries and a variety of naturally occurring peptides revealed that + the meprin \u03b2 subunit has a clear preference for acidic amino acids in + the P1 and P1\u2032 sites of substrates. The meprin \u03b1 subunit selected + for small (e.g. serine, alanine) or hydrophobic (e.g. phenylalanine) residues + in the P1 and P1\u2032 sites, and proline was the most preferred amino acid + at the P2\u2032 position. Thus, although the meprin \u03b1 and \u03b2 subunits + share 55% amino acid identity within the protease domain and are normally + localized at the same tissue cell surfaces, they have very different substrate + and peptide bond specificities indicating different functions. Homology models + of the mouse meprin \u03b1 and \u03b2 protease domains, based on the astacin + crystal structure, revealed active site differences that can account for the + marked differences in substrate specificity of the two subunits.", "venue": + "Journal of Biological Chemistry", "year": 2001, "referenceCount": 39, "citationCount": + 117, "influentialCitationCount": 4, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], + "publicationDate": "2001-04-20", "journal": {"volume": "276", "pages": "13248 + - 13255", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "5838666", "name": "G. Bertenshaw"}, {"authorId": "25581223", "name": "B. + Turk"}, {"authorId": "145830304", "name": "S. Hubbard"}, {"authorId": "6524877", + "name": "G. Matters"}, {"authorId": "4051561", "name": "J. Bylander"}, {"authorId": + "34392859", "name": "J. Crisman"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "13210436", "name": "J. Bond"}]}, {"paperId": "16d16c6437f908b9889e107be6f6f661cbabbded", + "externalIds": {"MAG": "1787971046", "DOI": "10.4049/jimmunol.167.8.4553", + "CorpusId": 46044630, "PubMed": "11591783"}, "corpusId": 46044630, "publicationVenue": + {"id": "3456d2d7-a9b4-495f-a7a0-a238096ee07a", "name": "Journal of Immunology", + "type": "journal", "alternate_names": ["J Immunol"], "issn": "0022-1767", + "url": "https://www.jimmunol.org/", "alternate_urls": ["http://www.jimmunol.org/"]}, + "url": "https://www.semanticscholar.org/paper/16d16c6437f908b9889e107be6f6f661cbabbded", + "title": "Phosphatidylinositol 3-Kinase Confers Resistance to Encephalomyocarditis + and Herpes Simplex Virus-Induced Cell Death Through the Activation of Distinct + Downstream Effectors1", "abstract": "The Janus kinase/STAT pathway has emerged + as the paradigm of IFN-induced protection from viral infections. However, + the possible participation of other signaling proteins in this protection + is not clearly understood. In this report, we demonstrate that activation + of phosphatidylinositol 3-kinase (PI3K) by either serum factors or IFNs blocks + cell death induced by encephalomyocarditis virus (EMCV) and HSV. This increased + resistance to virus-induced cell death does not involve the activation of + the STAT pathway and occurs in the presence of normal viral replication. Interestingly, + the cell uses two different PI3K regulated pathways to block EMCV- and HSV-induced + cell death. The increased sensitivity of p85\u03b1\u2212/\u2212 embryonic + fibroblasts to EMCV-induced cell death is specifically corrected by overexpression + of an activated allele of Akt/protein kinase B, but not activated mitogen-activated + protein kinase extracellular kinase. Conversely, the augmented sensitivity + of p85\u03b1\u2212/\u2212 cells to HSV-induced cell death was compensated + for by expression of an activated form of mitogen-activated protein kinase + extracellular kinase, but not by activated Akt/protein kinase B. We conclude + from these data that PI3K-activated pathways function in parallel with the + Janus kinase/STAT pathway to protect cells from the lethal effects of viruses.", + "venue": "Journal of Immunology", "year": 2001, "referenceCount": 49, "citationCount": + 20, "influentialCitationCount": 0, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.jimmunol.org/content/jimmunol/167/8/4553.full.pdf", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2001-10-15", "journal": {"volume": "167", "pages": "4553 + - 4559", "name": "The Journal of Immunology"}, "authors": [{"authorId": "49918065", + "name": "C. Prejean"}, {"authorId": "39939310", "name": "T. Sarma"}, {"authorId": + "6048665", "name": "O. Kurnasov"}, {"authorId": "8986504", "name": "A. Usacheva"}, + {"authorId": "2384507", "name": "B. Hemmings"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "31973366", "name": "L. Morrison"}, {"authorId": "143637244", "name": "R. + Buller"}, {"authorId": "6324275", "name": "O. Colamonici"}]}, {"paperId": + "27a932e4e03c4cb58c91c305478a9d82368c80f3", "externalIds": {"CorpusId": 14591803}, + "corpusId": 14591803, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/27a932e4e03c4cb58c91c305478a9d82368c80f3", + "title": "Downstream Effectors Through the Activation of Distinct Herpes Simplex + Virus-Induced Cell Death Resistance to Encephalomyocarditis and Phosphatidylinositol + 3-Kinase Confers", "abstract": null, "venue": "", "year": 2001, "referenceCount": + 45, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": null, "authors": [{"authorId": "49918065", "name": "C. Prejean"}, + {"authorId": "39939310", "name": "T. Sarma"}, {"authorId": "6048665", "name": + "O. Kurnasov"}, {"authorId": "8986504", "name": "A. Usacheva"}, {"authorId": + "2384507", "name": "B. Hemmings"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "31973366", "name": + "L. Morrison"}, {"authorId": "143637244", "name": "R. Buller"}, {"authorId": + "6324275", "name": "O. Colamonici"}]}, {"paperId": "45cc15f59fdf15bdeda88a8cbe53a835671ebfce", + "externalIds": {"MAG": "2118469376", "DOI": "10.1073/pnas.012581799", "CorpusId": + 30402101, "PubMed": "11752399"}, "corpusId": 30402101, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/45cc15f59fdf15bdeda88a8cbe53a835671ebfce", + "title": "Increased insulin sensitivity in mice lacking p85\u03b2 subunit + of phosphoinositide 3-kinase", "abstract": "On the basis of ex vivo studies + using insulin-responsive cells, activation of a Class IA phosphoinositide + 3-kinase (PI3K) seems to be required for a wide variety of cellular responses + downstream of insulin. The Class IA PI3K enzymes are heterodimers of catalytic + and regulatory subunits. In mammals, insulin-responsive tissues express both + the p85\u03b1 and p85\u03b2 isoforms of the regulatory subunit. Surprisingly, + recent studies have revealed that disruption of the p85\u03b1 gene in the + mouse (p85\u03b1\u2212/\u2212 mice) results in hypoglycemia with decreased + plasma insulin, and the p85\u03b1+/\u2212 mice exhibit significantly increased + insulin sensitivity. These results suggest either that p85\u03b1 negatively + regulates insulin signaling, or that p85\u03b2, which mediates the major fraction + of Class IA PI3K signaling in the absence of p85\u03b1, is more efficient + than p85\u03b1 in mediating insulin responses. To address this question, we + have generated mice in which the p85\u03b2 gene is deleted (p85\u03b2\u2212/\u2212 + mice). As with the p85\u03b1\u2212/\u2212 mice, the p85\u03b2\u2212/\u2212 + mice showed hypoinsulinemia, hypoglycemia, and improved insulin sensitivity. + At the molecular level, PI3K activity associated with phosphotyrosine complexes + was preserved despite a 20\u201330% reduction in the total protein level of + the regulatory subunits. Moreover, insulin-induced activation of AKT was significantly + up-regulated in muscle from the p85\u03b2\u2212/\u2212 mice. In addition, + insulin-dependent tyrosine phosphorylation of insulin receptor substrate-2 + was enhanced in the p85\u03b2\u2212/\u2212 mice, a phenotype not observed + in the p85\u03b1\u2212/\u2212 mice. These results indicate that in addition + to their roles in recruiting the catalytic subunit of PI3K to the insulin + receptor substrate proteins, both p85\u03b1 and p85\u03b2 play negative roles + in insulin signaling.", "venue": "Proceedings of the National Academy of Sciences + of the United States of America", "year": 2001, "referenceCount": 38, "citationCount": + 254, "influentialCitationCount": 10, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc117575?pdf=render", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Medicine", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2001-12-18", "journal": + {"volume": "99", "pages": "419 - 424", "name": "Proceedings of the National + Academy of Sciences of the United States of America"}, "authors": [{"authorId": + "5177377", "name": "K. Ueki"}, {"authorId": "7777071", "name": "C. Yballe"}, + {"authorId": "3710358", "name": "S. Brachmann"}, {"authorId": "9928532", "name": + "D. Vicent"}, {"authorId": "40474206", "name": "J. Watt"}, {"authorId": "144391716", + "name": "C. Kahn"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "7d1a6ed048fc0bb7462b0625ab3e254a2389e0dc", "externalIds": {"CorpusId": 252035666}, + "corpusId": 252035666, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7d1a6ed048fc0bb7462b0625ab3e254a2389e0dc", + "title": "Differential Immediate Early Gene Expression Induced by", "abstract": + "Department of Cell Biology, Harvard Medical School and Division of Signal + Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215 Present + address: Department of Biological Chemistry and UC Davis Cancer Center, University + of California at Davis, Sacramento, CA 95817 Whitehead Institute for Biomedical + Research, Nine Cambridge Center, Cambridge, MA 02142 Present address: Oxford + Bioscience Partners, 315 Post Road West, Westport, CT 06880 Department of + Biology, Massachusetts Institute of Technology, Cambridge, MA 02139", "venue": + "", "year": 2001, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "40187510", + "name": "C. Sweeney"}, {"authorId": "5271873", "name": "D. Fambrough"}, {"authorId": + "5899757", "name": "C. Huard"}, {"authorId": "48917515", "name": "A. Diamonti"}, + {"authorId": "89333493", "name": "S. Eric"}, {"authorId": "2094986476", "name": + "Lander"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145331905", + "name": "K. Carraway"}]}, {"paperId": "82e23963895661958ecbb80f43c651a88ebe3d86", + "externalIds": {"MAG": "2170516740", "DOI": "10.1172/JCI12874", "CorpusId": + 33120473, "PubMed": "11696584"}, "corpusId": 33120473, "publicationVenue": + {"id": "8c9a9e1b-acf2-4274-8d73-6ea0ecd11fd1", "name": "Journal of Clinical + Investigation", "type": "journal", "alternate_names": ["J Clin Investig"], + "issn": "0021-9738", "url": "https://www.jci.org/", "alternate_urls": ["http://www.jci.org/", + "https://www.jci.org/archive", "http://www.jci.org/impact"]}, "url": "https://www.semanticscholar.org/paper/82e23963895661958ecbb80f43c651a88ebe3d86", + "title": "Phosphatidylinositol 3-kinase-dependent activation of trypsinogen + modulates the severity of acute pancreatitis.", "abstract": "Intra-acinar + cell activation of digestive enzyme zymogens including trypsinogen is generally + believed to be an early and critical event in acute pancreatitis. We have + found that the phosphatidylinositol 3-kinase inhibitor wortmannin can reduce + the intrapancreatic activation of trypsinogen that occurs during two dissimilar + experimental models of rodent acute pancreatitis, secretagogue- and duct injection-induced + pancreatitis. The severity of both models was also reduced by wortmannin administration. + In contrast, the NF-kappa B activation that occurs during the early stages + of secretagogue-induced pancreatitis is not altered by administration of wortmannin. + Ex vivo, caerulein-induced trypsinogen activation is inhibited by wortmannin + and LY294002. However, the cytoskeletal changes induced by caerulein were + not affected by wortmannin. Concentrations of caerulein that induced ex vivo + trypsinogen activation do not significantly increase phosphatidylinositol-3,4-bisphosphate + or phosphatidylinositol 3,4,5-trisphosphate levels or induce phosphorylation + of Akt/PKB, suggesting that class I phosphatidylinositol 3-kinases are not + involved. The concentration of wortmannin that inhibits trypsinogen activation + causes a 75% decrease in phosphatidylinositol 3-phosphate, which is implicated + in vesicle trafficking and fusion. We conclude that a wortmannin-inhibitable + phosphatidylinositol 3-kinase is necessary for intrapancreatic activation + of trypsinogen and regulating the severity of acute pancreatitis. Our observations + suggest that phosphatidylinositol 3-kinase inhibition might be of benefit + in preventing acute pancreatitis.", "venue": "Journal of Clinical Investigation", + "year": 2001, "referenceCount": 35, "citationCount": 120, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jci.org/articles/view/12874/files/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2001-11-01", "journal": {"volume": + "108 9", "pages": "\n 1387-95\n ", "name": "The Journal of + clinical investigation"}, "authors": [{"authorId": "2118126354", "name": "V. + P. Singh"}, {"authorId": "3243764", "name": "A. Saluja"}, {"authorId": "4197684", + "name": "L. Bhagat"}, {"authorId": "50265861", "name": "G. V. van Acker"}, + {"authorId": "32459743", "name": "A. Song"}, {"authorId": "4324390", "name": + "S. Soltoff"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2840737", "name": "M. Steer"}]}, {"paperId": "95a5e7d238d2f998b983a19a6f3c2ee17034a244", + "externalIds": {"PubMedCentral": "2150784", "MAG": "2104467943", "DOI": "10.1083/jcb.200107069", + "CorpusId": 3336237, "PubMed": "11581283"}, "corpusId": 3336237, "publicationVenue": + {"id": "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/95a5e7d238d2f998b983a19a6f3c2ee17034a244", + "title": "Distinct roles of class I and class III phosphatidylinositol 3-kinases + in phagosome formation and maturation", "abstract": "Phagosomes acquire their + microbicidal properties by fusion with lysosomes. Products of phosphatidylinositol + 3-kinase (PI 3-kinase) are required for phagosome formation, but their role + in maturation is unknown. Using chimeric fluorescent proteins encoding tandem + FYVE domains, we found that phosphatidylinositol 3-phosphate (PI[3]P) accumulates + greatly but transiently on the phagosomal membrane. Unlike the 3\u2032-phosphoinositides + generated by class I PI 3-kinases which are evident in the nascent phagosomal + cup, PI(3)P is only detectable after the phagosome has sealed. The class III + PI 3-kinase VPS34 was found to be responsible for PI(3)P synthesis and essential + for phagolysosome formation. In contrast, selective ablation of class I PI + 3-kinase revealed that optimal phagocytosis, but not maturation, requires + this type of enzyme. These results highlight the differential functional role + of the two families of kinases, and raise the possibility that PI(3)P production + by VPS34 may be targeted during the maturation arrest induced by some intracellular + parasites.", "venue": "Journal of Cell Biology", "year": 2001, "referenceCount": + 26, "citationCount": 529, "influentialCitationCount": 32, "isOpenAccess": + true, "openAccessPdf": {"url": "https://rupress.org/jcb/article-pdf/155/1/19/1300581/jcb155119.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2001-10-01", "journal": {"volume": + "155", "pages": "19 - 26", "name": "The Journal of Cell Biology"}, "authors": + [{"authorId": "4383992", "name": "O. Vieira"}, {"authorId": "16066763", "name": + "R. Botelho"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": "3710358", + "name": "S. Brachmann"}, {"authorId": "92795093", "name": "T. Matsuo"}, {"authorId": + "40343004", "name": "H. Davidson"}, {"authorId": "36178153", "name": "A. Schreiber"}, + {"authorId": "35244019", "name": "J. Backer"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6104144", "name": "S. Grinstein"}]}, {"paperId": + "a4bd3fa1f9d47b52800894f2a3cbce8e3e7d0043", "externalIds": {"MAG": "2123558789", + "DOI": "10.1016/S1097-2765(01)00258-1", "CorpusId": 33675567, "PubMed": "11430832"}, + "corpusId": 33675567, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/a4bd3fa1f9d47b52800894f2a3cbce8e3e7d0043", + "title": "The Peutz-Jegher gene product LKB1 is a mediator of p53-dependent + cell death.", "abstract": null, "venue": "Molecules and Cells", "year": 2001, + "referenceCount": 37, "citationCount": 329, "influentialCitationCount": 19, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276501002581/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2001-06-01", "journal": {"volume": + "7 6", "pages": "\n 1307-19\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "6519399", "name": "P. Karuman"}, {"authorId": "6896988", + "name": "O. Gozani"}, {"authorId": "4798074", "name": "R. Odze"}, {"authorId": + "2116444919", "name": "X. C. Zhou"}, {"authorId": "2107305476", "name": "H. + Zhu"}, {"authorId": "2060344285", "name": "R. Shaw"}, {"authorId": "25598868", + "name": "T. Brien"}, {"authorId": "47760928", "name": "C. D. Bozzuto"}, {"authorId": + "21764505", "name": "D. Ooi"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2107677136", "name": "J. Yuan"}]}, {"paperId": "aa0f9a9da2077c7b3ff472308d68abac5a75733b", + "externalIds": {"MAG": "2074058888", "DOI": "10.1038/nbt1201-1148", "CorpusId": + 485155, "PubMed": "11731784"}, "corpusId": 485155, "publicationVenue": {"id": + "458166b3-de17-4bf3-bbbb-e53782de2f0f", "name": "Nature Biotechnology", "type": + "journal", "alternate_names": ["Nat Biotechnol"], "issn": "1087-0156", "url": + "http://www.nature.com/nbt/", "alternate_urls": ["http://www.nature.com/nbt"]}, + "url": "https://www.semanticscholar.org/paper/aa0f9a9da2077c7b3ff472308d68abac5a75733b", + "title": "In vivo near-infrared fluorescence imaging of osteoblastic activity", + "abstract": null, "venue": "Nature Biotechnology", "year": 2001, "referenceCount": + 38, "citationCount": 350, "influentialCitationCount": 4, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2001-12-01", "journal": + {"volume": "19", "pages": "1148-1154", "name": "Nature Biotechnology"}, "authors": + [{"authorId": "2571809", "name": "A. Zaheer"}, {"authorId": "2177723", "name": + "R. Lenkinski"}, {"authorId": "39119051", "name": "A. Mahmood"}, {"authorId": + "3084194", "name": "Alun G. Jones"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "1788876", "name": "J. Frangioni"}]}, {"paperId": "aad734bd4a3d0ce98a4f5ce204b9d9e837fdb64a", + "externalIds": {"MAG": "1991336236", "DOI": "10.1126/SCIENCE.1062796", "CorpusId": + 42509408, "PubMed": "11408644"}, "corpusId": 42509408, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/aad734bd4a3d0ce98a4f5ce204b9d9e837fdb64a", + "title": "Translocating Tubby", "abstract": null, "venue": "Science", "year": + 2001, "referenceCount": 0, "citationCount": 16, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}], "publicationTypes": ["JournalArticle", + "LettersAndComments"], "publicationDate": "2001-06-15", "journal": {"volume": + "292", "pages": "2019 - 2021", "name": "Science"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "b0e46f5ce2e84cefbcacad5627c811341570443a", + "externalIds": {"MAG": "1517631297", "DOI": "10.1038/35083070", "CorpusId": + 32649658, "PubMed": "11433300"}, "corpusId": 32649658, "publicationVenue": + {"id": "7d182b83-7d8d-43fb-9fd6-ae67fbafab20", "name": "Nature Cell Biology", + "type": "journal", "alternate_names": ["Nat Cell Biology"], "issn": "1465-7392", + "url": "http://www.nature.com/naturecellbiology", "alternate_urls": ["https://www.nature.com/ncb/"]}, + "url": "https://www.semanticscholar.org/paper/b0e46f5ce2e84cefbcacad5627c811341570443a", + "title": "The PX domains of p47phox and p40phox bind to lipid products of + PI(3)K", "abstract": null, "venue": "Nature Cell Biology", "year": 2001, "referenceCount": + 31, "citationCount": 615, "influentialCitationCount": 45, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2001-07-01", "journal": {"volume": + "3", "pages": "675-678", "name": "Nature Cell Biology"}, "authors": [{"authorId": + "36196723", "name": "F. Kanai"}, {"authorId": "2146672868", "name": "Hui Liu"}, + {"authorId": "123039768", "name": "S. Field"}, {"authorId": "2084848622", + "name": "Hares Akbary"}, {"authorId": "92795093", "name": "T. Matsuo"}, {"authorId": + "2219979", "name": "G. Brown"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "88402408", "name": "M. Yaffe"}]}, {"paperId": "c4f1e5a8fb5ad48b7bbaa08d39b770eb785eebad", + "externalIds": {"MAG": "1555862556", "DOI": "10.1038/90273", "CorpusId": 13510196, + "PubMed": "11433279"}, "corpusId": 13510196, "publicationVenue": {"id": "458166b3-de17-4bf3-bbbb-e53782de2f0f", + "name": "Nature Biotechnology", "type": "journal", "alternate_names": ["Nat + Biotechnol"], "issn": "1087-0156", "url": "http://www.nature.com/nbt/", "alternate_urls": + ["http://www.nature.com/nbt"]}, "url": "https://www.semanticscholar.org/paper/c4f1e5a8fb5ad48b7bbaa08d39b770eb785eebad", + "title": "Determination of protease cleavage site motifs using mixture-based + oriented peptide libraries", "abstract": null, "venue": "Nature Biotechnology", + "year": 2001, "referenceCount": 44, "citationCount": 517, "influentialCitationCount": + 28, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2001-07-01", "journal": {"volume": "19", "pages": "661-667", "name": "Nature + Biotechnology"}, "authors": [{"authorId": "25581223", "name": "B. Turk"}, + {"authorId": "2111011719", "name": "Lisa L. Huang"}, {"authorId": "2071966448", + "name": "Elizabeth T. Piro"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "ced21c9721e29e64a24edc1977523ddbd39b21e7", "externalIds": {"MAG": + "1493799579", "DOI": "10.1038/86737", "CorpusId": 22637369, "PubMed": "11283593"}, + "corpusId": 22637369, "publicationVenue": {"id": "458166b3-de17-4bf3-bbbb-e53782de2f0f", + "name": "Nature Biotechnology", "type": "journal", "alternate_names": ["Nat + Biotechnol"], "issn": "1087-0156", "url": "http://www.nature.com/nbt/", "alternate_urls": + ["http://www.nature.com/nbt"]}, "url": "https://www.semanticscholar.org/paper/ced21c9721e29e64a24edc1977523ddbd39b21e7", + "title": "A motif-based profile scanning approach for genome-wide prediction + of signaling pathways", "abstract": null, "venue": "Nature Biotechnology", + "year": 2001, "referenceCount": 36, "citationCount": 548, "influentialCitationCount": + 27, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2001-04-01", "journal": {"volume": "19", "pages": "348-353", "name": "Nature + Biotechnology"}, "authors": [{"authorId": "88402408", "name": "M. Yaffe"}, + {"authorId": "39756254", "name": "G. Leparc"}, {"authorId": "5000276", "name": + "J. Lai"}, {"authorId": "3091430", "name": "T. Obata"}, {"authorId": "1906416", + "name": "S. Volinia"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d274f406bc47cc21a414b96100c92e29c5984bba", "externalIds": {"MAG": "2148997157", + "DOI": "10.1074/JBC.M100602200", "CorpusId": 22572629, "PubMed": "11297548"}, + "corpusId": 22572629, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/d274f406bc47cc21a414b96100c92e29c5984bba", + "title": "Growth Factor-specific Signaling Pathway Stimulation and Gene Expression + Mediated by ErbB Receptors* 210", "abstract": "The mechanisms by which receptor + tyrosine kinases (RTKs) utilize intracellular signaling pathways to direct + gene expression and cellular response remain unclear. A current question is + whether different RTKs within a single cell target similar or different sets + of genes. In this study we have used the ErbB receptor network to explore + the relationship between RTK activation and gene expression. We profiled growth + factor-stimulated signaling pathway usage and broad gene expression patterns + in two human mammary tumor cell lines expressing different complements of + ErbB receptors. Although the growth factors epidermal growth factor (EGF) + and neuregulin (NRG) 1 similarly stimulated Erk1/2 in MDA-MB-361 cells, EGF + acting through an EGF receptor/ErbB2 heterodimer preferentially stimulated + protein kinase C, and NRG1\u03b2 acting through an ErbB2/ErbB3 heterodimer + preferentially stimulated Akt. The two growth factors regulated partially + overlapping yet distinct sets of genes in these cells. In MDA-MB-453 cells, + NRG1\u03b2 acting through an ErbB2/ErbB3 heterodimer stimulated prolonged + signaling of all pathways examined relative to NRG2\u03b2 acting through the + same heterodimeric receptor species. Surprisingly, NRG1\u03b2 and NRG2\u03b2 + also regulated partially overlapping but distinct sets of genes in these cells. + These results demonstrate that the activation of different RTKs, or activation + of the same RTKs with different ligands, can lead to distinct profiles of + gene regulation within a single cell type. Our observations also suggest that + the identity and kinetics of signaling pathway usage by RTKs may play a role + in the selection of regulated genes.", "venue": "Journal of Biological Chemistry", + "year": 2001, "referenceCount": 58, "citationCount": 132, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/276/25/22685.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2001-06-22", "journal": {"volume": + "276", "pages": "22685 - 22698", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "40187510", "name": "C. Sweeney"}, {"authorId": "5271873", + "name": "D. Fambrough"}, {"authorId": "5899757", "name": "C. Huard"}, {"authorId": + "48917515", "name": "A. Diamonti"}, {"authorId": "9311320", "name": "E. Lander"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145331905", "name": + "K. Carraway"}]}, {"paperId": "030678b47521ce0566887c331dd02fc2f8e1a88f", + "externalIds": {"MAG": "1567219202", "DOI": "10.1038/81715", "CorpusId": 8376820, + "PubMed": "11062485"}, "corpusId": 8376820, "publicationVenue": {"id": "bb27e645-e57c-42c3-bcbc-c7b443c58209", + "name": "Nature Genetics", "type": "journal", "alternate_names": ["Nat Genet"], + "issn": "1061-4036", "url": "http://www.nature.com/ng/", "alternate_urls": + ["http://www.nature.com/ng/index.html"]}, "url": "https://www.semanticscholar.org/paper/030678b47521ce0566887c331dd02fc2f8e1a88f", + "title": "Hypoglycaemia, liver necrosis and perinatal death in mice lacking + all isoforms of phosphoinositide 3-kinase p85\u03b1", "abstract": null, "venue": + "Nature Genetics", "year": 2000, "referenceCount": 32, "citationCount": 311, + "influentialCitationCount": 8, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2000-11-01", "journal": {"volume": "26", "pages": "379-382", "name": "Nature + Genetics"}, "authors": [{"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "1396480779", "name": "F. Mauvais-Jarvis"}, {"authorId": "3055031", "name": + "Daniel A. Pollard"}, {"authorId": "7777071", "name": "C. Yballe"}, {"authorId": + "5592218", "name": "D. Brazil"}, {"authorId": "40803408", "name": "R. Bronson"}, + {"authorId": "144391716", "name": "C. Kahn"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "037b7f4432f45323733731eb9b9b86d25ab38d7e", "externalIds": + {"CorpusId": 1805846, "PubMed": "10681597"}, "corpusId": 1805846, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/037b7f4432f45323733731eb9b9b86d25ab38d7e", + "title": "Impaired kit- but not FcepsilonRI-initiated mast cell activation + in the absence of phosphoinositide 3-kinase p85alpha gene products.", "abstract": + "The class I(A) phosphoinositide 3-kinases (PI3Ks) consist of a 110-kDa catalytic + domain and a regulatory subunit encoded by the p85alpha, p85beta, or p55gamma + genes. We have determined the effects of disrupting the p85alpha gene on the + responses of mast cells stimulated by the cross-linking of Kit and FcepsilonRI, + receptors that reflect innate and adaptive responses, respectively. The absence + of p85alpha gene products partially inhibited Kit ligand/stem cell factor-induced + secretory granule exocytosis, proliferation, and phosphorylation of the serine/threonine + kinase Akt. In contrast, p85alpha gene products were not required for FcepsilonRI-initiated + exocytosis and phosphorylation of Akt. LY294002, which inhibits all classes + of PI3Ks, strongly suppressed Kit- and FcepsilonRI-induced responses in p85alpha + -/- mast cells, revealing the contribution of another PI3K family member(s). + In contrast to B lymphocytes, mast cell proliferation was not dependent on + Bruton''s tyrosine kinase, a downstream effector of PI3K, revealing a distinct + pathway of PI3K-dependent proliferation in mast cells. Our findings represent + the first example of receptor-specific usage of different PI3K family members + in a single cell type. In addition, because Kit- but not FcepsilonRI-initiated + signaling is associated with mast cell proliferation, the results provide + evidence that distinct biologic functions signaled by these two receptors + may reflect differential usage of PI3Ks.", "venue": "Journal of Biological + Chemistry", "year": 2000, "referenceCount": 0, "citationCount": 35, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "275 8", "pages": "\n 6022-9\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "1403245024", + "name": "J. Lu-Kuo"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": + "88707799", "name": "D. M. Joyal"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3648966", "name": "H. Katz"}]}, {"paperId": "1150af2454a992b78864391dee8e4bd57e766fac", + "externalIds": {"MAG": "11510632", "DOI": "10.1038/35036447", "CorpusId": + 511112, "PubMed": "11025682"}, "corpusId": 511112, "publicationVenue": {"id": + "7d182b83-7d8d-43fb-9fd6-ae67fbafab20", "name": "Nature Cell Biology", "type": + "journal", "alternate_names": ["Nat Cell Biology"], "issn": "1465-7392", "url": + "http://www.nature.com/naturecellbiology", "alternate_urls": ["https://www.nature.com/ncb/"]}, + "url": "https://www.semanticscholar.org/paper/1150af2454a992b78864391dee8e4bd57e766fac", + "title": "Phosphoinositide biology \u2013 messages from lipids", "abstract": + null, "venue": "Nature Cell Biology", "year": 2000, "referenceCount": 0, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2000-10-01", "journal": {"volume": "2", "pages": "E190-E190", + "name": "Nature Cell Biology"}, "authors": [{"authorId": "145954100", "name": + "Ji Luo"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "18d826bf92792aca513ee4adc120452d781808ce", + "externalIds": {"MAG": "2016125507", "DOI": "10.1074/JBC.C901015199", "CorpusId": + 11445441, "PubMed": "10867024"}, "corpusId": 11445441, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/18d826bf92792aca513ee4adc120452d781808ce", + "title": "Ligand Discrimination in Signaling through an ErbB4 Receptor Homodimer*", + "abstract": "The epidermal growth factor (EGF)-like family of growth factors + elicits cellular responses by stimulating the dimerization, autophosphorylation, + and tyrosine kinase activities of the ErbB family of receptor tyrosine kinases. + Although several different EGF-like ligands are capable of binding to a single + ErbB family member, it is generally thought that the biological and biochemical + responses of a single receptor dimer to different ligands are indistinguishable. + To test whether an ErbB receptor dimer is capable of discriminating among + ligands we have examined the effect of four EGF-like growth factors on signaling + through the ErbB4 receptor homodimer in CEM/HER4 cells, a transfected human + T cell line ectopically expressing ErbB4 in an ErbB-null background. Despite + stimulating similar levels of gross receptor tyrosine phosphorylation, the + EGF-like growth factors betacellulin, neuregulin-1\u03b2, neuregulin-2\u03b2, + and neuregulin-3 exhibited different biological potencies in a cellular growth + assay. Moreover, the different ligands induced different patterns of recruitment + of intracellular signaling proteins to the activated receptor and induced + differential usage of intracellular kinase signaling cascades. Finally, two-dimensional + phosphopeptide mapping of ligand-stimulated ErbB4 revealed that the different + growth factors induce different patterns of receptor tyrosine phosphorylation. + These results indicate that ErbB4 activation by growth factors is not generic + and suggest that individual ErbB receptors can discriminate between different + EGF-like ligands within the context of a single receptor dimer. More generally, + our observations significantly modify our understanding of signaling through + receptor tyrosine kinases and point to a number of possible models for ligand-mediated + signal diversification.", "venue": "Journal of Biological Chemistry", "year": + 2000, "referenceCount": 32, "citationCount": 119, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/275/26/19803.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2000-06-30", "journal": {"volume": + "275", "pages": "19803 - 19807", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "40187510", "name": "C. Sweeney"}, {"authorId": "2148764882", + "name": "Cary Lai"}, {"authorId": "3631746", "name": "D. Riese"}, {"authorId": + "48917515", "name": "A. Diamonti"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "145331905", "name": "K. Carraway"}]}, {"paperId": "229f933300200d94e6a5417f89e3dcdeb50fa3ac", + "externalIds": {"MAG": "2502174291", "DOI": "10.1385/1-59259-218-X:247", "CorpusId": + 88991620}, "corpusId": 88991620, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/229f933300200d94e6a5417f89e3dcdeb50fa3ac", + "title": "PI3-Kinases: Role in Signal Transduction", "abstract": null, "venue": + "", "year": 2000, "referenceCount": 0, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "2000-04-14", "journal": {"volume": "", "pages": "247-266", "name": ""}, "authors": + [{"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "250a856f7beb9278aa7d0fc5dc6dcd4559de3a39", "externalIds": + {"MAG": "2045201777", "DOI": "10.1074/jbc.M005497200", "CorpusId": 2280830, + "PubMed": "10945990"}, "corpusId": 2280830, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/250a856f7beb9278aa7d0fc5dc6dcd4559de3a39", + "title": "Peptide and Protein Library Screening Defines Optimal Substrate + Motifs for AKT/PKB*", "abstract": "AKT was originally identified as a proto-oncogene + with a pleckstrin homology and Ser/Thr protein kinase domains. Recent studies + revealed that AKT regulates a variety of cellular functions including cell + survival, cell growth, cell differentiation, cell cycle progression, transcription, + translation, and cellular metabolism. To clarify the substrate specificity + of AKT, we have used an oriented peptide library approach to determine optimal + amino acids at positions N-terminal and C-terminal to the site of phosphorylation. + The predicted optimal peptide substrate (Arg-Lys-Arg-Xaa-Arg-Thr-Tyr-Ser*-Phe-Gly + where Ser* is the phosphorylation site) has similarities to but is distinct + from optimal substrates that we previously defined for related basophilic + protein kinases such as protein kinase A, Ser/Arg-rich kinases, and protein + kinase C family members. The positions most important for highV max/K m ratio + were Arg-3>Arg-5>Arg-7. The substrate specificity of AKT was further investigated + by screening a \u03bbGEX phage HeLa cell cDNA expression library. All of the + substrates identified by this procedure contained Arg-Xaa-Arg-Xaa-Xaa-(Ser/Thr) + motifs and were in close agreement with the motif identified by peptide library + screening. The results of this study should help in prediction of likely AKT + substrates from primary sequences.", "venue": "Journal of Biological Chemistry", + "year": 2000, "referenceCount": 93, "citationCount": 401, "influentialCitationCount": + 19, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925820887171/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2000-11-17", "journal": {"volume": + "275", "pages": "36108 - 36115", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "3091430", "name": "T. Obata"}, {"authorId": "88402408", + "name": "M. Yaffe"}, {"authorId": "39756254", "name": "G. Leparc"}, {"authorId": + "2071966448", "name": "Elizabeth T. Piro"}, {"authorId": "3319953", "name": + "H. Maegawa"}, {"authorId": "2064884851", "name": "Atsunori Kashiwagi"}, {"authorId": + "6808657", "name": "R. Kikkawa"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "305b7cbff881b531508563375b6dcb98758504ac", "externalIds": {"MAG": + "2063074486", "DOI": "10.1074/JBC.275.8.6022", "CorpusId": 85250354}, "corpusId": + 85250354, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/305b7cbff881b531508563375b6dcb98758504ac", + "title": "Impaired Kit- but Not Fc\u03b5RI-initiated Mast Cell Activation + in the Absence of Phosphoinositide 3-Kinase p85\u03b1 Gene Products*", "abstract": + "The class IAphosphoinositide 3-kinases (PI3Ks) consist of a 110-kDa catalytic + domain and a regulatory subunit encoded by the p85\u03b1, p85\u03b2, or p55\u03b3 + genes. We have determined the effects of disrupting the p85\u03b1 gene on + the responses of mast cells stimulated by the cross-linking of Kit and Fc\u03b5RI, + receptors that reflect innate and adaptive responses, respectively. The absence + of p85\u03b1 gene products partially inhibited Kit ligand/stem cell factor-induced + secretory granule exocytosis, proliferation, and phosphorylation of the serine/threonine + kinase Akt. In contrast, p85\u03b1 gene products were not required for Fc\u03b5RI-initiated + exocytosis and phosphorylation of Akt. LY294002, which inhibits all classes + of PI3Ks, strongly suppressed Kit- and Fc\u03b5RI-induced responses in p85\u03b1 + \u2212/\u2212 mast cells, revealing the contribution of another PI3K family + member(s). In contrast to B lymphocytes, mast cell proliferation was not dependent + on Bruton''s tyrosine kinase, a downstream effector of PI3K, revealing a distinct + pathway of PI3K-dependent proliferation in mast cells. Our findings represent + the first example of receptor-specific usage of different PI3K family members + in a single cell type. In addition, because Kit- but not Fc\u03b5RI-initiated + signaling is associated with mast cell proliferation, the results provide + evidence that distinct biologic functions signaled by these two receptors + may reflect differential usage of PI3Ks.", "venue": "Journal of Biological + Chemistry", "year": 2000, "referenceCount": 77, "citationCount": 84, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925818306434/pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "2000-02-25", "journal": {"volume": + "275", "pages": "6022 - 6029", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "1403245024", "name": "J. Lu-Kuo"}, {"authorId": + "6241317", "name": "D. Fruman"}, {"authorId": "88707799", "name": "D. M. Joyal"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3648966", "name": + "H. Katz"}]}, {"paperId": "351bb8a44f2b5a46670f652d0326e39a703f7c9c", "externalIds": + {"MAG": "2159310898", "DOI": "10.1093/emboj/19.24.6778", "CorpusId": 10566416, + "PubMed": "11118213"}, "corpusId": 10566416, "publicationVenue": {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", + "name": "EMBO Journal", "type": "journal", "alternate_names": ["The EMBO Journal", + "EMBO J"], "issn": "0261-4189", "url": "http://embojournal.npgjournals.com/", + "alternate_urls": ["http://emboj.embopress.org/"]}, "url": "https://www.semanticscholar.org/paper/351bb8a44f2b5a46670f652d0326e39a703f7c9c", + "title": "TAZ: a novel transcriptional co\u2010activator regulated by interactions + with 14\u20103\u20103 and PDZ domain proteins", "abstract": "The highly conserved + and ubiquitously expressed 14\u20103\u20103 proteins regulate differentiation, + cell cycle progression and apoptosis by binding intracellular phosphoproteins + involved in signal transduction. By screening in vitro translated cDNA pools + for the ability to bind 14\u20103\u20103, we identified a novel transcriptional + co\u2010activator, TAZ (transcriptional co\u2010activator with PDZ\u2010binding + motif) as a 14\u20103\u20103\u2010binding molecule. TAZ shares homology with + Yes\u2010associated protein (YAP), contains a WW domain and functions as a + transcriptional co\u2010activator by binding to the PPXY motif present on + transcription factors. 14\u20103\u20103 binding requires TAZ phosphorylation + on a single serine residue, resulting in the inhibition of TAZ transcriptional + co\u2010activation through 14\u20103\u20103\u2010mediated nuclear export. + The C\u2010terminus of TAZ contains a highly conserved PDZ\u2010binding motif + that localizes TAZ into discrete nuclear foci and is essential for TAZ\u2010stimulated + gene transcription. TAZ uses this same motif to bind the PDZ domain\u2010containing + protein NHERF\u20102, a molecule that tethers plasma membrane ion channels + and receptors to cytoskeletal actin. TAZ may link events at the plasma membrane + and cytoskeleton to nuclear transcription in a manner that can be regulated + by 14\u20103\u20103.", "venue": "EMBO Journal", "year": 2000, "referenceCount": + 71, "citationCount": 669, "influentialCitationCount": 52, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc305881?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2000-12-15", "journal": {"volume": + "19", "name": "The EMBO Journal"}, "authors": [{"authorId": "2170836648", + "name": "Fumihiko Kanai"}, {"authorId": "40278978", "name": "P. Marignani"}, + {"authorId": "3871851", "name": "D. Sarbassova"}, {"authorId": "46728276", + "name": "R. Yagi"}, {"authorId": "143838334", "name": "R. Hall"}, {"authorId": + "5469802", "name": "M. Donowitz"}, {"authorId": "13888755", "name": "Akihiko + Hisaminato"}, {"authorId": "152910706", "name": "Tsutomu Fujiwara"}, {"authorId": + "2132382", "name": "Yoshiaki Ito"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "88402408", "name": "M. Yaffe"}]}, {"paperId": "3f02cf242b8e7e66bdfc6513cdb9f800fbe19584", + "externalIds": {"MAG": "2031365072", "DOI": "10.1074/jbc.M001002200", "CorpusId": + 42596932, "PubMed": "10801797"}, "corpusId": 42596932, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/3f02cf242b8e7e66bdfc6513cdb9f800fbe19584", + "title": "Utilization of Oriented Peptide Libraries to Identify Substrate + Motifs Selected by ATM*", "abstract": "The ataxia telangiectasiamutated (ATM) + gene encodes a serine/threonine protein kinase that plays a critical role + in genomic surveillance and development. Here, we use a peptide library approach + to define thein vitro substrate specificity of ATM kinase activity. The peptide + library analysis identified an optimal sequence with a central core motif + of LSQE that is preferentially phosphorylated by ATM. The contributions of + the amino acids surrounding serine in the LSQE motif were assessed by utilizing + specific peptide libraries or individual peptide substrates. All amino acids + comprising the LSQE sequence were critical for maximum peptide substrate suitability + for ATM. The DNA-dependent proteinkinase (DNA-PK), a Ser/Thr kinase related + to ATM and important in DNA repair, was compared with ATM in terms of peptide + substrate selectivity. DNA-PK was found to be unique in its preference of + neighboring amino acids to the phosphorylated serine. Peptide library analyses + defined a preferred amino acid motif for ATM that permits clear distinctions + between ATM and DNA-PK kinase activity. Data base searches using the library-derived + ATM sequence identified previously characterized substrates of ATM, as well + as novel candidate substrate targets that may function downstream in ATM-directed + signaling pathways.", "venue": "Journal of Biological Chemistry", "year": + 2000, "referenceCount": 63, "citationCount": 185, "influentialCitationCount": + 11, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/275/30/22719.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2000-07-28", "journal": {"volume": + "275", "pages": "22719 - 22727", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "2072861267", "name": "T. O''Neill"}, {"authorId": + "2187573102", "name": "Alison J. Dwyer"}, {"authorId": "48277931", "name": + "Y. Ziv"}, {"authorId": "153637109", "name": "D. Chan"}, {"authorId": "1398713833", + "name": "S. Lees-Miller"}, {"authorId": "2187574258", "name": "Robert H. Abraham"}, + {"authorId": "5000276", "name": "J. Lai"}, {"authorId": "50570936", "name": + "D. Hill"}, {"authorId": "35164321", "name": "Y. Shiloh"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "2508043", "name": "G. Rathbun"}]}, {"paperId": + "45f118bf141e32361ec9bd40541df12e3dd7bd5a", "externalIds": {"MAG": "2897380573", + "CorpusId": 186967450}, "corpusId": 186967450, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/45f118bf141e32361ec9bd40541df12e3dd7bd5a", + "title": "Methodes et reactifs permettant de reguler l''expression genique", + "abstract": "L''invention concerne une approche generale permettant d''identifier + des sequences d''activation transcriptionnelle minimales specifiques d''un + domaine. On a notamment decouvert que les approches utilisant la diversite + moleculaire peuvent servir a decouvrir des activateurs synthetiques specifiques + d''un domaine de co-activateur et que l''activation transcriptionnelle peut + etre modulee a volonte au niveau du recrutement du co-activateur.", "venue": + "", "year": 2000, "referenceCount": 4, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [], "publicationTypes": null, "publicationDate": "2000-08-31", "journal": + {"volume": "", "name": ""}, "authors": [{"authorId": "1788876", "name": "J. + Frangioni"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4892627", + "name": "M. Montminy"}]}, {"paperId": "4748293c0b008fea4e631c7674be6b2fe754bb06", + "externalIds": {"MAG": "2118108045", "DOI": "10.1073/PNAS.110146697", "CorpusId": + 23719097, "PubMed": "10829070"}, "corpusId": 23719097, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/4748293c0b008fea4e631c7674be6b2fe754bb06", + "title": "A sensitized genetic system for the analysis of murine B lymphocyte + signal transduction pathways dependent on Bruton''s tyrosine kinase.", "abstract": + "Modifier screens have been powerful genetic tools to define signaling pathways + in lower organisms. The identification of modifier loci in mice has begun + to allow a similar dissection of mammalian signaling pathways. Transgenic + mice (Btk(lo)) expressing 25% of endogenous levels of Bruton''s tyrosine kinase + (Btk) have B cell functional responses between those of wild-type and Btk(-/-) + mice. We asked whether reduced dosage or complete deficiency of genes previously + implicated as Btk regulators would modify the Btk(lo) phenotype. We used two + independent assays of Btk-dependent B cell function. Proliferative response + to B cell antigen receptor cross-linking in vitro was chosen as an example + of a relatively simple, well-defined signaling system. In vivo response to + type II T-independent antigens (TI-II) measures complex interactions among + multiple cell types over time and may identify additional Btk pathways. All + modifiers identified differentially affected these two assays, indicating + that Btk mediates these processes via distinct mechanisms. Loss of Lyn, PTEN + (phosphatase and tensin homolog), or SH2-containing inositol phosphatase suppressed + the Btk(lo) phenotype in vitro but not in vivo, whereas CD19 and the p85alpha + form of phosphoinositide 3-kinase behaved as Btk(lo) enhancers in vivo but + not in vitro. Effects of Lyn, PTEN, or p85alpha haploinsufficiency were observed. + Haploinsufficiency or complete deficiency of protein kinase C beta, Fyn, CD22, + Galphaq, or Galpha11 had no detectable effect on the function of Btk(lo) B + cells. A transgenic system creating a reduction in dosage of Btk can therefore + be used to identify modifier loci that affect B cell responses and quantitatively + rank their contribution to Btk-mediated processes.", "venue": "Proceedings + of the National Academy of Sciences of the United States of America", "year": + 2000, "referenceCount": 75, "citationCount": 42, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/97/12/6687.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2000-06-06", "journal": {"volume": + "97 12", "pages": "\n 6687-92\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "4830084", "name": "A. Satterthwaite"}, {"authorId": "2074386301", + "name": "F. Willis"}, {"authorId": "10734552", "name": "P. Kanchanastit"}, + {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "1436339877", "name": "C. Helgason"}, {"authorId": + "5005325", "name": "R. Humphries"}, {"authorId": "3604835", "name": "C. Lowell"}, + {"authorId": "2114372197", "name": "M. Simon"}, {"authorId": "5361867", "name": + "M. Leitges"}, {"authorId": "6314235", "name": "A. Tarakhovsky"}, {"authorId": + "3618932", "name": "T. Tedder"}, {"authorId": "3638435", "name": "R. Lesche"}, + {"authorId": "2107347010", "name": "H. Wu"}, {"authorId": "6614731", "name": + "O. Witte"}]}, {"paperId": "510bba74fd28a7939e9d164841a8fae836ad9928", "externalIds": + {"MAG": "1607067835", "DOI": "10.1038/80280", "CorpusId": 6829642, "PubMed": + "11017047"}, "corpusId": 6829642, "publicationVenue": {"id": "458166b3-de17-4bf3-bbbb-e53782de2f0f", + "name": "Nature Biotechnology", "type": "journal", "alternate_names": ["Nat + Biotechnol"], "issn": "1087-0156", "url": "http://www.nature.com/nbt/", "alternate_urls": + ["http://www.nature.com/nbt"]}, "url": "https://www.semanticscholar.org/paper/510bba74fd28a7939e9d164841a8fae836ad9928", + "title": "Minimal activators that bind to the KIX domain of p300/CBP identified + by phage display screening", "abstract": null, "venue": "Nature Biotechnology", + "year": 2000, "referenceCount": 33, "citationCount": 45, "influentialCitationCount": + 3, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "2000-10-01", "journal": {"volume": "18", "pages": "1080-1085", "name": "Nature + Biotechnology"}, "authors": [{"authorId": "1788876", "name": "J. Frangioni"}, + {"authorId": "2104786467", "name": "Leah M. LaRiccia"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4892627", "name": "M. Montminy"}]}, {"paperId": + "69c798e12670d7759eb6c90a156887c9b4414ae2", "externalIds": {"MAG": "1980152312", + "DOI": "10.1016/S0091-6749(00)90955-2", "CorpusId": 71437176}, "corpusId": + 71437176, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/69c798e12670d7759eb6c90a156887c9b4414ae2", + "title": "527 Impaird Kit- but not Fc\u03b5RI-mediated mast cell activation + in the absence of regulatory subunits encoded by the phosphoinositide 3-kinase + (PI3K) p85\u03b1 gene", "abstract": null, "venue": "", "year": 2000, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": null, "authors": + [{"authorId": "1403245024", "name": "J. Lu-Kuo"}, {"authorId": "6241317", + "name": "D. Fruman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3648966", "name": "H. Katz"}]}, {"paperId": "6e29e558df951b9811c08f727893460abfe4762e", + "externalIds": {"MAG": "2031874417", "DOI": "10.1016/S0960-9822(00)00315-8", + "CorpusId": 20209389, "PubMed": "10679324"}, "corpusId": 20209389, "publicationVenue": + {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", "name": "Current Biology", + "type": "journal", "alternate_names": ["Curr Biology"], "issn": "0960-9822", + "url": "http://www.current-biology.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/09609822"]}, + "url": "https://www.semanticscholar.org/paper/6e29e558df951b9811c08f727893460abfe4762e", + "title": "Type I\u03b1 phosphatidylinositol-4-phosphate 5-kinase mediates + Rac-dependent actin assembly", "abstract": null, "venue": "Current Biology", + "year": 2000, "referenceCount": 19, "citationCount": 242, "influentialCitationCount": + 10, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0960982200003158/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "2000-02-01", "journal": {"volume": + "10", "pages": "153-156", "name": "Current Biology"}, "authors": [{"authorId": + "4661935", "name": "K. Tolias"}, {"authorId": "2999768", "name": "J. Hartwig"}, + {"authorId": "2805489", "name": "H. Ishihara"}, {"authorId": "49569235", "name": + "Y. Shibasaki"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2972505", "name": "C. Carpenter"}]}, {"paperId": "718952afde5c86e117085296a6dfc5ebc18c3e03", + "externalIds": {"MAG": "2067837318", "DOI": "10.1093/emboj/19.11.2537", "CorpusId": + 23456358, "PubMed": "10835352"}, "corpusId": 23456358, "publicationVenue": + {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": + "journal", "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", + "url": "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/718952afde5c86e117085296a6dfc5ebc18c3e03", + "title": "The conserved phosphoinositide 3\u2010kinase pathway determines + heart size in mice", "abstract": "Phosphoinositide 3\u2010kinase (PI3K) has + been shown to regulate cell and organ size in Drosophila, but the role of + PI3K in vertebrates in vivo is not well understood. To examine the role of + PI3K in intact mammalian tissue, we have created and characterized transgenic + mice expressing constitutively active or dominant\u2010negative mutants of + PI3K in the heart. Cardiac\u2010 specific expression of constitutively active + PI3K resulted in mice with larger hearts, while dominant\u2010negative PI3K + resulted in mice with smaller hearts. The increase or decrease in heart size + was associated with comparable increase or decrease in myocyte size. Cardiomyopathic + changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile + dysfunction, were not observed in either of the transgenic mice. Thus, the + PI3K pathway is necessary and sufficient to promote organ growth in mammals.", + "venue": "EMBO Journal", "year": 2000, "referenceCount": 78, "citationCount": + 623, "influentialCitationCount": 39, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc212739?pdf=render", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2000-06-01", "journal": {"volume": "19", "name": "The + EMBO Journal"}, "authors": [{"authorId": "6946601", "name": "T. Shioi"}, {"authorId": + "2302010", "name": "P. Kang"}, {"authorId": "1995988", "name": "P. Douglas"}, + {"authorId": "15410490", "name": "J. Hampe"}, {"authorId": "7777071", "name": + "C. Yballe"}, {"authorId": "6704546", "name": "J. Lawitts"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "47072554", "name": "S. Izumo"}]}, + {"paperId": "cedfb2fc68646aed19c4250779520e3f5804b576", "externalIds": {"MAG": + "1591760396", "DOI": "10.1016/S0076-6879(00)28397-3", "CorpusId": 41373492, + "PubMed": "11075345"}, "corpusId": 41373492, "publicationVenue": {"id": "1e7039c8-e30c-4af0-b7d3-f5e05dff5d21", + "name": "Methods in Enzymology", "type": "journal", "alternate_names": ["Method + Enzymol"], "issn": "0076-6879", "alternate_issns": ["1557-7988"], "url": "https://www.elsevier.com/books/book-series/methods-in-enzymology", + "alternate_urls": ["http://www.sciencedirect.com/science/bookseries/00766879"]}, + "url": "https://www.semanticscholar.org/paper/cedfb2fc68646aed19c4250779520e3f5804b576", + "title": "Mapping specificity determinants for protein-protein association + using protein fusions and random peptide libraries.", "abstract": null, "venue": + "Methods in Enzymology", "year": 2000, "referenceCount": 11, "citationCount": + 33, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "328", "pages": "\n 157-70\n ", + "name": "Methods in enzymology"}, "authors": [{"authorId": "88402408", "name": + "M. Yaffe"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "ed2d152a9cfb677f52f8623ce8093be7969974b7", "externalIds": {"MAG": "2082678397", + "DOI": "10.1016/S1097-2765(05)00085-7", "CorpusId": 33957326, "PubMed": "11090635"}, + "corpusId": 33957326, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/ed2d152a9cfb677f52f8623ce8093be7969974b7", + "title": "A peptide library approach identifies a specific inhibitor for the + ZAP-70 protein tyrosine kinase.", "abstract": null, "venue": "Molecules and + Cells", "year": 2000, "referenceCount": 13, "citationCount": 34, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276505000857/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "2000-10-01", "journal": {"volume": "6 4", "pages": "\n 969-74\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "153448781", "name": "K. + Nishikawa"}, {"authorId": "5824638", "name": "S. Sawasdikosol"}, {"authorId": + "6241317", "name": "D. Fruman"}, {"authorId": "5000276", "name": "J. Lai"}, + {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "2549319", "name": + "S. Burakoff"}, {"authorId": "88402408", "name": "M. Yaffe"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "f21574d4da5878510edd4fad62982f8e452d0bc8", + "externalIds": {"MAG": "2043363499", "DOI": "10.1074/jbc.275.3.2219", "CorpusId": + 46124821, "PubMed": "10636929"}, "corpusId": 46124821, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/f21574d4da5878510edd4fad62982f8e452d0bc8", + "title": "Biochemical Interactions Integrating Itk with the T Cell Receptor-initiated + Signaling Cascade*", "abstract": "Itk, a Tec family tyrosine kinase, acts + downstream of Lck and phosphatidylinositol 3\u2032-kinase to facilitate T + cell receptor (TCR)-dependent calcium influxes and increases in extracellular-regulated + kinase activity. Here we demonstrate interactions between Itk and crucial + components of TCR-dependent signaling pathways. First, the inositide-binding + pocket of the Itk pleckstrin homology domain directs the constitutive association + of Itk with buoyant membranes that are the primary site of TCR activation + and are enriched in both Lck and LAT. This association is required for the + transphosphorylation of Itk. Second, the Itk proline-rich region binds to + Grb2 and LAT. Third, the Itk Src homology (SH3) 3 and SH2 domains interact + cooperatively with Syk-phosphorylated SLP-76. Notably, SLP-76 contains a predicted + binding motif for the Itk SH2 domain and binds to full-length Itk in vitro. + Finally, we show that kinase-inactive Itk can antagonize the SLP-76-dependent + activation of NF-AT. The inhibition of NF-AT activation depends on the Itk + pleckstrin homology domain, proline-rich region, and SH2 domain. Together, + these observations suggest that multivalent interactions recruit Itk to LAT-nucleated + signaling complexes and facilitate the activation of LAT-associated phospholipase + C\u03b31 by Itk.", "venue": "Journal of Biological Chemistry", "year": 2000, + "referenceCount": 85, "citationCount": 303, "influentialCitationCount": 27, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/275/3/2219.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "2000-01-21", "journal": + {"volume": "275", "pages": "2219 - 2230", "name": "The Journal of Biological + Chemistry"}, "authors": [{"authorId": "4808985", "name": "S. Bunnell"}, {"authorId": + "1907024", "name": "M. Diehn"}, {"authorId": "88402408", "name": "M. Yaffe"}, + {"authorId": "6175740", "name": "P. Findell"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "1905806", "name": "L. Berg"}]}, {"paperId": "10d1177f4a523a485ea2389f4b737795f54631f0", + "externalIds": {"MAG": "2028211858", "DOI": "10.1126/SCIENCE.285.5436.2129", + "CorpusId": 39529372, "PubMed": "10497131"}, "corpusId": 39529372, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/10d1177f4a523a485ea2389f4b737795f54631f0", + "title": "Affinity-driven peptide selection of an NFAT inhibitor more selective + than cyclosporin A.", "abstract": "The flow of information from calcium-mobilizing + receptors to nuclear factor of activated T cells (NFAT)-dependent genes is + critically dependent on interaction between the phosphatase calcineurin and + the transcription factor NFAT. A high-affinity calcineurin-binding peptide + was selected from combinatorial peptide libraries based on the calcineurin + docking motif of NFAT. This peptide potently inhibited NFAT activation and + NFAT-dependent expression of endogenous cytokine genes in T cells, without + affecting the expression of other cytokines that require calcineurin but not + NFAT. Substitution of the optimized peptide sequence into the natural calcineurin + docking site increased the calcineurin responsiveness of NFAT. Compounds that + interfere selectively with the calcineurin-NFAT interaction without affecting + calcineurin phosphatase activity may be useful as therapeutic agents that + are less toxic than current drugs.", "venue": "Science", "year": 1999, "referenceCount": + 29, "citationCount": 587, "influentialCitationCount": 46, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "LettersAndComments"], "publicationDate": "1999-09-24", "journal": {"volume": + "285 5436", "pages": "\n 2129-33\n ", "name": "Science"}, + "authors": [{"authorId": "145087088", "name": "J. Aramburu"}, {"authorId": + "88402408", "name": "M. Yaffe"}, {"authorId": "1401469293", "name": "C. L\u00f3pez-Rodr\u00edguez"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1965988", "name": + "P. Hogan"}, {"authorId": "144619116", "name": "A. Rao"}]}, {"paperId": "15c54f58c4cf7556ecec89fe0f9631f64b8e8300", + "externalIds": {"MAG": "1997712588", "DOI": "10.1016/S1097-2765(00)80206-3", + "CorpusId": 27032155, "PubMed": "10549287"}, "corpusId": 27032155, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/15c54f58c4cf7556ecec89fe0f9631f64b8e8300", + "title": "Crystal structures of the XLP protein SAP reveal a class of SH2 + domains with extended, phosphotyrosine-independent sequence recognition.", + "abstract": null, "venue": "Molecules and Cells", "year": 1999, "referenceCount": + 31, "citationCount": 260, "influentialCitationCount": 12, "isOpenAccess": + true, "openAccessPdf": {"url": "http://www.cell.com/article/S1097276500802063/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1999-10-01", "journal": {"volume": + "4 4", "pages": "\n 555-61\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "4096365", "name": "F. Poy"}, {"authorId": "88402408", + "name": "M. Yaffe"}, {"authorId": "4306050", "name": "J. Sayo\u0301s"}, {"authorId": + "50526125", "name": "K. Saxena"}, {"authorId": "4187907", "name": "M. Morra"}, + {"authorId": "5921216", "name": "J. Sumegi"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4658870", "name": "C. Terhorst"}, {"authorId": + "2026802", "name": "M. Eck"}]}, {"paperId": "1e6e9e1e94938c4235db01a2b7f82554d905da6c", + "externalIds": {"MAG": "2309312299", "DOI": "10.1042/BST0270624", "CorpusId": + 5921491, "PubMed": "10917654"}, "corpusId": 5921491, "publicationVenue": {"id": + "9c7806c9-5d45-4670-86ed-e7e052ef142a", "name": "Biochemical Society Transactions", + "type": "journal", "alternate_names": ["Biochem Soc Trans"], "issn": "0300-5127"}, + "url": "https://www.semanticscholar.org/paper/1e6e9e1e94938c4235db01a2b7f82554d905da6c", + "title": "Phosphoinositide 3-kinase knockout mice: role of p85alpha in B cell + development and proliferation.", "abstract": "Cur. Opin. Cell Biol. 10, 504-5 + I 2 49 Barylko, B., Binns, D., Lin, K. M., Atkinson, M. A,, Jameson, D. M., + Yin, H. L. and Albanesi, J. P. ( I 998) J. Biol. Chern. 273, 379 1-3797 50 + Achiriloaie, M., Barylko, B. and Albanesi, J. P. ( I 999) Mol. Cell. Biol. + 19, 141Ck1415 51 Vallis, Y., Wigge, P., Marks, B., Evans, P. R and McMahon, + H T. ( 1999) Curr. Biol. 9, 257-260 52 Lee, A., Frank, D. W., Marks, M. S. + and Lemrnon, M. A. ( I 999) Cur. Biol. 9, 26 1-264 53 Owen, D. J., Wigge, + P., Vallis, Y., Moore, J. D. A,, Evans, P. R and McMahon, H. T. ( 1998) EMBO + J. 18, 5273-5288", "venue": "Biochemical Society Transactions", "year": 1999, + "referenceCount": 0, "citationCount": 39, "influentialCitationCount": 2, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "1999-08-01", + "journal": {"volume": "27 4", "pages": "\n 624-9\n ", "name": + "Biochemical Society transactions"}, "authors": [{"authorId": "6241317", "name": + "D. Fruman"}, {"authorId": "4818618", "name": "S. Snapper"}, {"authorId": + "7777071", "name": "C. Yballe"}, {"authorId": "31713146", "name": "F. Alt"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "300e7558e448a3a8c809ce7817996c52a890ea6f", + "externalIds": {"MAG": "147860631", "DOI": "10.1007/978-3-642-60162-0_33", + "CorpusId": 41588876, "PubMed": "10396065"}, "corpusId": 41588876, "publicationVenue": + {"id": "35b70977-7c87-4140-8eb7-b63988a12c83", "name": "Current Topics in + Microbiology and Immunology", "type": "journal", "alternate_names": ["Curr + Top Microbiol Immunol"], "issn": "0070-217X", "alternate_issns": ["2196-9965"], + "url": "https://link.springer.com/bookseries/82"}, "url": "https://www.semanticscholar.org/paper/300e7558e448a3a8c809ce7817996c52a890ea6f", + "title": "ATM and lymphoid malignancies; use of oriented peptide libraries + to identify novel substrates of ATM critical in downstream signaling pathways.", + "abstract": null, "venue": "Current Topics in Microbiology and Immunology", + "year": 1999, "referenceCount": 23, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Medicine", "source": + "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": null, "journal": {"volume": + "246", "pages": "\n 267-73; discussion 274\n ", "name": "Current + topics in microbiology and immunology"}, "authors": [{"authorId": "2508043", + "name": "G. Rathbun"}, {"authorId": "48277931", "name": "Y. Ziv"}, {"authorId": + "5000276", "name": "J. Lai"}, {"authorId": "50570936", "name": "D. Hill"}, + {"authorId": "2097710310", "name": "R. Abraham"}, {"authorId": "144157302", + "name": "Y. Shiloh"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "3e835ad09141d38dd5a69263dc72f38b805b404b", "externalIds": {"MAG": "1984418041", + "DOI": "10.1073/PNAS.96.8.4240", "CorpusId": 43439834, "PubMed": "10200246"}, + "corpusId": 43439834, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/3e835ad09141d38dd5a69263dc72f38b805b404b", + "title": "New insights into tumor suppression: PTEN suppresses tumor formation + by restraining the phosphoinositide 3-kinase/AKT pathway.", "abstract": "The + most recently discovered PTEN tumor suppressor gene has been found to be defective + in a large number of human cancers. In addition, germ-line mutations in PTEN + result in the dominantly inherited disease Cowden syndrome, which is characterized + by multiple hamartomas and a high proclivity for developing cancer. A series + of publications over the past year now suggest a mechanism by which PTEN loss + of function results in tumors. PTEN appears to negatively control the phosphoinositide + 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating + the 3 position of phosphoinositides.", "venue": "Proceedings of the National + Academy of Sciences of the United States of America", "year": 1999, "referenceCount": + 76, "citationCount": 2038, "influentialCitationCount": 92, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc33561?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "1999-04-13", "journal": + {"volume": "96 8", "pages": "\n 4240-5\n ", "name": "Proceedings + of the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2291271", "name": + "B. Neel"}]}, {"paperId": "59d9e6ca583c6b393659bd6f00f0c86cbba76fc5", "externalIds": + {"MAG": "1617092022", "DOI": "10.1038/46925", "CorpusId": 5374019, "PubMed": + "10573413"}, "corpusId": 5374019, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/59d9e6ca583c6b393659bd6f00f0c86cbba76fc5", + "title": "Signal transduction: Grabbing phosphoproteins", "abstract": null, + "venue": "Nature", "year": 1999, "referenceCount": 11, "citationCount": 75, + "influentialCitationCount": 2, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["News"], "publicationDate": "1999-11-04", "journal": + {"volume": "402", "pages": "30-31", "name": "Nature"}, "authors": [{"authorId": + "88402408", "name": "M. Yaffe"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "5afc6eee8fb45b431bdea6b2db5dcd480215932e", "externalIds": {"MAG": + "2916153727", "DOI": "10.2210/pdb1qjb/pdb", "CorpusId": 104387460}, "corpusId": + 104387460, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/5afc6eee8fb45b431bdea6b2db5dcd480215932e", + "title": "14-3-3 ZETA/PHOSPHOPEPTIDE COMPLEX (MODE 1)", "abstract": null, + "venue": "", "year": 1999, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "1999-09-15", "journal": null, "authors": [{"authorId": "6239566", "name": + "K. Rittinger"}, {"authorId": "4299977", "name": "J. Budman"}, {"authorId": + "2110980007", "name": "Jian Xu"}, {"authorId": "1906416", "name": "S. Volinia"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4189482", "name": + "S. Smerdon"}, {"authorId": "1958388", "name": "S. Gamblin"}, {"authorId": + "88402408", "name": "M. Yaffe"}]}, {"paperId": "743aaaadb1cded9b403f4eee827844492b4d7ee0", + "externalIds": {"MAG": "2002127663", "DOI": "10.1074/jbc.274.13.8347", "CorpusId": + 6022170, "PubMed": "10085060"}, "corpusId": 6022170, "publicationVenue": {"id": + "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological Chemistry", + "type": "journal", "alternate_names": ["J Biological Chem"], "issn": "0021-9258", + "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", "alternate_urls": + ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": "https://www.semanticscholar.org/paper/743aaaadb1cded9b403f4eee827844492b4d7ee0", + "title": "The Role of Phosphoinositide 3-Kinase Lipid Products in Cell Function*", + "abstract": "Phosphoinositide 3-kinases (PI 3-Ks) are a subfamily of lipid + kinases that catalyze the addition of a phosphate molecule specifically to + the 3-position of the inositol ring of phosphoinositides. Phosphatidylinositol + (PtdIns), the precursor of all phosphoinositides (PI), constitutes less than + 10% of the total lipid in eukaryotic cell membranes (Fig. 1). Approximately + 5% of cellular PI is phosphorylated at the 4-position (PtdIns-4-P), and another + 5% is phosphorylated at both the 4and 5-positions (PtdIns-4,5-P2). However, + less than 0.25% of the total inositol-containing lipids are phosphorylated + at the 3-position, consistent with the idea that these lipids exert specific + regulatory functions inside the cell, as opposed to a structural function. + To date, nine members of the PI 3-K family have been isolated from mammalian + cells. They are grouped, as suggested by Domin and Waterfield (1), into three + classes according to the molecules that they preferentially utilize as substrates. + Four different lipid products can be generated by the different PI 3-K members: + the singly phosphorylated form PtdIns-3-P; the doubly phosphorylated forms + PtdIns-3,4-P2 and PtdIns-3,5-P2; and finally the triply phosphorylated form + PtdIns-3,4,5-P3 (Fig. 1). PI 3-K was first described as a PI kinase activity + associated with the viral oncoproteins, v-Src, v-Ros, and polyomavirus middle + T. Mutational studies of these oncoproteins more than 10 years ago indicated + a critical role for the associated PI kinase in cell transformation (reviewed + by Ref. 2). Recent advances in the field have been achieved by the development + of new techniques to probe for the direct targets of PI 3-K lipid products. + The chemical synthesis of short chain fatty acid versions of these lipids + (3\u20135) has been a crucial step in determining the specificity of lipid-binding + proteins. Additionally, new cloning strategies have been developed to isolate + new lipid-binding proteins (6). Here we will review the most recent advances + in our understanding of the role of PI 3-K in cell function by dissecting + the contribution of each of its lipid products.", "venue": "Journal of Biological + Chemistry", "year": 1999, "referenceCount": 91, "citationCount": 1053, "influentialCitationCount": + 49, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/274/13/8347.full.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "1999-03-26", "journal": + {"volume": "274", "pages": "8347 - 8350", "name": "The Journal of Biological + Chemistry"}, "authors": [{"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "8de62be269797f581b996518e6792f88390d20f8", + "externalIds": {"MAG": "2068921184", "DOI": "10.1006/BBRC.1999.1150", "CorpusId": + 5619185, "PubMed": "10462494"}, "corpusId": 5619185, "publicationVenue": {"id": + "1a9c698b-7fe4-4444-b391-208b4b2326e2", "name": "Biochemical and Biophysical + Research Communications - BBRC", "type": "journal", "alternate_names": ["Biochem + Biophys Res Commun", "Biochemical and Biophysical Research Communications", + "Biochem Biophys Res Commun BBRC"], "issn": "0006-291X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description", + "alternate_urls": ["http://www.idealibrary.com/links/toc/bbrc", "https://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/", + "http://www.sciencedirect.com/science/journal/0006291X"]}, "url": "https://www.semanticscholar.org/paper/8de62be269797f581b996518e6792f88390d20f8", + "title": "Mouse phosphoinositide 3-kinase p110alpha gene: cloning, structural + organization, and localization to chromosome 3 band B.", "abstract": "Phosphoinositide + 3-Kinases (PI3-Kinases) are a family of dual specificity enzymes with a unique + lipid kinase activity toward the D-3 position of the inositol ring of phosphoinositides + and a less well characterized serine/threonine protein kinase activity. Class + IA PI3-Kinases comprise a 110-120 kDa catalytic subunit (usually termed p110) + and an 85 kDa or 50 to 55 kDa regulatory subunit (often called p85). cDNAs + for three mammalian Class IA PI3-Kinase catalytic subunits designated p110alpha, + p110beta, and p110delta have been cloned from several species. A YAC clone + for the human p110alpha gene has also been cloned and mapped to chromosome + 3q26.3. However, structural organization for any of the PI3-Kinase p110alpha + genes has not been reported. Here, we report the cloning, structural organization, + and chromosomal localization of the mouse PI3-Kinase p110alpha gene. The translated + portion of the mouse p110alpha gene is encoded by 19 exons that span at least + 24 kb. Dual color fluorescence in situ hybridization (FISH) was performed + to determine the chromosomal localization of the mouse PI3-Kinase p110alpha + gene. FISH results and DAPI banding demonstrated localization of the p110alpha + gene to band B on mouse chromosome 3, a region syntenic with human chromosome + 3q26.3.", "venue": "Biochemical and Biophysical Research Communications - + BBRC", "year": 1999, "referenceCount": 27, "citationCount": 6, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1999-08-27", "journal": {"volume": "262 2", "pages": "\n 438-42\n ", + "name": "Biochemical and biophysical research communications"}, "authors": + [{"authorId": "3490135", "name": "I. Aksoy"}, {"authorId": "4025207", "name": + "M. Ramsey"}, {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "48355989", + "name": "S. Aksoy"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "33378554", "name": "J. Tucker"}, {"authorId": "6665338", "name": "T. Roberts"}]}, + {"paperId": "a1110c534e9712312077bff378534bb86f809c9c", "externalIds": {"MAG": + "1975573101", "DOI": "10.1016/S0092-8674(00)80792-8", "CorpusId": 17886164, + "PubMed": "10399908"}, "corpusId": 17886164, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/a1110c534e9712312077bff378534bb86f809c9c", + "title": "Phosphoinositide Binding Domains Embracing 3-Phosphate", "abstract": + null, "venue": "Cell", "year": 1999, "referenceCount": 33, "citationCount": + 136, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867400807928/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "1999-06-25", "journal": {"volume": + "97", "pages": "817-820", "name": "Cell"}, "authors": [{"authorId": "6241317", + "name": "D. Fruman"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "a9e6e4528afd7d105cb34011caca7496200b8fe3", + "externalIds": {"MAG": "2008065206", "DOI": "10.1126/SCIENCE.283.5400.393", + "CorpusId": 7445833, "PubMed": "9888855"}, "corpusId": 7445833, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/a9e6e4528afd7d105cb34011caca7496200b8fe3", + "title": "Impaired B cell development and proliferation in absence of phosphoinositide + 3-kinase p85alpha.", "abstract": "Phosphoinositide 3-kinase (PI3K) activation + has been implicated in many cellular responses, including fibroblast growth, + transformation, survival, and chemotaxis. Although PI3K is activated by several + agents that stimulate T and B cells, the role of PI3K in lymphocyte function + is not clear. The mouse gene encoding the PI3K adapter subunit p85alpha and + its splice variants p55alpha and p50alpha was disrupted. Most p85alpha-p55alpha-p50alpha-/- + mice die within days after birth. Lymphocyte development and function was + studied with the use of the RAG2-deficient blastocyst complementation system. + Chimeric mice had reduced numbers of peripheral mature B cells and decreased + serum immunoglobulin. The B cells that developed had diminished proliferative + responses to antibody to immunoglobulin M, antibody to CD40, and lipopolysaccharide + stimulation and decreased survival after incubation with interleukin-4. In + contrast, T cell development and proliferation was normal. This phenotype + is similar to defects observed in mice lacking the tyrosine kinase Btk.", + "venue": "Science", "year": 1999, "referenceCount": 23, "citationCount": 695, + "influentialCitationCount": 20, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Medicine", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1999-01-15", "journal": {"volume": "283 5400", "pages": "\n 393-7\n ", + "name": "Science"}, "authors": [{"authorId": "6241317", "name": "D. Fruman"}, + {"authorId": "4818618", "name": "S. Snapper"}, {"authorId": "7777071", "name": + "C. Yballe"}, {"authorId": "49326303", "name": "L. Davidson"}, {"authorId": + "2107575746", "name": "J. Y. Yu"}, {"authorId": "31713146", "name": "F. Alt"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ae566410e977074dcd0bd185e95d2b519da3e7d8", + "externalIds": {"MAG": "2005131087", "DOI": "10.1074/jbc.274.11.7489", "CorpusId": + 12756819, "PubMed": "10066815"}, "corpusId": 12756819, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/ae566410e977074dcd0bd185e95d2b519da3e7d8", + "title": "The SH2 Domain-containing Inositol 5\u2032-Phosphatase (SHIP) Recruits + the p85 Subunit of Phosphoinositide 3-Kinase during Fc\u03b3RIIb1-mediated + Inhibition of B Cell Receptor Signaling*", "abstract": "Coligation of Fc\u03b3RIIb1 + with the B cell receptor (BCR) or Fc\u03b5RI on mast cells inhibits B cell + or mast cell activation. Activity of the inositol phosphatase SHIP is required + for this negative signal. In vitro, SHIP catalyzes the conversion of the phosphoinositide + 3-kinase (PI3K) product phosphatidylinositol 3,4,5-trisphosphate (PIP3) into + phosphatidylinositol 3,4-bisphosphate. Recent data demonstrate that coligation + of Fc\u03b3RIIb1 with BCR inhibits PIP3-dependent Btk (Bruton\u2019s tyrosine + kinase) activation and the Btk-dependent generation of inositol trisphosphate + that regulates sustained calcium influx. In this study, we provide evidence + that coligation of Fc\u03b3RIIb1 with BCR induces binding of PI3K to SHIP. + This interaction is mediated by the binding of the SH2 domains of the p85 + subunit of PI3K to a tyrosine-based motif in the C-terminal region of SHIP. + Furthermore, the generation of phosphatidylinositol 3,4-bisphosphate was only + partially reduced during coligation of BCR with Fc\u03b3RIIb1 despite a drastic + reduction in PIP3. In contrast to the complete inhibition of Tec kinase-dependent + calcium signaling, activation of the serine/threonine kinase Akt was partially + preserved during BCR and Fc\u03b3RIIb1 coligation. The association of PI3K + with SHIP may serve to activate PI3K and to regulate downstream events such + as B cell activation-induced apoptosis.", "venue": "Journal of Biological + Chemistry", "year": 1999, "referenceCount": 39, "citationCount": 71, "influentialCitationCount": + 3, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925818370261/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1999-03-12", "journal": {"volume": "274", "pages": "7489 + - 7494", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "1871947", "name": "N. Gupta"}, {"authorId": "4727704", "name": "A. Scharenberg"}, + {"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "145931354", "name": "J. Kinet"}, {"authorId": + "35267053", "name": "Eric O Long"}]}, {"paperId": "c0b7687500595ce89a8f22d2fa8878f05e8ae09a", + "externalIds": {"MAG": "2793367634", "DOI": "10.2210/pdb1qja/pdb", "CorpusId": + 103146693}, "corpusId": 103146693, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/c0b7687500595ce89a8f22d2fa8878f05e8ae09a", + "title": "14-3-3 ZETA/PHOSPHOPEPTIDE COMPLEX (MODE 2)", "abstract": null, + "venue": "", "year": 1999, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "1999-09-15", "journal": null, "authors": [{"authorId": "6239566", "name": + "K. Rittinger"}, {"authorId": "4299977", "name": "J. Budman"}, {"authorId": + "2110980007", "name": "Jian Xu"}, {"authorId": "1906416", "name": "S. Volinia"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4189482", "name": + "S. Smerdon"}, {"authorId": "1958388", "name": "S. Gamblin"}, {"authorId": + "88402408", "name": "M. Yaffe"}]}, {"paperId": "db10b9b7ad6fba1678dd63a72b571eabc152d9ec", + "externalIds": {"MAG": "1964622351", "DOI": "10.1016/S0009-3084(99)00019-5", + "CorpusId": 2918480, "PubMed": "10358929"}, "corpusId": 2918480, "publicationVenue": + {"id": "556509f4-0eb1-4dc2-b738-f76b2812717f", "name": "Chemistry and Physics + of Lipids", "type": "journal", "alternate_names": ["Chem Phys Lipid"], "issn": + "0009-3084", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/506036/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00093084", + "https://www.journals.elsevier.com/chemistry-and-physics-of-lipids"]}, "url": + "https://www.semanticscholar.org/paper/db10b9b7ad6fba1678dd63a72b571eabc152d9ec", + "title": "Pathways for phosphoinositide synthesis.", "abstract": null, "venue": + "Chemistry and Physics of Lipids", "year": 1999, "referenceCount": 59, "citationCount": + 86, "influentialCitationCount": 7, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "1999-04-01", "journal": {"volume": "98 1-2", "pages": + "\n 69-77\n ", "name": "Chemistry and physics of lipids"}, + "authors": [{"authorId": "4661935", "name": "K. Tolias"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "e2e9a4dc4a425eec2a8962b5be9a78cbe8c801d3", + "externalIds": {"MAG": "2976585521", "DOI": "10.2210/pdb14ps/pdb", "CorpusId": + 204112664}, "corpusId": 204112664, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e2e9a4dc4a425eec2a8962b5be9a78cbe8c801d3", + "title": "14-3-3 ZETA/PHOSPHOPEPTIDE COMPLEX", "abstract": null, "venue": + "", "year": 1999, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "1999-01-13", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "88402408", "name": "M. Yaffe"}, {"authorId": "6239566", "name": "K. Rittinger"}, + {"authorId": "1906416", "name": "S. Volinia"}, {"authorId": "46947956", "name": + "P. Caron"}, {"authorId": "2092260", "name": "A. Aitken"}, {"authorId": "4053866", + "name": "H. Leffers"}, {"authorId": "1958388", "name": "S. Gamblin"}, {"authorId": + "4189482", "name": "S. Smerdon"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "ec75d3d76d188a3091f2ade2c873aca1794c544c", "externalIds": {"MAG": + "1965802234", "DOI": "10.1074/jbc.274.46.32662", "CorpusId": 31837259, "PubMed": + "10551821"}, "corpusId": 31837259, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/ec75d3d76d188a3091f2ade2c873aca1794c544c", + "title": "SYK Is Upstream of Phosphoinositide 3-Kinase in B Cell Receptor + Signaling*", "abstract": "We have recently demonstrated that the D3-phosphoinositide + phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P3) is critical for + producing sustained calcium signals through its role in promoting the function + of TEC family tyrosine kinases such as Bruton''s tyrosine kinase. Although + PtdIns-3,4,5-P3 can potentially be synthesized by any of several types of + phosphoinositide 3-kinases (PI3Ks), B cell receptor (BCR)-induced PtdIns-3,4,5-P3 + production is thought to occur primarily through the activation of the class + Ia (p85/p110) PI3Ks. This process has been proposed to be mediated by an interaction + between the Src family kinase LYN and the p85 subunit of PI3K and/or through + p85 membrane recruitment mediated by CBL and/or CD19. However, calcium signaling + and other PI3K-dependent signals are relatively preserved in a LYN kinase-deficient + B lymphocyte cell line, suggesting that an alternative pathway for PI3K activation + exists. As SYK/ZAP70 kinases are upstream from many BCR-initiated signaling + events, we directly analyzed SYK-dependent accumulation of both PtdIns-3,4,5-P3 + and PtdIns-3,4-P2 in B cell receptor signaling using both dominant negative + and genetic knockout approaches. Both methods indicate that SYK is upstream + of, and necessary for, a significant portion of BCR-induced PtdIns-3,4,5-P3 + production. Whereas CD19 does not appear to be involved in this SYK-dependent + pathway, the SYK substrate CBL is likely involved as the dominant negative + SYK markedly attenuates CBL tyrosine phosphorylation and completely blocks + the BCR-dependent association of CBL with p85 PI3K.", "venue": "Journal of + Biological Chemistry", "year": 1999, "referenceCount": 59, "citationCount": + 192, "influentialCitationCount": 18, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/article/S0021925817465604/pdf", "status": null}, + "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1999-11-12", "journal": {"volume": "274", "pages": "32662 + - 32666", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "6614940", "name": "L. Beitz"}, {"authorId": "6241317", "name": "D. Fruman"}, + {"authorId": "1860005", "name": "T. Kurosaki"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4727704", "name": "A. Scharenberg"}]}, {"paperId": + "f4aadb7f32dc0d83637edcb91092c7c280e229f9", "externalIds": {"MAG": "2077895194", + "DOI": "10.1016/S1097-2765(00)80363-9", "CorpusId": 925317, "PubMed": "10488331"}, + "corpusId": 925317, "publicationVenue": {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", + "name": "Molecules and Cells", "type": "journal", "alternate_names": ["Molecular + Cell", "Mol Cell"], "issn": "1016-8478", "alternate_issns": ["0219-1032", + "1097-2765"], "url": "https://link.springer.com/journal/10059", "alternate_urls": + ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", "http://www.sciencedirect.com/science/journal/10972765", + "http://www.cell.com/molecular-cell/"]}, "url": "https://www.semanticscholar.org/paper/f4aadb7f32dc0d83637edcb91092c7c280e229f9", + "title": "Structural analysis of 14-3-3 phosphopeptide complexes identifies + a dual role for the nuclear export signal of 14-3-3 in ligand binding.", "abstract": + null, "venue": "Molecules and Cells", "year": 1999, "referenceCount": 80, + "citationCount": 500, "influentialCitationCount": 33, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1097276500803639/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1999-08-01", "journal": {"volume": + "4 2", "pages": "\n 153-66\n ", "name": "Molecular cell"}, + "authors": [{"authorId": "6239566", "name": "K. Rittinger"}, {"authorId": + "4299977", "name": "J. Budman"}, {"authorId": "2107782629", "name": "J. Xu"}, + {"authorId": "1906416", "name": "S. Volinia"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4189482", "name": "S. Smerdon"}, {"authorId": + "1958388", "name": "S. Gamblin"}, {"authorId": "88402408", "name": "M. Yaffe"}]}, + {"paperId": "f60ed956df1863612236c5df17315236b2153561", "externalIds": {"MAG": + "2724572059", "DOI": "10.1042/BST027A073C", "CorpusId": 90097503}, "corpusId": + 90097503, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/f60ed956df1863612236c5df17315236b2153561", + "title": "PI 3-KINASE KNOCKOUT MICE: ROLE OF p85\u03b1 IN B CELL DEVELOPMENT + AND PROLIFERATION", "abstract": null, "venue": "", "year": 1999, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "1999-06-01", + "journal": {"volume": "27", "name": "Biochemical Society Transactions"}, "authors": + [{"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "4818618", "name": + "S. Snapper"}, {"authorId": "7777071", "name": "C. Yballe"}, {"authorId": + "1396480779", "name": "F. Mauvais-Jarvis"}, {"authorId": "144391716", "name": + "C. Kahn"}, {"authorId": "31713146", "name": "F. Alt"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "0093753fc77eccd1248d1237709470d5e770eda0", + "externalIds": {"MAG": "2165742826", "DOI": "10.1093/emboj/17.7.1961", "CorpusId": + 7246866, "PubMed": "9524119"}, "corpusId": 7246866, "publicationVenue": {"id": + "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": "journal", + "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", "url": + "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/0093753fc77eccd1248d1237709470d5e770eda0", + "title": "Phosphatidylinositol\u20103,4,5\u2010trisphosphate (PtdIns\u20103,4,5\u2010P3)/Tec + kinase\u2010dependent calcium signaling pathway: a target for SHIP\u2010mediated + inhibitory signals", "abstract": "Tec family non\u2010receptor tyrosine kinases + have been implicated in signal transduction events initiated by cell surface + receptors from a broad range of cell types, including an essential role in + B\u2010cell development. A unique feature of several Tec members among known + tyrosine kinases is the presence of an N\u2010terminal pleckstrin homology + (PH) domain. We directly demonstrate that phosphatidylinositol\u20103,4,5\u2010trisphosphate + (PtdIns\u20103,4,5\u2010P3) interacting with the PH domain acts as an upstream + activation signal for Tec kinases, resulting in Tec kinase\u2010dependent + phospholipase C\u03b3 (PLC\u03b3) tyrosine phosphorylation and inositol trisphosphate + production. In addition, we show that this pathway is blocked when an SH2\u2010containing + inositol phosphatase (SHIP)\u2010dependent inhibitory receptor is engaged. + Together, our results suggest a general mechanism whereby PtdIns\u20103,4,5\u2010P3 + regulates receptor\u2010dependent calcium signals through the function of + Tec kinases.", "venue": "EMBO Journal", "year": 1998, "referenceCount": 75, + "citationCount": 468, "influentialCitationCount": 22, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1170542?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-04-01", "journal": {"volume": "17", "name": "The + EMBO Journal"}, "authors": [{"authorId": "4727704", "name": "A. Scharenberg"}, + {"authorId": "1422641592", "name": "O. El\u2010Hillal"}, {"authorId": "6241317", + "name": "D. Fruman"}, {"authorId": "6614940", "name": "L. Beitz"}, {"authorId": + "121544277", "name": "Zuomei Li"}, {"authorId": "2107932426", "name": "Siqi + Lin"}, {"authorId": "6814491", "name": "I. Gout"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "2156694", "name": "D. Rawlings"}, {"authorId": + "145931354", "name": "J. Kinet"}]}, {"paperId": "0b1b5c2a7057d2d36a07f21db6365afd10f0b875", + "externalIds": {"MAG": "2086955015", "DOI": "10.1074/jbc.273.37.23750", "CorpusId": + 85377279}, "corpusId": 85377279, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/0b1b5c2a7057d2d36a07f21db6365afd10f0b875", + "title": "Phosphoinositide 3-Kinase Regulates Phospholipase C\u03b3-mediated + Calcium Signaling*", "abstract": "It has been demonstrated that the lipid + products of the phosphoinositide 3-kinase (PI3K) can associate with the Src + homology 2 (SH2) domains of specific signaling molecules and modify their + actions. In the current experiments, phosphatidylinositol 3,4,5-trisphosphate + (PtdIns-3,4,5-P3) was found to bind to the C-terminal SH2 domain of phospholipase + C\u03b3 (PLC\u03b3) with an apparent K d of 2.4 \u03bcm and to displace the + C-terminal SH2 domain from the activated platelet-derived growth factor receptor + (PDGFR). To investigate the in vivorelevance of this observation, intracellular + inositol trisphosphate (IP3) generation and calcium release were examined + in HepG2 cells expressing a series of PDGFR mutants that activate PLC\u03b3 + with or without receptor association with PI3K. Coactivation of PLC\u03b3 + and PI3K resulted in an \u223c40% increase in both intracellular IP3generation + and intracellular calcium release as compared with selective activation of + PLC\u03b3. Similarly, the addition of wortmannin or LY294002 to cells expressing + the wild-type PDGFR inhibited the release of intracellular calcium. Thus, + generation of PtdIns-3,4,5-P3by receptor-associated PI3K causes an increase + in IP3production and intracellular calcium release, potentially via enhanced + PtdIns-4,5-P2 substrate availability due to PtdIns-3,4,5-P3-mediated recruitment + of PLC\u03b3 to the lipid bilayer.", "venue": "Journal of Biological Chemistry", + "year": 1998, "referenceCount": 29, "citationCount": 214, "influentialCitationCount": + 15, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/273/37/23750.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "1998-09-11", "journal": {"volume": + "273", "pages": "23750 - 23757", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "4109960", "name": "L. Rameh"}, {"authorId": "3034828", + "name": "S. Rhee"}, {"authorId": "4375980", "name": "K. Spokes"}, {"authorId": + "49161111", "name": "A. Kazlauskas"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "5601835", "name": "L. Cantley"}]}, {"paperId": "0cb94c7b1866632932aaf193fc60a7d252f372bd", + "externalIds": {"MAG": "2142055861", "DOI": "10.1128/MCB.18.2.762", "CorpusId": + 36686515, "PubMed": "9447972"}, "corpusId": 36686515, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/0cb94c7b1866632932aaf193fc60a7d252f372bd", + "title": "Characterization of a Rac1- and RhoGDI-Associated Lipid Kinase Signaling + Complex", "abstract": "ABSTRACT Rho family GTPases regulate a number of cellular + processes, including actin cytoskeletal organization, cellular proliferation, + and NADPH oxidase activation. The mechanisms by which these G proteins mediate + their effects are unclear, although a number of downstream targets have been + identified. The interaction of most of these target proteins with Rho GTPases + is GTP dependent and requires the effector domain. The activation of the NADPH + oxidase also depends on the C terminus of Rac, but no effector molecules that + bind to this region have yet been identified. We previously showed that Rac + interacts with a type I phosphatidylinositol-4-phosphate (PtdInsP) 5-kinase, + independent of GTP. Here we report the identification of a diacylglycerol + kinase (DGK) which also associates with both GTP- and GDP-bound Rac1. In vitro + binding analysis using chimeric proteins, peptides, and a truncation mutant + demonstrated that the C terminus of Rac is necessary and sufficient for binding + to both lipid kinases. The Rac-associated PtdInsP 5-kinase and DGK copurify + by liquid chromatography, suggesting that they bind as a complex to Rac. RhoGDI + also associates with this lipid kinase complex both in vivo and in vitro, + primarily via its interaction with Rac. The interaction between Rac and the + lipid kinases was enhanced by specific phospholipids, indicating a possible + mechanism of regulation in vivo. Given that the products of the PtdInsP 5-kinase + and the DGK have been implicated in several Rac-regulated processes, and they + bind to the Rac C terminus, these lipid kinases may play important roles in + Rac activation of the NADPH oxidase, actin polymerization, and other signaling + pathways.", "venue": "Molecular and Cellular Biology", "year": 1998, "referenceCount": + 68, "citationCount": 157, "influentialCitationCount": 14, "isOpenAccess": + true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc108787?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-02-01", "journal": {"volume": "18", "pages": "762 + - 770", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "4661935", "name": "K. Tolias"}, {"authorId": "153879281", "name": "A. Couvillon"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2972505", "name": + "C. Carpenter"}]}, {"paperId": "1ff2b14a88912d051e31273ae0c4fa72c218c8eb", + "externalIds": {"MAG": "2039185825", "DOI": "10.1074/jbc.273.4.1859", "CorpusId": + 19293669, "PubMed": "9442017"}, "corpusId": 19293669, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/1ff2b14a88912d051e31273ae0c4fa72c218c8eb", + "title": "Regulation of GRP1-catalyzed ADP Ribosylation Factor Guanine Nucleotide + Exchange by Phosphatidylinositol 3,4,5-Trisphosphate*", "abstract": "Cellular + levels of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) are rapidly + elevated in response to activation of growth factor receptor tyrosine kinases. + This polyphosphoinositide binds the pleckstrin homology (PH) domain of GRP1, + a protein that also contains 200 residues with high sequence similarity to + a segment of the yeast Sec7 protein that functions as an ADP ribosylation + exchange factor (ARF) (Klarlund, J., Guilherme, A., Holik, J. J., Virbasius, + J. V., Chawla, A., and Czech, M. P. (1997)Science 275, 1927\u20131930). Here + we show that dioctanoyl PtdIns(3,4,5)P3 binds the PH domain of GRP1 with aK + d = 0.5 \u03bcm, an affinity 2 orders of magnitude greater than dioctanoyl-PtdIns(4,5)P2. + Further, the Sec7 domain of GRP1 is found to catalyze guanine nucleotide exchange + of ARF1 and -5 but not ARF6. Importantly, PtdIns(3,4,5)P3, but not PtdIns(4,5)P2, + markedly enhances the ARF exchange activity of GRP1 in a reaction mixture + containing dimyristoylphosphatidylcholine micelles, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic + acid, and a low concentration of sodium cholate. PtdIns(3,4,5)P3-mediated + ARF nucleotide exchange through GRP1 is selectively blocked by 100 \u03bcm + inositol 1,3,4,5-tetrakisphosphate, which also binds the PH domain of GRP1. + Taken together, these data are consistent with the hypothesis that selective + recruitment of GRP1 to PtdIns(3,4,5)P3 in membranes activates ARF1 and -5, + known regulators of intracellular membrane trafficking.", "venue": "Journal + of Biological Chemistry", "year": 1998, "referenceCount": 29, "citationCount": + 152, "influentialCitationCount": 9, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/273/4/1859.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-01-23", "journal": {"volume": "273", "pages": "1859 + - 1862", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "3593228", "name": "J. Klarlund"}, {"authorId": "4109960", "name": "L. Rameh"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "39917771", "name": + "J. Buxton"}, {"authorId": "2550047", "name": "J. Holik"}, {"authorId": "2196801774", + "name": "Christoper Sakelis"}, {"authorId": "144766253", "name": "V. Patki"}, + {"authorId": "3950323", "name": "S. Corvera"}, {"authorId": "144307657", "name": + "M. Czech"}]}, {"paperId": "23d382b18781cc655c17ca510bc01d027e8b1bca", "externalIds": + {"MAG": "2051627027", "DOI": "10.1006/BBRC.1997.7877", "CorpusId": 84938992}, + "corpusId": 84938992, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/23d382b18781cc655c17ca510bc01d027e8b1bca", + "title": "Extracellular HIV-1 Tat Protein Induces a Rapid and Selective Activation + of Protein Kinase C (PKC)-\u03b1, -\u03f5, and -\u03b6 Isoforms in PC12 Cells", + "abstract": "Abstract The addition in culture of extracellular HIV-1 Tat protein + (0.1-1 nM) to PC12 cells induced a rapid increase of the bulk protein kinase + C (PKC) catalytic activity. Among various PKC isoforms (\u03b1, \u03b2I, \u03b2II, + \u03b4, \u03f5, \u03b7, \u03b8, and \u03b6) expressed in PC12 cells, Tat selectively + stimulated \u03b1, \u03f5, and \u03b6, as judged by activities in immunoprecipitates. + Activation of these isoforms was suppressed by the tyrosine kinase inhibitor + genistein. Moreover, PKC-\u03b6 showed the fastest kinetics of activation + in response to Tat, but PKC-\u03b1 and PKC-\u03f5 showed the highest levels + of activation. PKC-\u03b1 activation was accompanied by a rise of intracellular + IP3, while the PI 3-kinase inhibitors wortmannin and LY294002 suppressed PKC-\u03f5 + activation. Taken together, these findings demonstrate that extracellular + Tat shows a cytokine-like activity in PC12 cells, being able to trigger an + intracellular signalling cascade which involves PKC-\u03b1, -\u03f5, and -\u03b6.", + "venue": "", "year": 1998, "referenceCount": 23, "citationCount": 36, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "1998-01-14", + "journal": {"volume": "242", "pages": "332-337", "name": "Biochemical and + Biophysical Research Communications"}, "authors": [{"authorId": "5619854", + "name": "P. Borgatti"}, {"authorId": "4754758", "name": "G. Zauli"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3996531", "name": "S. Capitani"}]}, + {"paperId": "28cf20508330c0596c5fd4292f4ac39d1d81e27f", "externalIds": {"CorpusId": + 20682842, "PubMed": "10427554"}, "corpusId": 20682842, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/28cf20508330c0596c5fd4292f4ac39d1d81e27f", + "title": "Phosphatidylinositol 4-kinases. Assays and product analysis.", "abstract": + null, "venue": "Methods in molecular biology", "year": 1998, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": null, + "journal": {"volume": "105", "pages": "\n 99-108\n ", "name": + "Methods in molecular biology"}, "authors": [{"authorId": "48408223", "name": + "R. Meyers"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "3fa4ad334602f0b8fd9b63cf880facfeec7e2f14", "externalIds": {"PubMedCentral": + "2132704", "MAG": "2021124770", "DOI": "10.1083/JCB.140.5.1125", "CorpusId": + 18498085, "PubMed": "9490725"}, "corpusId": 18498085, "publicationVenue": + {"id": "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/3fa4ad334602f0b8fd9b63cf880facfeec7e2f14", + "title": "Corequirement of Specific Phosphoinositides and Small GTP-binding + Protein Cdc42 in Inducing Actin Assembly in Xenopus Egg Extracts", "abstract": + "Both phosphoinositides and small GTP-binding proteins of the Rho family have + been postulated to regulate actin assembly in cells. We have reconstituted + actin assembly in response to these signals in Xenopus extracts and examined + the relationship of these pathways. We have found that GTP\u03b3S stimulates + actin assembly in the presence of endogenous membrane vesicles in low speed + extracts. These membrane vesicles are required, but can be replaced by lipid + vesicles prepared from purified phospholipids containing phosphoinositides. + Vesicles containing phosphatidylinositol (4,5) bisphosphate or phosphatidylinositol + (3,4,5) trisphosphate can induce actin assembly even in the absence of GTP\u03b3S. + RhoGDI, a guanine-nucleotide dissociation inhibitor for the Rho family, inhibits + phosphoinositide-induced actin assembly, suggesting the involvement of the + Rho family small G proteins. Using various dominant mutants of these G proteins, + we demonstrate the requirement of Cdc42 for phosphoinositide-induced actin + assembly. Our results suggest that phosphoinositides may act to facilitate + GTP exchange on Cdc42, as well as to anchor Cdc42 and actin nucleation activities. + Hence, both phosphoinositides and Cdc42 are required to induce actin assembly + in this cell-free system.", "venue": "Journal of Cell Biology", "year": 1998, + "referenceCount": 64, "citationCount": 197, "influentialCitationCount": 15, + "isOpenAccess": true, "openAccessPdf": {"url": "http://jcb.rupress.org/content/140/5/1125.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-03-09", "journal": {"volume": "140", "pages": "1125 + - 1136", "name": "The Journal of Cell Biology"}, "authors": [{"authorId": + "2049792", "name": "Le Ma"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2194622", "name": "P. Janmey"}, {"authorId": "40294231", "name": + "M. Kirschner"}]}, {"paperId": "4342ed49c8c83780769189b0874a8ea97fd0992f", + "externalIds": {"MAG": "2067232669", "DOI": "10.1074/jbc.273.36.23126", "CorpusId": + 35784628, "PubMed": "9722541"}, "corpusId": 35784628, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/4342ed49c8c83780769189b0874a8ea97fd0992f", + "title": "Association of Protein Kinase C\u03bc with Type II Phosphatidylinositol + 4-Kinase and Type I Phosphatidylinositol-4-phosphate 5-Kinase*", "abstract": + "Protein kinase C\u03bc (PKC\u03bc), also named protein kinase D, is an unusual + member of the PKC family that has a putative transmembrane domain and pleckstrin + homology domain. This enzyme has a substrate specificity distinct from other + PKC isoforms (Nishikawa, K., Toker, A., Johannes, F. J., Songyang, Z., and + Cantley, L. C. (1997) J. Biol. Chem. 272, 952\u2013960), and its mechanism + of regulation is not yet clear. Here we show that PKC\u03bc forms a complex + in vivo with a phosphatidylinositol 4-kinase and a phosphatidylinositol-4-phosphate + 5-kinase. A region of PKC\u03bc between the amino-terminal transmembrane domain + and the pleckstrin homology domain is shown to be involved in the association + with the lipid kinases. Interestingly, a kinase-dead point mutant of PKC\u03bc + failed to associate with either lipid kinase activity, indicating that autophosphorylation + may be required to expose the lipid kinase interaction domain. Furthermore, + the subcellular distribution of the PKC\u03bc-associated lipid kinases to + the particulate fraction depends on the presence of the amino-terminal region + of PKC\u03bc including the predicted transmembrane region. These results suggest + a novel model in which the non-catalytic region of PKC\u03bc acts as a scaffold + for assembly of enzymes involved in phosphoinositide synthesis at specific + membrane locations.", "venue": "Journal of Biological Chemistry", "year": + 1998, "referenceCount": 38, "citationCount": 96, "influentialCitationCount": + 3, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/273/36/23126.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1998-09-04", "journal": {"volume": "273", "pages": "23126 - 23133", "name": + "The Journal of Biological Chemistry"}, "authors": [{"authorId": "153448781", + "name": "K. Nishikawa"}, {"authorId": "145751285", "name": "A. Toker"}, {"authorId": + "2107344210", "name": "K. Wong"}, {"authorId": "40278978", "name": "P. Marignani"}, + {"authorId": "87883210", "name": "F. Johannes"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "4d75d1d9289e2239e6c12ef7be358f6c881ef6ec", "externalIds": + {"CorpusId": 43669096, "PubMed": "9726983"}, "corpusId": 43669096, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/4d75d1d9289e2239e6c12ef7be358f6c881ef6ec", + "title": "Phosphoinositide 3-kinase regulates phospholipase Cgamma-mediated + calcium signaling.", "abstract": "It has been demonstrated that the lipid + products of the phosphoinositide 3-kinase (PI3K) can associate with the Src + homology 2 (SH2) domains of specific signaling molecules and modify their + actions. In the current experiments, phosphatidylinositol 3,4, 5-trisphosphate + (PtdIns-3,4,5-P3) was found to bind to the C-terminal SH2 domain of phospholipase + Cgamma (PLCgamma) with an apparent Kd of 2.4 microM and to displace the C-terminal + SH2 domain from the activated platelet-derived growth factor receptor (PDGFR). + To investigate the in vivo relevance of this observation, intracellular inositol + trisphosphate (IP3) generation and calcium release were examined in HepG2 + cells expressing a series of PDGFR mutants that activate PLCgamma with or + without receptor association with PI3K. Coactivation of PLCgamma and PI3K + resulted in an approximately 40% increase in both intracellular IP3 generation + and intracellular calcium release as compared with selective activation of + PLCgamma. Similarly, the addition of wortmannin or LY294002 to cells expressing + the wild-type PDGFR inhibited the release of intracellular calcium. Thus, + generation of PtdIns-3,4,5-P3 by receptor-associated PI3K causes an increase + in IP3 production and intracellular calcium release, potentially via enhanced + PtdIns-4, 5-P2 substrate availability due to PtdIns-3,4,5-P3-mediated recruitment + of PLCgamma to the lipid bilayer.", "venue": "Journal of Biological Chemistry", + "year": 1998, "referenceCount": 0, "citationCount": 65, "influentialCitationCount": + 5, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "273 37", "pages": "\n 23750-7\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "4109960", + "name": "L. Rameh"}, {"authorId": "3034828", "name": "S. Rhee"}, {"authorId": + "4375980", "name": "K. Spokes"}, {"authorId": "49161111", "name": "A. Kazlauskas"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5601835", "name": + "L. Cantley"}]}, {"paperId": "5b2c818b41a561a7fff542f48212019e29b7e43d", "externalIds": + {"MAG": "2002388054", "DOI": "10.1016/S1097-2765(00)80279-8", "CorpusId": + 30281368, "PubMed": "9774973"}, "corpusId": 30281368, "publicationVenue": + {"id": "419fc6db-c7c4-4275-80ef-4b89c59bec11", "name": "Molecules and Cells", + "type": "journal", "alternate_names": ["Molecular Cell", "Mol Cell"], "issn": + "1016-8478", "alternate_issns": ["0219-1032", "1097-2765"], "url": "https://link.springer.com/journal/10059", + "alternate_urls": ["http://www.molcells.org/about/sub06.html", "http://www.molecule.org/", + "http://www.sciencedirect.com/science/journal/10972765", "http://www.cell.com/molecular-cell/"]}, + "url": "https://www.semanticscholar.org/paper/5b2c818b41a561a7fff542f48212019e29b7e43d", + "title": "Analysis of an activator:coactivator complex reveals an essential + role for secondary structure in transcriptional activation.", "abstract": + null, "venue": "Molecules and Cells", "year": 1998, "referenceCount": 27, + "citationCount": 162, "influentialCitationCount": 16, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.cell.com/article/S1097276500802798/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Chemistry", "source": "s2-fos-model"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-09-01", "journal": {"volume": "2 3", "pages": "\n 353-9\n ", + "name": "Molecular cell"}, "authors": [{"authorId": "2083623078", "name": + "D. Parker"}, {"authorId": "6256555", "name": "U. Jhala"}, {"authorId": "2238716", + "name": "I. Radhakrishnan"}, {"authorId": "88402408", "name": "M. Yaffe"}, + {"authorId": "35470194", "name": "C. Reyes"}, {"authorId": "2058925746", "name": + "A. Shulman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1697311", "name": "P. Wright"}, {"authorId": "4892627", "name": "M. Montminy"}]}, + {"paperId": "8403a2e0e7f1b3a42c9fec10862e93b25af91eb3", "externalIds": {"MAG": + "2417568262", "DOI": "10.1385/0-89603-491-7:99", "CorpusId": 89544479}, "corpusId": + 89544479, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/8403a2e0e7f1b3a42c9fec10862e93b25af91eb3", + "title": "Phosphatidylinositol 4-Kinases", "abstract": null, "venue": "", + "year": 1998, "referenceCount": 10, "citationCount": 5, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "105", "pages": "99-108", + "name": "Methods of Molecular Biology"}, "authors": [{"authorId": "48408223", + "name": "R. Meyers"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "8f219c96cfe6e51cc6e9f93ab4de7b7afae6a906", "externalIds": {"DOI": "10.1146/annurev.biochem.67.1.481", + "CorpusId": 684244, "PubMed": "9759495"}, "corpusId": 684244, "publicationVenue": + {"id": "9e5ab0fc-a36d-4a05-bc89-12dd1cb12e2b", "name": "Annual Review of Biochemistry", + "type": "journal", "alternate_names": ["Annu Rev Biochem"], "issn": "0066-4154", + "url": "https://www.annualreviews.org/journal/biochem", "alternate_urls": + ["http://www.annualreviews.org/journal/biochem", "http://biochem.annualreviews.org/", + "https://www.annualreviews.org/loi/biochem", "http://intl-biomedical.annualreviews.org/", + "http://arjournals.annualreviews.org/loi/biochem", "http://arjournals.annualreviews.org/loi/biochem?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/8f219c96cfe6e51cc6e9f93ab4de7b7afae6a906", + "title": "Phosphoinositide kinases.", "abstract": "Phosphatidylinositol, a + component of eukaryotic cell membranes, is unique among phospholipids in that + its head group can be phosphorylated at multiple free hydroxyls. Several phosphorylated + derivatives of phosphatidylinositol, collectively termed phosphoinositides, + have been identified in eukaryotic cells from yeast to mammals. Phosphoinositides + are involved in the regulation of diverse cellular processes, including proliferation, + survival, cytoskeletal organization, vesicle trafficking, glucose transport, + and platelet function. The enzymes that phosphorylate phosphatidylinositol + and its derivatives are termed phosphoinositide kinases. Recent advances have + challenged previous hypotheses about the substrate selectivity of different + phosphoinositide kinase families. Here we re-examine the pathways of phosphoinositide + synthesis and the enzymes involved.", "venue": "Annual Review of Biochemistry", + "year": 1998, "referenceCount": 0, "citationCount": 1182, "influentialCitationCount": + 122, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + null, "journal": {"volume": "67", "pages": "\n 481-507\n ", + "name": "Annual review of biochemistry"}, "authors": [{"authorId": "6241317", + "name": "D. Fruman"}, {"authorId": "48408223", "name": "R. Meyers"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "93f46880bcc8daccce8f38ee95b2b18b366f9335", + "externalIds": {"MAG": "2410983068", "DOI": "10.1385/0-89603-392-9:87", "CorpusId": + 38881761, "PubMed": "9523263"}, "corpusId": 38881761, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/93f46880bcc8daccce8f38ee95b2b18b366f9335", + "title": "The use of peptide library for the determination of kinase peptide + substrates.", "abstract": null, "venue": "Methods in molecular biology", "year": + 1998, "referenceCount": 3, "citationCount": 49, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "87", "pages": "\n 87-98\n ", + "name": "Methods in molecular biology"}, "authors": [{"authorId": "6731027", + "name": "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "a67196f0e621a9c575903d80ef7b7004d2219a82", "externalIds": {"MAG": "1980980623", + "DOI": "10.1074/jbc.273.41.26954", "CorpusId": 26866924, "PubMed": "9756944"}, + "corpusId": 26866924, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/a67196f0e621a9c575903d80ef7b7004d2219a82", + "title": "Differential Signaling by the Epidermal Growth Factor-like Growth + Factors Neuregulin-1 and Neuregulin-2*", "abstract": "The neuregulins comprise + a subfamily of epidermal growth factor (EGF)-like growth factors that elicit + diverse cellular responses by activating members of the ErbB family of receptor + tyrosine kinases. Although neuregulin-1 and neuregulin-2 are both binding + ligands for the ErbB3 and ErbB4 receptors, they exhibit distinct biological + activities depending on cellular context. In MDA-MB-468 human mammary tumor + cells, neuregulin-2\u03b2 (NRG2\u03b2) inhibits cell growth, whereas neuregulin-1\u03b2 + (NRG1\u03b2) does not. In these cells, NRG2\u03b2 appears to preferentially + act through the EGF receptor, stimulating receptor tyrosine phosphorylation + and the recruitment of phospholipase C-\u03b3, Cbl, SHP2, and Shc to that + receptor. NRG1\u03b2 preferentially acts through ErbB3 in these cells by stimulating + the tyrosine phosphorylation and recruitment of phosphatidylinositol 3-kinase + and Shc to that receptor. In MDA-MB-453 cells, both NRG1\u03b2 and NRG2\u03b2 + stimulate the tyrosine phosphorylation of the ErbB2 and ErbB3 receptors to + similar extents, but only NRG1\u03b2 potently stimulates morphological changes + consistent with their differentiation. The profiles of SH2 domain-containing + proteins that are efficiently recruited to activated receptors differ for + the two factors. These observations indicate that despite their overlapping + receptor specificity, the neuregulins exhibit distinct biological and biochemical + properties. Since both of these cell lines express only two of the known ErbB + receptors, our results imply that EGF-like ligands might elicit differential + signaling within the context of a single receptor heterodimer.", "venue": + "Journal of Biological Chemistry", "year": 1998, "referenceCount": 41, "citationCount": + 85, "influentialCitationCount": 1, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/273/41/26954.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-10-09", "journal": {"volume": "273", "pages": "26954 + - 26961", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "5252276", "name": "C. S. Crovello"}, {"authorId": "2148764882", "name": "Cary + Lai"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145331905", + "name": "K. Carraway"}]}, {"paperId": "ae1e135a963f6f04bdf3575199523d8fc716137a", + "externalIds": {"MAG": "2072253274", "DOI": "10.1074/jbc.273.29.18040", "CorpusId": + 25563430, "PubMed": "9660759"}, "corpusId": 25563430, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/ae1e135a963f6f04bdf3575199523d8fc716137a", + "title": "Type I Phosphatidylinositol-4-phosphate 5-Kinases Synthesize the + Novel Lipids Phosphatidylinositol 3,5-Bisphosphate and Phosphatidylinositol + 5-Phosphate*", "abstract": "Inositol phospholipids regulate a variety of cellular + processes including proliferation, survival, vesicular trafficking, and cytoskeletal + organization. Recently, two novel phosphoinositides, phosphatidylinositol-3,5-bisphosphate + (PtdIns-3,5-P2) and phosphatidylinositol- 5-phosphate (PtdIns-5-P), have been + shown to exist in cells. PtdIns-3,5-P2, which is regulated by osmotic stress, + appears to be synthesized by phosphorylation of PtdIns-3-P at the D-5 position. + No evidence yet exists for how PtdIns-5-P is produced in cells. Understanding + the regulation of synthesis of these molecules will be important for identifying + their function in cellular signaling. To determine the pathway by which PtdIns-3,5-P2 + and Ptd-Ins-5-P might be synthesized, we tested the ability of the recently + cloned type I PtdIns-4-P 5-kinases (PIP5Ks) \u03b1 and \u03b2 to phosphorylate + PtdIns-3-P and PtdIns at the D-5 position of the inositol ring. We found that + the type I PIP5Ks phosphorylate PtdIns-3-P to form PtdIns-3,5-P2. The identity + of the PtdIns-3,5-P2 product was determined by anion exchange high performance + liquid chromatography analysis and periodate treatment. PtdIns-3,4-P2 and + PtdIns-3,4,5-P3 were also produced from PtdIns-3-P phosphorylation by both + isoforms. When expressed in mammalian cells, PIP5K I\u03b1 and PIP5K I\u03b2 + differed in their ability to synthesize PtdIns-3,5-P2 relative to PtdIns-3,4-P2. + We also found that the type I PIP5Ks phosphorylate PtdIns to produce PtdIns-5-P + and phosphorylate PtdIns-3,4-P2 to produce PtdIns-3,4,5-P3. Our findings suggest + that type I PIP5Ks synthesize the novel phospholipids PtdIns-3,5-P2 and PtdIns-5-P. + The ability of PIP5Ks to produce multiple signaling molecules indicates that + they may participate in a variety of cellular processes.", "venue": "Journal + of Biological Chemistry", "year": 1998, "referenceCount": 34, "citationCount": + 125, "influentialCitationCount": 7, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/273/29/18040.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-07-17", "journal": {"volume": "273", "pages": "18040 + - 18046", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "4661935", "name": "K. Tolias"}, {"authorId": "4109960", "name": "L. Rameh"}, + {"authorId": "2805489", "name": "H. Ishihara"}, {"authorId": "49569359", "name": + "Y. Shibasaki"}, {"authorId": "2118446510", "name": "Jian Chen"}, {"authorId": + "2565299", "name": "G. Prestwich"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2972505", "name": "C. Carpenter"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '239630' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:51 GMT + Via: + - 1.1 50c017c31b8245652ddca43054eeb8de.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - f742SbECnZ_ANUWuec4veZfp19ayIdNvVjFuGL1DrarEbLbiBRb6Kg== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNObxGcWPHcFq2Q= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '239630' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:51 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - f9eaebd1-fc22-4878-a59a-69b814a93b6c + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=700&limit=100 + response: + body: + string: '{"offset": 700, "next": 800, "data": [{"paperId": "cbead89294f23f0ef546103176f2453d7989fc14", + "externalIds": {"CorpusId": 37523925, "PubMed": "9446795"}, "corpusId": 37523925, + "publicationVenue": {"id": "1a9c698b-7fe4-4444-b391-208b4b2326e2", "name": + "Biochemical and Biophysical Research Communications - BBRC", "type": "journal", + "alternate_names": ["Biochem Biophys Res Commun", "Biochemical and Biophysical + Research Communications", "Biochem Biophys Res Commun BBRC"], "issn": "0006-291X", + "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description", + "alternate_urls": ["http://www.idealibrary.com/links/toc/bbrc", "https://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/", + "http://www.sciencedirect.com/science/journal/0006291X"]}, "url": "https://www.semanticscholar.org/paper/cbead89294f23f0ef546103176f2453d7989fc14", + "title": "Extracellular HIV-1 Tat protein induces a rapid and selective activation + of protein kinase C (PKC)-alpha, and -epsilon and -zeta isoforms in PC12 cells.", + "abstract": "The addition in culture of extracellular HIV-1 Tat protein (0.1-1 + nM) to PC12 cells induced a rapid increase of the bulk protein kinase C (PKC) + catalytic activity. Among various PKC isoforms (alpha, beta I, beta II, delta, + epsilon, eta, theta, and zeta) expressed in PC12 cells, Tat selectively stimulated + alpha, epsilon, and zeta, as judged by activities in immunoprecipitates. Activation + of these isoforms was suppressed by the tyrosine kinase inhibitor genistein. + Moreover, PKC-zeta showed the fastest kinetics of activation in response to + Tat, but PKC-alpha and PKC-epsilon showed the highest levels of activation. + PKC-alpha activation was accompanied by a rise of intracellular IP3, while + the PI 3-kinase inhibitors wortmannin and LY294002 suppressed PKC-epsilon + activation. Taken together, these findings demonstrate that extracellular + Tat shows a cytokine-like activity in PC12 cells, being able to trigger an + intracellular signalling cascade which involves PKC-alpha, -epsilon, and -zeta.", + "venue": "Biochemical and Biophysical Research Communications - BBRC", "year": + 1998, "referenceCount": 0, "citationCount": 16, "influentialCitationCount": + 2, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": null, "journal": + {"volume": "242 2", "pages": "\n 332-7\n ", "name": "Biochemical + and biophysical research communications"}, "authors": [{"authorId": "5619854", + "name": "P. Borgatti"}, {"authorId": "4754758", "name": "G. Zauli"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3996531", "name": "S. Capitani"}]}, + {"paperId": "dc05d28dd400db15e6974b1749c398e23e5d9b0f", "externalIds": {"MAG": + "1977674120", "DOI": "10.1038/sj.onc.1201607", "CorpusId": 28452652, "PubMed": + "9484780"}, "corpusId": 28452652, "publicationVenue": {"id": "55bed249-d30f-456b-9d2c-a51dc149cb7a", + "name": "Oncogene", "type": "journal", "issn": "0950-9232", "url": "http://www.nature.com/onc/", + "alternate_urls": ["http://www.nature.com/onc", "http://www.naturesj.com/onc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/dc05d28dd400db15e6974b1749c398e23e5d9b0f", + "title": "Stimulation through the T cell receptor leads to interactions between + SHB and several signaling proteins", "abstract": null, "venue": "Oncogene", + "year": 1998, "referenceCount": 4, "citationCount": 71, "influentialCitationCount": + 6, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1998-02-19", "journal": {"volume": + "16", "pages": "891-901", "name": "Oncogene"}, "authors": [{"authorId": "145515062", + "name": "M. Welsh"}, {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": + "92276956", "name": "J. Frantz"}, {"authorId": "144720430", "name": "T. Tr\u00fcb"}, + {"authorId": "4061084", "name": "K. Reedquist"}, {"authorId": "145168992", + "name": "T. Karlsson"}, {"authorId": "144610439", "name": "M. Miyazaki"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145119394", "name": + "H. Band"}, {"authorId": "4790900", "name": "S. Shoelson"}]}, {"paperId": + "dde5b284129a6a0fbdd5a4e271d0788217db9769", "externalIds": {"MAG": "1988454267", + "DOI": "10.1038/2283", "CorpusId": 7590464, "PubMed": "9783737"}, "corpusId": + 7590464, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/dde5b284129a6a0fbdd5a4e271d0788217db9769", + "title": "A flattened face for membranes", "abstract": null, "venue": "Nature + Structural Biology", "year": 1998, "referenceCount": 8, "citationCount": 6, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Computer Science", "source": "s2-fos-model"}], "publicationTypes": + ["News"], "publicationDate": "1998-10-01", "journal": {"volume": "5", "pages": + "843-845", "name": "Nature Structural Biology"}, "authors": [{"authorId": + "2972505", "name": "C. Carpenter"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "f20c6542f544feb77b003c4d36bd57b8bd725c90", "externalIds": {"MAG": + "2056358535", "DOI": "10.1074/JBC.273.5.2653", "CorpusId": 25089405, "PubMed": + "9446569"}, "corpusId": 25089405, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/f20c6542f544feb77b003c4d36bd57b8bd725c90", + "title": "Activation of P2Y2 Receptors by UTP and ATP Stimulates Mitogen-activated + Kinase Activity through a Pathway That Involves Related Adhesion Focal Tyrosine + Kinase and Protein Kinase C*", "abstract": "We examined downstream signaling + events that followed the exposure of PC12 cells to extracellular ATP and UTP, + and we compared the effects of these P2 receptor agonists with those of growth + factors and other stimuli. Based on early findings, we focused particular + attention on the mitogen-activated protein (MAP) kinase pathway. ATP and/or + UTP produced increases in tyrosine phosphorylation of multiple proteins, including + p42 MAP (ERK2) kinase, related adhesion focal tyrosine kinase (RAFTK) (PYK2, + CAK\u03b2), focal adhesion kinase (FAK), Shc, and protein kinase C\u03b4 (PKC\u03b4). + MAP (ERK2) kinase activity (quantified by substrate phosphorylation) was increased + by UTP, ATP, phorbol 12-myristate 13-acetate, ionomycin, and growth factors. + UTP and ATP were equipotent (EC50 \u223c25 \u03bcm) in stimulating MAP kinase + activity, suggesting that these effects were mediated via the Gi-linked P2Y2 + (P2U) receptor. Consistent with this, the UTP- and ATP-promoted activation + of MAP kinase was diminished in pertussis toxin-treated cells. Treatment of + cells with pertussis toxin also reduced both the UTP-dependent increases in + intracellular calcium ion concentration ([Ca2+] i ) and the tyrosine phosphorylation + of RAFTK. Similarly, when [Ca2+] i elevation was prevented using BAPTA and + EGTA, the activation of MAP kinase by UTP and ionomycin was blocked, and the + tyrosine phosphorylation of RAFTK was reduced. The UTP-promoted increase in + MAP kinase activity was partially reduced in cells in which PKC was down-regulated, + suggesting that both PKC-dependent and PKC-independent pathways were involved. + PKC\u03b4, which increases MAP kinase activity in some systems, became tyrosine-phosphorylated + within 15 s of exposure of cells to ATP or UTP; but epidermal growth factor, + nerve growth factor, and insulin had little effect. UTP also promoted the + association of Shc with Grb2. These results suggest that the P2Y2 receptor-initiated + activation of MAP kinase was dependent on the elevation of [Ca2+] i , involved + the recruitment of Shc and Grb2, and was mediated by RAFTK and PKC.", "venue": + "Journal of Biological Chemistry", "year": 1998, "referenceCount": 45, "citationCount": + 182, "influentialCitationCount": 15, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/273/5/2653.full.pdf", "status": null}, + "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1998-01-30", "journal": {"volume": "273", "pages": "2653 + - 2660", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "4324390", "name": "S. Soltoff"}, {"authorId": "2423275", "name": "H. Avraham"}, + {"authorId": "38846009", "name": "S. Avraham"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "f9e089785a3c2bf41515087fad2a9abda61356b3", "externalIds": + {"MAG": "2154153541", "PubMedCentral": "2141757", "DOI": "10.1083/JCB.140.4.737", + "CorpusId": 168715, "PubMed": "9472028"}, "corpusId": 168715, "publicationVenue": + {"id": "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/f9e089785a3c2bf41515087fad2a9abda61356b3", + "title": "SRPK2: A Differentially Expressed SR Protein-specific Kinase Involved + in Mediating the Interaction and Localization of Pre-mRNA Splicing Factors + in Mammalian Cells", "abstract": "Abstract. Reversible phosphorylation plays + an important role in pre-mRNA splicing in mammalian cells. Two kinases, SR + protein-specific kinase (SRPK1) and Clk/Sty, have been shown to phosphorylate + the SR family of splicing factors. We report here the cloning and characterization + of SRPK2, which is highly related to SRPK1 in sequence, kinase activity, and + substrate specificity. Random peptide selection for preferred phosphorylation + sites revealed a stringent preference of SRPK2 for SR dipeptides, and the + consensus derived may be used to predict potential phosphorylation sites in + candidate arginine and serine-rich (RS) domain\u2013containing proteins. Phosphorylation + of an SR protein (ASF/SF2) by either SRPK1 or 2 enhanced its interaction with + another RS domain\u2013containing protein (U1 70K), and overexpression of + either kinase induced specific redistribution of splicing factors in the nucleus. + These observations likely reflect the function of the SRPK family of kinases + in spliceosome assembly and in mediating the trafficking of splicing factors + in mammalian cells. The biochemical and functional similarities between SRPK1 + and 2, however, are in contrast to their differences in expression. SRPK1 + is highly expressed in pancreas, whereas SRPK2 is highly expressed in brain, + although both are coexpressed in other human tissues and in many experimental + cell lines. Interestingly, SRPK2 also contains a proline-rich sequence at + its NH2 terminus, and a recent study showed that this NH2-terminal sequence + has the capacity to interact with a WW domain protein in vitro. Together, + our studies suggest that different SRPK family members may be uniquely regulated + and targeted, thereby contributing to splicing regulation in different tissues, + during development, or in response to signaling.", "venue": "Journal of Cell + Biology", "year": 1998, "referenceCount": 64, "citationCount": 319, "influentialCitationCount": + 25, "isOpenAccess": true, "openAccessPdf": {"url": "https://rupress.org/jcb/article-pdf/140/4/737/1275188/16515.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1998-02-23", "journal": {"volume": + "140", "pages": "737 - 750", "name": "The Journal of Cell Biology"}, "authors": + [{"authorId": "2113268866", "name": "Huan-You Wang"}, {"authorId": "34503377", + "name": "Wen-chang Lin"}, {"authorId": "88013281", "name": "J. Dyck"}, {"authorId": + "5439166", "name": "J. Yeakley"}, {"authorId": "6731027", "name": "Z. Songyang"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1683422", "name": + "Xiang-Dong Fu"}]}, {"paperId": "0571ff236bcdfbfd24dd3f7c6c5c4ea793e73e61", + "externalIds": {"MAG": "2056270776", "DOI": "10.1126/SCIENCE.276.5320.1848", + "CorpusId": 42804840, "PubMed": "9188528"}, "corpusId": 42804840, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/0571ff236bcdfbfd24dd3f7c6c5c4ea793e73e61", + "title": "Transformation of chicken cells by the gene encoding the catalytic + subunit of PI 3-kinase.", "abstract": "The avian sarcoma virus 16 (ASV 16) + is a retrovirus that induces hemangiosarcomas in chickens. Analysis of the + ASV 16 genome revealed that it encodes an oncogene that is derived from the + cellular gene for the catalytic subunit of phosphoinositide 3-kinase (PI 3-kinase). + The gene is referred to as v-p3k, and like its cellular counterpart c-p3k, + it is a potent transforming gene in cultured chicken embryo fibroblasts (CEFs). + The products of the viral and cellular p3k genes have PI 3-kinase activity. + CEFs transformed with either gene showed elevated levels of phosphatidylinositol + 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and activation + of Akt kinase.", "venue": "Science", "year": 1997, "referenceCount": 26, "citationCount": + 426, "influentialCitationCount": 10, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1997-06-20", "journal": {"volume": "276 5320", "pages": "\n 1848-50\n ", + "name": "Science"}, "authors": [{"authorId": "2158046063", "name": "H. Chang"}, + {"authorId": "1695107", "name": "M. Aoki"}, {"authorId": "6241317", "name": + "D. Fruman"}, {"authorId": "6603909", "name": "K. Auger"}, {"authorId": "5542241", + "name": "A. Bellacosa"}, {"authorId": "4535090", "name": "P. Tsichlis"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6665338", "name": "T. Roberts"}, + {"authorId": "3286670", "name": "P. Vogt"}]}, {"paperId": "064078adf9ab23e93bbe5c0c086b834e459cc05a", + "externalIds": {"MAG": "2080115585", "DOI": "10.1074/jbc.272.2.952", "CorpusId": + 46342228, "PubMed": "8995387"}, "corpusId": 46342228, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/064078adf9ab23e93bbe5c0c086b834e459cc05a", + "title": "Determination of the Specific Substrate Sequence Motifs of Protein + Kinase C Isozymes*", "abstract": "Protein kinase C (PKC) family members play + significant roles in a variety of intracellular signal transduction processes, + but information about the substrate specificities of each PKC family member + is quite limited. In this study, we have determined the optimal peptide substrate + sequence for each of nine human PKC isozymes (\u03b1, \u03b2I, \u03b2II, \u03b3, + \u03b4, \u03b5, \u03b7, \u03bc, and \u03b6) by using an oriented peptide library. + All PKC isozymes preferentially phosphorylated peptides with hydrophobic amino + acids at position +1 carboxyl-terminal of the phosphorylated Ser and basic + residues at position \u22123. All isozymes, except PKC\u03bc, selected peptides + with basic amino acids at positions \u22126, \u22124, and \u22122. PKC\u03b1, + -\u03b2I, -\u03b2II, -\u03b3, and -\u03b7 selected peptides with basic amino + acid at positions +2, +3, and +4, but PKC\u03b4, -\u03b5, -\u03b6, and -\u03bc + preferred peptides with hydrophobic amino acid at these positions. At position + \u22125, the selectivity was quite different among the various isozymes; PKC\u03b1, + -\u03b3, and -\u03b4 selected peptides with Arg at this position while other + PKC isozymes selected hydrophobic amino acids such as Phe, Leu, or Val. Interestingly, + PKC\u03bc showed extreme selectivity for peptides with Leu at this position. + The predicted optimal sequences from position \u22123 to +2 for PKC\u03b1, + -\u03b2I, -\u03b2II, -\u03b3, -\u03b4, and -\u03b7 were very similar to the + endogenous pseudosubstrate sequences of these PKC isozymes, indicating that + these core regions may be important to the binding of corresponding substrate + peptides. Synthetic peptides based on the predicted optimal sequences for + PKC\u03b1, -\u03b2I, -\u03b4, -\u03b6, and -\u03bc were prepared and used + for the determination of Km and Vmax for these isozymes. As judged by Vmax/Km + values, these peptides were in general better substrates of the corresponding + isozymes than those of the other PKC isozymes, supporting the idea that individual + PKC isozymes have distinct optimal substrates. The structural basis for the + selectivity of PKC isozymes is discussed based on residues predicted to form + the catalytic cleft.", "venue": "Journal of Biological Chemistry", "year": + 1997, "referenceCount": 34, "citationCount": 577, "influentialCitationCount": + 21, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/272/2/952.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1997-01-10", "journal": {"volume": "272", "pages": + "952 - 960", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "2060316864", "name": "K. Nishikawa"}, {"authorId": "145751285", "name": "A. + Toker"}, {"authorId": "87883210", "name": "F. Johannes"}, {"authorId": "6731027", + "name": "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "07003144a9d50ece62fe58100386f44f1631c2ac", "externalIds": {"MAG": "2132382863", + "DOI": "10.1074/jbc.272.35.22059", "CorpusId": 35887018, "PubMed": "9268346"}, + "corpusId": 35887018, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/07003144a9d50ece62fe58100386f44f1631c2ac", + "title": "A Comparative Analysis of the Phosphoinositide Binding Specificity + of Pleckstrin Homology Domains*", "abstract": "Pleckstrin homology (PH) and + phosphotyrosine binding (PTB) domains are structurally related regulatory + modules that are present in a variety of proteins involved in signal transduction, + such as kinases, phospholipases, GTP exchange proteins, and adapter proteins. + Initially these domains were shown to mediate protein-protein interactions, + but more recently they were also found to bind phosphoinositides. Most studies + to date have focused on binding of PH domains to phosphatidylinositol (PtdIns)-4-P + and PtdIns-4,5-P2 and have not considered the lipid products of phosphoinositide + 3-kinase: PtdIns-3-P, PtdIns-3,4-P2, and PtdIns-3,4,5-P3. Here we have compared + the phosphoinositide specificity of six different PH domains and the Shc PTB + domain using all five phosphoinositides. We show that the Bruton\u2019s tyrosine + kinase PH domain binds to PtdIns-3,4,5-P3 with higher affinity than to PtdIns-4,5-P2, + PtdIns-3,4-P2 or inositol 1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P4). This + selectivity is decreased by the xid mutation (R28C). Selective binding of + PtdIns-3,4,5-P3 over PtdIns-4,5-P2 or PtdIns-3,4-P2 was also observed for + the amino-terminal PH domain of T lymphoma invasion and metastasis protein + (Tiam-1), the PH domains of Son-of-sevenless (Sos) and, to a lesser extent, + the PH domain of the \u03b2-adrenergic receptor kinase. The oxysterol binding + protein and \u03b2-spectrin PH domains bound PtdIns-3,4,5-P3and PtdIns-4,5-P2 + with similar affinities. PtdIns-3,4,5-P3 and PtdIns-4,5-P2 also bound to the + PTB domain of Shc with similar affinities and lipid binding was competed with + phosphotyrosine (Tyr(P)-containing peptides. These results indicate that distinct + PH domains select for different phosphoinositides.", "venue": "Journal of + Biological Chemistry", "year": 1997, "referenceCount": 42, "citationCount": + 487, "influentialCitationCount": 18, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/272/35/22059.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1997-08-29", "journal": + {"volume": "272", "pages": "22059 - 22066", "name": "The Journal of Biological + Chemistry"}, "authors": [{"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "92556800", "name": "A. Arvidsson"}, {"authorId": "145331905", "name": "K. + Carraway"}, {"authorId": "153879281", "name": "A. Couvillon"}, {"authorId": + "2508043", "name": "G. Rathbun"}, {"authorId": "48345856", "name": "A. Crompton"}, + {"authorId": "5811628", "name": "B. Vanrenterghem"}, {"authorId": "144307657", + "name": "M. Czech"}, {"authorId": "144044294", "name": "K. Ravichandran"}, + {"authorId": "2549319", "name": "S. Burakoff"}, {"authorId": "88869660", "name": + "Dasheng Wang"}, {"authorId": "2145623779", "name": "Ching-shih Chen"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "07e5d5ee463e3f47fc615175f7b1e168ba932dc8", + "externalIds": {"MAG": "2071075259", "DOI": "10.1016/S0092-8674(00)80487-0", + "CorpusId": 14107687, "PubMed": "9428519"}, "corpusId": 14107687, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/07e5d5ee463e3f47fc615175f7b1e168ba932dc8", + "title": "The Structural Basis for 14-3-3:Phosphopeptide Binding Specificity", + "abstract": null, "venue": "Cell", "year": 1997, "referenceCount": 62, "citationCount": + 1561, "influentialCitationCount": 99, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.cell.com/article/S0092867400804870/pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1997-12-26", "journal": {"volume": "91", "pages": "961-971", "name": "Cell"}, + "authors": [{"authorId": "88402408", "name": "M. Yaffe"}, {"authorId": "6239566", + "name": "K. Rittinger"}, {"authorId": "1906416", "name": "S. Volinia"}, {"authorId": + "46947956", "name": "P. Caron"}, {"authorId": "2092260", "name": "A. Aitken"}, + {"authorId": "4053866", "name": "H. Leffers"}, {"authorId": "1958388", "name": + "S. Gamblin"}, {"authorId": "4189482", "name": "S. Smerdon"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "16c6bbcd9592b73b95ba0c05713ea70ee284122b", + "externalIds": {"MAG": "2082494746", "DOI": "10.1093/emboj/16.13.3877", "CorpusId": + 14704532, "PubMed": "9233798"}, "corpusId": 14704532, "publicationVenue": + {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": + "journal", "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", + "url": "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/16c6bbcd9592b73b95ba0c05713ea70ee284122b", + "title": "Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk + to specific SH2 domain proteins in neuronal cells", "abstract": "Eph\u2010related + receptor tyrosine kinases have been implicated in the control of axonal navigation + and fasciculation. To investigate the biochemical mechanisms underlying such + functions, we have expressed the EphB2 receptor (formerly Nuk/Cek5/Sek3) in + neuronal NG108\u201015 cells, and have observed the tyrosine phosphorylation + of multiple cellular proteins upon activation of EphB2 by its ligand, ephrin\u2010B1 + (formerly Elk\u2010L/Lerk2). The activated EphB2 receptor induced the tyrosine + phosphorylation of a 62\u201364 kDa protein (p62dok), which in turn formed + a complex with the Ras GTPase\u2010activating protein (RasGAP) and SH2/SH3 + domain adaptor protein Nck. RasGAP also bound through its SH2 domains to tyrosine\u2010phosphorylated + EphB2 in vitro, and complexed with activated EphB2 in vivo. We have localized + an in vitro RasGAP\u2010binding site to conserved tyrosine residues Y604 and + Y610 in the juxtamembrane region of EphB2, and demonstrated that substitution + of these amino acids abolishes ephrin\u2010B1\u2010induced signalling events + in EphB2\u2010expressing NG108\u201015 cells. These tyrosine residues are + followed by proline at the +3 position, consistent with the binding specificity + of RasGAP SH2 domains determined using a degenerate phosphopeptide library. + These results identify an EphB2\u2010activated signalling cascade involving + proteins that potentially play a role in axonal guidance and control of cytoskeletal + architecture.", "venue": "EMBO Journal", "year": 1997, "referenceCount": 150, + "citationCount": 284, "influentialCitationCount": 17, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1170012?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-07-01", "journal": {"volume": "16", "name": "The + EMBO Journal"}, "authors": [{"authorId": "33801300", "name": "S. Holland"}, + {"authorId": "144667047", "name": "N. Gale"}, {"authorId": "37993016", "name": + "G. Gish"}, {"authorId": "50578252", "name": "R. Roth"}, {"authorId": "6731027", + "name": "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4157754", "name": "M. Henkemeyer"}, {"authorId": "3887512", "name": "G. Yancopoulos"}, + {"authorId": "50999462", "name": "T. Pawson"}]}, {"paperId": "20e8b564070eee34fbfc516733e388a4f371afa1", + "externalIds": {"MAG": "1508167890", "DOI": "10.1038/36621", "CorpusId": 4403301, + "PubMed": "9367159"}, "corpusId": 4403301, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/20e8b564070eee34fbfc516733e388a4f371afa1", + "title": "A new pathway for synthesis of phosphatidylinositol-4,5-bisphosphate", + "abstract": null, "venue": "Nature", "year": 1997, "referenceCount": 17, "citationCount": + 425, "influentialCitationCount": 22, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-11-13", "journal": {"volume": "390", "pages": "192-196", + "name": "Nature"}, "authors": [{"authorId": "4109960", "name": "L. Rameh"}, + {"authorId": "4661935", "name": "K. Tolias"}, {"authorId": "21162853", "name": + "B. Duckworth"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "25cb802bf3009d3184f401b09e076e5145562310", "externalIds": {"MAG": "2043878742", + "DOI": "10.1074/jbc.272.44.27665", "CorpusId": 8280568, "PubMed": "9346906"}, + "corpusId": 8280568, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/25cb802bf3009d3184f401b09e076e5145562310", + "title": "Conditional Inhibition of the Mitogen-activated Protein Kinase Cascade + by Wortmannin", "abstract": "Phosphoinositide (PI) 3-kinase and the mitogen-activated + protein (MAP) kinase cascades are activated by many of the same ligands. Several + groups have reported involvement of PI 3-kinase in the activation of Erk1 + and Erk2, whereas many other groups have shown that activation of Erk1 and + Erk2 is not sensitive to inhibitors of PI 3-kinase such as wortmannin. Here + we show that wortmannin inhibition of the MAP kinase pathway is cell type- + and ligand-specific. Wortmannin blocks platelet-derived growth factor (PDGF)-dependent + activation of Raf-1 and the MAP kinase cascade in Chinese hamster ovary cells, + which have few PDGF receptors, but has no significant effect on Erk activation + in Swiss 3T3 cells, which have high levels of PDGF receptors. However, wortmannin + blocks activation of Erk proteins if Swiss 3T3 cells are stimulated with lower, + physiological levels of PDGF. These results suggest that PI 3-kinase is in + an efficient pathway for activation of MAP kinase, but that MAP kinase can + be stimulated by a redundant pathway when a large number of receptors are + activated. We present evidence that a protein kinase C family member downstream + of phospholipase C\u03b3 is involved in the redundant pathway.", "venue": + "Journal of Biological Chemistry", "year": 1997, "referenceCount": 44, "citationCount": + 227, "influentialCitationCount": 3, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1997-10-31", "journal": {"volume": "272", "pages": "27665 - 27670", "name": + "The Journal of Biological Chemistry"}, "authors": [{"authorId": "21162853", + "name": "B. Duckworth"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "2d5591de2f7d0e9ff757309d1b6daf1ab38ef85e", "externalIds": {"MAG": + "137424080", "DOI": "10.1016/S1040-7952(97)80007-9", "CorpusId": 38760415, + "PubMed": "9344240"}, "corpusId": 38760415, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/2d5591de2f7d0e9ff757309d1b6daf1ab38ef85e", + "title": "Specificity in protein-tyrosine kinase signaling.", "abstract": + null, "venue": "Advances in second messenger and phosphoprotein research", + "year": 1997, "referenceCount": 17, "citationCount": 17, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + null, "journal": {"volume": "31", "pages": "\n 41-8\n ", "name": + "Advances in second messenger and phosphoprotein research"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6731027", "name": "Z. Songyang"}]}, + {"paperId": "3933b3e325552959faa40951ee856e6fbf400b4e", "externalIds": {"MAG": + "2525347699", "CorpusId": 88833992}, "corpusId": 88833992, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/3933b3e325552959faa40951ee856e6fbf400b4e", + "title": "Minireview Blocks Apoptosis", "abstract": ". In vitro, this lipid + can beMontreal Neurological Institute producedby thep170/mCpk-typePI3K that + phosphory-McGill University lates PtdIns-4-P at the D-3 position (Figure 1) + or by aMontreal, Quebec H3A 2B4 kinase that phosphorylates PtdIns-3-P at the + D-4 posi-Canada tion (not shown). Thus, the relative levels of PtdIns-3,4-", + "venue": "", "year": 1997, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["Review"], "publicationDate": + null, "journal": null, "authors": [{"authorId": "50377077", "name": "T. Franke"}, + {"authorId": "2112191705", "name": "D. Kaplan"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "45c0de36133cc86a5c590ab01c9728100dfd71d5", "externalIds": + {"MAG": "2011392056", "DOI": "10.1074/jbc.272.10.6465", "CorpusId": 41813897, + "PubMed": "9045671"}, "corpusId": 41813897, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/45c0de36133cc86a5c590ab01c9728100dfd71d5", + "title": "The Lipid Products of Phosphoinositide 3-Kinase Increase Cell Motility + through Protein Kinase C*", "abstract": "Phosphoinositide 3-kinase has been + implicated as an activator of cell motility in a variety of recent studies, + yet the role of its lipid product, phosphatidylinositol 1,4,5-trisphosphate + (PtdIns-3,4,5-P3), has yet to be elucidated. In this study, three independent + preparations of PtdIns-3,4,5-P3 were found to increase the motility of NIH + 3T3 cells when examined utilizing a microchemotaxis chamber. Dipalmitoyl L-\u03b1-phosphatidyl-D-myo-inositol + 3,4,5-triphosphate (Di-C16-PtdIns-3,4,5-P3) also produced actin reorganization + and membrane ruffling. Cells pretreated with 12-O-tetradecanoylphorbol-13-acetate + to cause down-regulation of protein kinase C (PKC) exhibited complete inhibition + of cell motility induced by Di-C16-PtdIns-3,4,5-P3. These results are consistent + with previous observations that PtdIns-3,4,5-P3 activates Ca2+-independent + PKC isoforms in vitro and in vivo and provide the first demonstration of an + in vivo role for the lipid products of the phosphoinositide 3-kinase. PtdIns-3,4,5-P3 + appears to directly initiate cellular motility via activation of a PKC family + member.", "venue": "Journal of Biological Chemistry", "year": 1997, "referenceCount": + 42, "citationCount": 141, "influentialCitationCount": 5, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/272/10/6465.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-03-07", "journal": {"volume": "272", "pages": "6465 + - 6470", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "144476444", "name": "M. Derman"}, {"authorId": "145751285", "name": "A. Toker"}, + {"authorId": "2999768", "name": "J. Hartwig"}, {"authorId": "4375980", "name": + "K. Spokes"}, {"authorId": "49877841", "name": "J. Falck"}, {"authorId": "2145623779", + "name": "Ching-shih Chen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5601835", "name": "L. Cantley"}]}, {"paperId": "56d780c0edf47e8c5f3ed24829f14e4995310154", + "externalIds": {"MAG": "2006232099", "DOI": "10.1073/PNAS.94.14.7204", "CorpusId": + 23447408, "PubMed": "9207069"}, "corpusId": 23447408, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/56d780c0edf47e8c5f3ed24829f14e4995310154", + "title": "High-affinity binding of the Drosophila Numb phosphotyrosine-binding + domain to peptides containing a Gly-Pro-(p)Tyr motif.", "abstract": "The phosphotyrosine-binding + (PTB) domain is a recently identified protein module that has been characterized + as binding to phosphopeptides containing an NPXpY motif (X = any amino acid). + We describe here a novel peptide sequence recognized by the PTB domain from + Drosophila Numb (dNumb), a protein involved in cell fate determination and + asymmetric cell division during the development of the Drosophila nervous + system. Using a Tyr-oriented peptide library to screen for ligands, the dNumb + PTB domain was found to bind selectively to peptides containing a YIGPYphi + motif (phi represents a hydrophobic residue). A synthetic peptide containing + this sequence bound specifically to the isolated dNumb PTB domain in solution + with a dissociation constant (Kd) of 5.78 +/- 0.74 microM. Interestingly, + the affinity of this peptide for the dNumb PTB domain was increased (Kd = + 1.41 +/- 0.10 microM) when the second tyrosine in the sequence was phosphorylated. + Amino acid substitution studies of the phosphopeptide demonstrated that a + core motif of sequence GP(p)Y is required for high-affinity binding to the + dNumb PTB domain. Nuclear magnetic resonance experiments performed on isotopically + labeled protein complexed with either Tyr- or pTyr-containing peptides suggest + that the same set of amino acids in the dNumb PTB domain is involved in binding + both phosphorylated and nonphosphorylated forms of the peptide. The in vitro + selectivity of the dNumb PTB domain is therefore markedly different from those + of the Shc and IRS-1 PTB domains, in that it interacts preferentially with + a GP(p)Y motif, rather than NPXpY, and does not absolutely require ligand + phosphorylation for binding. Our results suggest that the PTB domain is a + versatile protein module, capable of exhibiting varied binding specificities.", + "venue": "Proceedings of the National Academy of Sciences of the United States + of America", "year": 1997, "referenceCount": 33, "citationCount": 66, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc23792?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-07-08", "journal": {"volume": "94 14", "pages": "\n 7204-9\n ", + "name": "Proceedings of the National Academy of Sciences of the United States + of America"}, "authors": [{"authorId": "3355322", "name": "S. C. Li"}, {"authorId": + "6731027", "name": "Z. Songyang"}, {"authorId": "47486540", "name": "S. Vincent"}, + {"authorId": "48706514", "name": "C. Zwahlen"}, {"authorId": "34735160", "name": + "S. Wiley"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4451948", + "name": "L. Kay"}, {"authorId": "1398007359", "name": "J. Forman-Kay"}, {"authorId": + "50999462", "name": "T. Pawson"}]}, {"paperId": "58e5eb18283eeb15eb4c13e0700c82239b5c41fb", + "externalIds": {"MAG": "2033801757", "DOI": "10.1016/S0092-8674(00)81883-8", + "CorpusId": 2574667, "PubMed": "9038334"}, "corpusId": 2574667, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/58e5eb18283eeb15eb4c13e0700c82239b5c41fb", + "title": "PI3K: Downstream AKTion Blocks Apoptosis", "abstract": null, "venue": + "Cell", "year": 1997, "referenceCount": 24, "citationCount": 1773, "influentialCitationCount": + 62, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867400818838/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "1997-02-21", "journal": + {"volume": "88", "pages": "435-437", "name": "Cell"}, "authors": [{"authorId": + "50377077", "name": "T. Franke"}, {"authorId": "32389352", "name": "D. Kaplan"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "6a231c60427ef7d51c7b7dff1c37463b6382b32d", + "externalIds": {"MAG": "2009857536", "DOI": "10.1073/PNAS.94.7.3016", "CorpusId": + 14768592, "PubMed": "9096338"}, "corpusId": 14768592, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/6a231c60427ef7d51c7b7dff1c37463b6382b32d", + "title": "Identification of a novel pathway important for proliferation and + differentiation of primary erythroid progenitors.", "abstract": "Homodimerization + of the erythropoietin (EPO) receptor (EPO-R) in response to EPO binding transiently + activates the receptor-associated protein tyrosine kinase JAK2. Tyrosine phosphorylation + of the EPO-R creates \"docking sites\" for SH2 domain(s) in signaling molecules + such as the protein tyrosine phosphatases SH-PTP1 and SH-PTP2, phosphoinositide + 3-kinase (PI3 kinase), and STAT5. However, little is known about the specific + intracellular signals essential for proliferation and differentiation of erythroid + progenitors. Here we show that an EPO-R containing only one cytosolic (phospho)tyrosine + residue, Y479, induces a signal transduction pathway sufficient for proliferation + and differentiation of fetal liver progenitors of erythroid colony-forming + units from EPO-R(-/-) mice as well as for proliferation of cultured hematopoietic + cells. This cascade involves sequential EPO-induced recruitment of PI3 kinase + to the EPO-R and activation of mitogen-activated protein kinase activity, + independent of the Shc/Grb2-adapter pathway and of STAT5. Protein kinase C + epsilon may be one of the mediators connecting PI3 kinase with the mitogen-activated + protein kinase signaling cascade. Our results identify a signaling cascade + important in vivo for erythroid cell proliferation and differentiation.", + "venue": "Proceedings of the National Academy of Sciences of the United States + of America", "year": 1997, "referenceCount": 60, "citationCount": 196, "influentialCitationCount": + 4, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc20314?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1997-04-01", "journal": {"volume": + "94 7", "pages": "\n 3016-21\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "1906951", "name": "U. Klingm\u00fcller"}, {"authorId": "2107348244", + "name": "H. Wu"}, {"authorId": "8691674", "name": "J. G. Hsiao"}, {"authorId": + "145751285", "name": "A. Toker"}, {"authorId": "21162853", "name": "B. Duckworth"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "7757698", "name": + "H. Lodish"}]}, {"paperId": "76b361e8530cdc8a370fe10fdbc066f270c695a0", "externalIds": + {"MAG": "1650807611", "DOI": "10.1038/36442", "CorpusId": 4348611, "PubMed": + "9367147"}, "corpusId": 4348611, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/76b361e8530cdc8a370fe10fdbc066f270c695a0", + "title": "Apoptosis: A Bad kinase makes good", "abstract": null, "venue": + "Nature", "year": 1997, "referenceCount": 1, "citationCount": 196, "influentialCitationCount": + 7, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["News"], "publicationDate": "1997-11-13", + "journal": {"volume": "390", "pages": "116-117", "name": "Nature"}, "authors": + [{"authorId": "50377077", "name": "T. Franke"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "7a55b4e72f67f9aef7769436ac09945948be5809", "externalIds": + {"MAG": "1999922223", "DOI": "10.1074/jbc.272.20.13419", "CorpusId": 29943100, + "PubMed": "9148966"}, "corpusId": 29943100, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/7a55b4e72f67f9aef7769436ac09945948be5809", + "title": "The SH3 Domain of Amphiphysin Binds the Proline-rich Domain of Dynamin + at a Single Site That Defines a New SH3 Binding Consensus Sequence*", "abstract": + "Amphiphysin is an SH3 domain-containing neuronal protein that is highly concentrated + in nerve terminals where it interacts via its SH3 domain with dynamin I, a + GTPase implicated in synaptic vesicle endocytosis. We show here that the SH3 + domain of amphiphysin, but not a mutant SH3 domain, bound with high affinity + to a single site in the long proline-rich region of human dynamin I, that + this site was distinct from the binding sites for other SH3 domains, and that + the mutation of two adjacent amino acids in dynamin I was sufficient to abolish + binding. The dynamin I sequence critically required for amphiphysin binding + (PSRPNR) fits in the novel SH3 binding consensus identified for the SH3 domain + of amphiphysin via a combinatorial peptide library approach: PXRPXR(H)R(H). + Our data demonstrate that the long proline-rich stretch present in dynamin + I contained multiple SH3 domain binding sites that recognize interacting proteins + with high specificity.", "venue": "Journal of Biological Chemistry", "year": + 1997, "referenceCount": 38, "citationCount": 239, "influentialCitationCount": + 20, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/272/20/13419.full.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1997-05-16", "journal": {"volume": + "272", "pages": "13419 - 13425", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "6943642", "name": "D. Grabs"}, {"authorId": "5444300", + "name": "V. Slepnev"}, {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": + "2053464291", "name": "C. David"}, {"authorId": "2071053200", "name": "M. + Lynch"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3318861", + "name": "P. De Camilli"}]}, {"paperId": "842663edc91d5ce9bfb3ace965a0398c9b1f1622", + "externalIds": {"MAG": "2140194302", "DOI": "10.1093/emboj/16.9.2240", "CorpusId": + 12817757, "PubMed": "9171339"}, "corpusId": 12817757, "publicationVenue": + {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", "name": "EMBO Journal", "type": + "journal", "alternate_names": ["The EMBO Journal", "EMBO J"], "issn": "0261-4189", + "url": "http://embojournal.npgjournals.com/", "alternate_urls": ["http://emboj.embopress.org/"]}, + "url": "https://www.semanticscholar.org/paper/842663edc91d5ce9bfb3ace965a0398c9b1f1622", + "title": "Regulatory interactions in the recognition of endocytic sorting + signals by AP\u20102 complexes", "abstract": "Many plasma membrane proteins + destined for endocytosis are concentrated into clathrin\u2010coated pits through + the recognition of a tyrosine\u2010based motif in their cytosolic domains + by an adaptor (AP\u20102) complex. The \u03bc2 subunit of isolated AP\u20102 + complexes binds specifically, but rather weakly, to proteins bearing the tyrosine\u2010based + signal. We now demonstrate, using peptides with a photoreactive probe, that + this binding is strengthened significantly when the AP\u20102 complex is present + in clathrin coats, indicating that there is cooperativity between receptor\u2013AP\u20102 + interactions and coat formation. Phosphoinositides with a phosphate at the + D\u20103 position of the inositol ring, but not other isomers, also increase + the affinity of the AP\u20102 complex for the tyrosine\u2010based motif. AP\u20102 + is the first protein known (in any context) to interact with phosphatidylinositol + 3\u2010phosphate. Our findings indicate that receptor recruitment can be coupled + to clathrin coat assembly and suggest a mechanism for regulation of membrane + traffic by lipid products of phosphoinositide 3\u2010kinases.", "venue": "EMBO + Journal", "year": 1997, "referenceCount": 157, "citationCount": 232, "influentialCitationCount": + 10, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1169826?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-05-01", "journal": {"volume": "16", "name": "The + EMBO Journal"}, "authors": [{"authorId": "2053078190", "name": "I. Rapoport"}, + {"authorId": "144610439", "name": "M. Miyazaki"}, {"authorId": "6576021", + "name": "W. Boll"}, {"authorId": "21162853", "name": "B. Duckworth"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4790900", "name": "S. Shoelson"}, + {"authorId": "4218577", "name": "T. Kirchhausen"}]}, {"paperId": "8eec8d2813f6955a670e804df4ef0b8cf74ed4a4", + "externalIds": {"MAG": "1993205500", "DOI": "10.1073/PNAS.94.21.11345", "CorpusId": + 17086418, "PubMed": "9326612"}, "corpusId": 17086418, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/8eec8d2813f6955a670e804df4ef0b8cf74ed4a4", + "title": "Interleukin 3-dependent survival by the Akt protein kinase.", "abstract": + "Interleukin 3 (IL-3)-dependent survival of hematopoietic cells is known to + rely on the activity of multiple signaling pathways, including a pathway leading + to activation of phosphoinositide 3-kinase (PI 3-kinase), and protein kinase + Akt is a direct target of PI 3-kinase. We find that Akt kinase activity is + rapidly induced by the cytokine IL-3, suggesting a role for Akt in PI 3-kinase-dependent + signaling in hematopoetic cells. Dominant-negative mutants of Akt specifically + block Akt activation by IL-3 and interfere with IL-3-dependent proliferation. + Overexpression of Akt or oncogenic v-akt protects 32D cells from apoptosis + induced by IL-3 withdrawal. Apoptosis after IL-3 withdrawal is accelerated + by expression of dominant-negative mutants of Akt, indicating that a functional + Akt signaling pathway is necessary for cell survival mediated by the cytokine + IL-3. Thus Akt appears to be an important mediator of anti-apoptotic signaling + in this system.", "venue": "Proceedings of the National Academy of Sciences + of the United States of America", "year": 1997, "referenceCount": 69, "citationCount": + 398, "influentialCitationCount": 15, "isOpenAccess": true, "openAccessPdf": + {"url": "https://www.pnas.org/content/pnas/94/21/11345.full.pdf", "status": + null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-10-14", "journal": {"volume": "94 21", "pages": "\n 11345-50\n ", + "name": "Proceedings of the National Academy of Sciences of the United States + of America"}, "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, + {"authorId": "144293138", "name": "D. Baltimore"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "32389352", "name": "D. Kaplan"}, {"authorId": + "50377077", "name": "T. Franke"}]}, {"paperId": "9630b575c263be3b36b99c88768791bb60e2e4ab", + "externalIds": {"MAG": "2046208810", "DOI": "10.1111/J.1432-1033.1997.T01-1-00433.X", + "CorpusId": 25708621, "PubMed": "9208935"}, "corpusId": 25708621, "publicationVenue": + {"id": "9b975127-186d-4b72-b03c-7b63988f3aec", "name": "European Journal of + Biochemistry", "type": "journal", "alternate_names": ["Eur J Biochem"], "issn": + "0014-2956", "alternate_issns": ["1432-1033"], "url": "https://onlinelibrary.wiley.com/journal/17424658", + "alternate_urls": ["http://www.ejbiochem.org/", "http://www.febsjournal.org/"]}, + "url": "https://www.semanticscholar.org/paper/9630b575c263be3b36b99c88768791bb60e2e4ab", + "title": "Sequence specificity of C-terminal Src kinase (CSK)--a comparison + with Src-related kinases c-Fgr and Lyn.", "abstract": "An eicosapeptide encompassing + the C-terminal tail of c-Src (Tyr527) which is conserved in most Src-related + protein kinases, is phosphorylated by C-terminal Src kinase (CSK) and by the + two Src-related protein kinases c-Fgr and Lyn, with similar kinetic constants. + Two related peptides reproducing the C-terminal segments of c-Src mutants + defective in CSK phosphorylation [MacAuley, A., Okada, M., Nada, S., Nakagawa, + H. & Cooper, J. A. (1993) Oncogene 8, 117-124] AFLEDSCTGTEPLYQRGENL (mutant + number 28) and AFLEDNFTGTKPQYHPGENL (mutant number 29), proved a better and + a much worse substrates, respectively than the wild-type peptide, with either + CSK or the two Src kinases. By changing individual residues in the best peptide + substrate, it was shown that the main element responsible for its improved + phosphorylation is leucine at position -1 (instead of glutamine), while lysine + at position -3 (instead of glutamate) has a detrimental effect, possibly accounting + for the negligible phosphorylation of peptide derived from mutant number 29. + By contrast to most peptide substrates, including the Src C-terminal peptides, + which exhibit relatively high K(m) values, a polyoma-virus-middle-T-antigen-(mT)-derived + peptide with tyrosine embedded in a highly hydrophobic sequence (EEEPQFEEIPIYLELLP) + exhibits with CSK a quite low K(m) value (63 microM). Consistent with this, + the optimal sequence selected by CSK in an oriented peptide library is XXXIYMFFF. + This is different from sequences selected by Lyn (DEEIYEELX) and c-Fgr (XEEIYGIFF), + although they all share a high selection for a hydrophobic residue at n-1. + In sharp contrast, TPKIIB/p38syk, related to the catalytic domain of p72syk, + selects acidic residues at nearly all positions, n-1 included. These data + support the notion that the features determining the specific phosphorylation + of the C-terminal tyrosine residue of Src do not reside in the primary structure + surrounding the target tyrosine. They also show that this site does not entirely + fulfil the optimal consensus sequence recognized by CSK, disclosing the possibility + that as yet unrecognized CSK targets structurally unrelated to the C-terminal + tyrosine residue of Src kinases may exist.", "venue": "European Journal of + Biochemistry", "year": 1997, "referenceCount": 51, "citationCount": 25, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1432-1033.1997.t01-1-00433.x", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1997-06-01", "journal": {"volume": "246 2", + "pages": "\n 433-9\n ", "name": "European journal of biochemistry"}, + "authors": [{"authorId": "2709754", "name": "M. Ruzzene"}, {"authorId": "6731027", + "name": "Z. Songyang"}, {"authorId": "33761180", "name": "O. Marin"}, {"authorId": + "1397947088", "name": "A. Donella\u2010Deana"}, {"authorId": "6573879", "name": + "A. Brunati"}, {"authorId": "145585360", "name": "B. Guerra"}, {"authorId": + "3971054", "name": "P. Agostinis"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2079990", "name": "L. Pinna"}]}, {"paperId": "992fb58aa10ba00c6b4bfd80331c9589d4f1f9fd", + "externalIds": {"MAG": "1568605582", "DOI": "10.1038/42648", "CorpusId": 4347728, + "PubMed": "9192891"}, "corpusId": 4347728, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/992fb58aa10ba00c6b4bfd80331c9589d4f1f9fd", + "title": "Signalling through the lipid products of phosphoinositide-3-OH kinase", + "abstract": null, "venue": "Nature", "year": 1997, "referenceCount": 46, "citationCount": + 1398, "influentialCitationCount": 51, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "1997-06-12", "journal": {"volume": "387", "pages": "673-676", + "name": "Nature"}, "authors": [{"authorId": "145751285", "name": "A. Toker"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "d81b0874f40b7f32378b384f336d701f766a9883", + "externalIds": {"MAG": "2975658554", "DOI": "10.2210/pdb1pbw/pdb", "CorpusId": + 204136780}, "corpusId": 204136780, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d81b0874f40b7f32378b384f336d701f766a9883", + "title": "STRUCTURE OF BCR-HOMOLOGY (BH) DOMAIN", "abstract": null, "venue": + "", "year": 1997, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "1997-03-12", "journal": {"volume": "", "name": ""}, "authors": [{"authorId": + "4370379", "name": "A. Musacchio"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2150243975", "name": "S. Harrison"}]}, {"paperId": "d9170821d47371ce2c5848f8ef544a591b14a634", + "externalIds": {"MAG": "2126043496", "DOI": "10.1126/SCIENCE.278.5345.1957", + "CorpusId": 46210419, "PubMed": "9395400"}, "corpusId": 46210419, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/d9170821d47371ce2c5848f8ef544a591b14a634", + "title": "Sequence-specific and phosphorylation-dependent proline isomerization: + a potential mitotic regulatory mechanism.", "abstract": "Pin1 is an essential + and conserved mitotic peptidyl-prolyl isomerase (PPIase) that is distinct + from members of two other families of conventional PPIases, cyclophilins and + FKBPs (FK-506 binding proteins). In response to their phosphorylation during + mitosis, Pin1 binds and regulates members of a highly conserved set of proteins + that overlaps with antigens recognized by the mitosis-specific monoclonal + antibody MPM-2. Pin1 is here shown to be a phosphorylation-dependent PPIase + that specifically recognizes the phosphoserine-proline or phosphothreonine-proline + bonds present in mitotic phosphoproteins. Both Pin1 and MPM-2 selected similar + phosphorylated serine-proline-containing peptides, providing the basis for + the specific interaction between Pin1 and MPM-2 antigens. Pin1 preferentially + isomerized proline residues preceded by phosphorylated serine or threonine + with up to 1300-fold selectivity compared with unphosphorylated peptides. + Pin1 may thus regulate mitotic progression by catalyzing sequence-specific + and phosphorylation-dependent proline isomerization.", "venue": "Science", + "year": 1997, "referenceCount": 27, "citationCount": 783, "influentialCitationCount": + 41, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1997-12-12", "journal": {"volume": + "278 5345", "pages": "\n 1957-60\n ", "name": "Science"}, + "authors": [{"authorId": "88402408", "name": "M. Yaffe"}, {"authorId": "6092366", + "name": "M. Schutkowski"}, {"authorId": "47767216", "name": "M. Shen"}, {"authorId": + "40403105", "name": "X. Z. Zhou"}, {"authorId": "5090761", "name": "P. Stukenberg"}, + {"authorId": "49127913", "name": "J. Rahfeld"}, {"authorId": "2107782629", + "name": "J. Xu"}, {"authorId": "145526176", "name": "J. Kuang"}, {"authorId": + "40294231", "name": "M. Kirschner"}, {"authorId": "1693102", "name": "G. Fischer"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2118247016", + "name": "K. Lu"}]}, {"paperId": "dee1bba8217028c0b88731f1deb621437ceb944e", + "externalIds": {"MAG": "2078400325", "DOI": "10.1074/jbc.272.52.33140", "CorpusId": + 8179761, "PubMed": "9407100"}, "corpusId": 8179761, "publicationVenue": {"id": + "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological Chemistry", + "type": "journal", "alternate_names": ["J Biological Chem"], "issn": "0021-9258", + "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", "alternate_urls": + ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": "https://www.semanticscholar.org/paper/dee1bba8217028c0b88731f1deb621437ceb944e", + "title": "The Cbl Phosphotyrosine-binding Domain Selects a D(N/D)XpY Motif + and Binds to the Tyr292Negative Regulatory Phosphorylation Site of ZAP-70*", + "abstract": "The Cbl protooncogene product has emerged as a novel negative + regulator of receptor and non-receptor tyrosine kinases through currently + undefined mechanisms. Therefore, determining how Cbl physically interacts + with tyrosine kinases is of substantial interest. We recently identified a + phosphotyrosine binding (PTB) domain residing within the N-terminal transforming + region of Cbl (Cbl-N), which mediated direct binding to ZAP-70 tyrosine kinase. + Here, we have screened a degenerate phosphopeptide library and show that the + Cbl-PTB domain selects a D(N/D)XpY motif, reminiscent of but distinct from + the NPXpY motif recognized by the PTB domains of Shc and IRS-1/2. A phosphopeptide + predicted by this motif and corresponding to the in vivo negative regulatory + phosphorylation site of ZAP-70 (Tyr(P)292) specifically inhibited binding + of ZAP-70 to Cbl-N. A ZAP-70/Y292F mutant failed to bind to Cbl-N, whereas + a D290A mutant resulted in a 64% decrease in binding, confirming the importance + of the Tyr(P) and Y-2 residues in Cbl-PTB domain recognition. Finally the + ZAP-70/Y292F mutant also failed to associate with Cbl-N or full-length Cbl + in vivo. These results identify a potential Cbl-PTB domain-dependent role + for Cbl in the negative regulation of ZAP-70 and predict potential Cbl-PTB + domain binding sites on other protein tyrosine kinases known to interact with + Cbl.", "venue": "Journal of Biological Chemistry", "year": 1997, "referenceCount": + 48, "citationCount": 228, "influentialCitationCount": 9, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/272/52/33140.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1997-12-26", "journal": {"volume": "272", "pages": "33140 - 33144", "name": + "The Journal of Biological Chemistry"}, "authors": [{"authorId": "5236504", + "name": "M. Lupher"}, {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": + "4790900", "name": "S. Shoelson"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "145119394", "name": "H. Band"}]}, {"paperId": "df7a2e7ecd0deff9114f7b42f82603fded211188", + "externalIds": {"MAG": "1988594478", "DOI": "10.1126/SCIENCE.275.5296.73", + "CorpusId": 8726366, "PubMed": "8974395"}, "corpusId": 8726366, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/df7a2e7ecd0deff9114f7b42f82603fded211188", + "title": "Recognition of Unique Carboxyl-Terminal Motifs by Distinct PDZ Domains", + "abstract": "The oriented peptide library technique was used to investigate + the peptide-binding specificities of nine PDZ domains. Each PDZ domain selected + peptides with hydrophobic residues at the carboxyl terminus. Individual PDZ + domains selected unique optimal motifs defined primarily by the carboxyl terminal + three to seven residues of the peptides. One family of PDZ domains, including + those of the Discs Large protein, selected peptides with the consensus motif + Glu-(Ser/Thr)-Xxx-(Val/Ile) (where Xxx represents any amino acid) at the carboxyl + terminus. In contrast, another family of PDZ domains, including those of LIN-2, + p55, and Tiam-1, selected peptides with hydrophobic or aromatic side chains + at the carboxyl terminal three residues. On the basis of crystal structures + of the PSD-95-3 PDZ domain, the specificities observed with the peptide library + can be rationalized.", "venue": "Science", "year": 1997, "referenceCount": + 24, "citationCount": 1390, "influentialCitationCount": 64, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-01-03", "journal": {"volume": "275", "pages": "73 + - 77", "name": "Science"}, "authors": [{"authorId": "6731027", "name": "Z. + Songyang"}, {"authorId": "39814834", "name": "A. Fanning"}, {"authorId": "2084646749", + "name": "C. Fu"}, {"authorId": "2107782629", "name": "J. Xu"}, {"authorId": + "6428784", "name": "S. Marfatia"}, {"authorId": "3739451", "name": "A. Chishti"}, + {"authorId": "48345856", "name": "A. Crompton"}, {"authorId": "10427932", + "name": "A. Chan"}, {"authorId": "1786654", "name": "J. Anderson"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "e0badc8710740a515ed591a871a14d1c30265117", + "externalIds": {"MAG": "2094068658", "DOI": "10.1126/SCIENCE.275.5300.665", + "CorpusId": 31186873, "PubMed": "9005852"}, "corpusId": 31186873, "publicationVenue": + {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", "name": "Science", "type": + "journal", "issn": "0193-4511", "alternate_issns": ["0036-8075"], "url": "https://www.jstor.org/journal/science", + "alternate_urls": ["https://www.sciencemag.org/", "http://www.sciencemag.org/", + "http://www.jstor.org/journals/00368075.html", "http://www.sciencemag.org/archive/"]}, + "url": "https://www.semanticscholar.org/paper/e0badc8710740a515ed591a871a14d1c30265117", + "title": "Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate", + "abstract": "The regulation of the serine-threonine kinase Akt by lipid products + of phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity + was found to correlate with the amount of phosphatidylinositol-3,4-bisphosphate + (PtdIns-3,4-P2) in vivo, and synthetic PtdIns-3,4-P2 activated Akt both in + vitro and in vivo. Binding of PtdIns-3,4-P2 occurred within the Akt pleckstrin + homology (PH) domain and facilitated dimerization of Akt. Akt mutated in the + PH domain was not activated by PI 3-kinase in vivo or by PtdIns-3,4-P2 in + vitro, and it was impaired in binding to PtdIns-3,4-P2. Examination of the + binding to other phosphoinositides revealed that they bound to the Akt PH + domain with much lower affinity than did PtdIns-3,4-P2 and failed to increase + Akt activity. Thus, Akt is apparently regulated by the direct interaction + of PtdIns-3,4-P2 with the Akt PH domain.", "venue": "Science", "year": 1997, + "referenceCount": 13, "citationCount": 1568, "influentialCitationCount": 90, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1997-01-31", "journal": {"volume": + "275", "pages": "665 - 668", "name": "Science"}, "authors": [{"authorId": + "50377077", "name": "T. Franke"}, {"authorId": "32389352", "name": "D. Kaplan"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "145751285", "name": + "A. Toker"}]}, {"paperId": "eb924acd1f5b93abe75ca33ebc6934f09cf3a1fc", "externalIds": + {"MAG": "2078411393", "DOI": "10.1074/jbc.272.7.4384", "CorpusId": 33901540, + "PubMed": "9020160"}, "corpusId": 33901540, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/eb924acd1f5b93abe75ca33ebc6934f09cf3a1fc", + "title": "Cloning and Characterization of a Wortmannin-sensitive Human Phosphatidylinositol + 4-Kinase*", "abstract": "Phosphatidylinositol (PtdIns) 4-kinases catalyze + the synthesis of PtdIns-4-P, the immediate precursor of PtdIns-4,5-P2. Here + we report the cloning of a novel, ubiquitously expressed PtdIns 4-kinase (PI4K\u03b2). + The 2.4-kilobase pair cDNA encodes a putative translation product of 801 amino + acids which shows greatest homology to the yeast PIK1 gene. The recombinant + protein exhibits lipid kinase activity when expressed in Escherichia coli, + and specific antibodies recognize a 110-kDa PtdIns 4-kinase in cell lysates. + The biochemical properties of PI4K\u03b2 are characteristic of a type III + enzyme. Interestingly, both recombinant PI4K\u03b2 and the endogenous protein + are inhibited by 150 nM wortmannin, suggesting that we have cloned the previously + described PtdIns 4-kinase that is responsible for regulating the synthesis + of agonist-sensitive pools of polyphosphoinositides (Nakanishi, S., Catt, + J. K., and Balla, T. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 5317-5321).", + "venue": "Journal of Biological Chemistry", "year": 1997, "referenceCount": + 50, "citationCount": 167, "influentialCitationCount": 7, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925819673060/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1997-02-14", "journal": {"volume": + "272", "pages": "4384 - 4390", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "48408223", "name": "R. Meyers"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "fb968f8f961b964d00cf434026dcdef0d404e367", + "externalIds": {"MAG": "1998749044", "DOI": "10.1074/jbc.272.20.13236", "CorpusId": + 23850268, "PubMed": "9148941"}, "corpusId": 23850268, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/fb968f8f961b964d00cf434026dcdef0d404e367", + "title": "Subcellular Locations of Phosphatidylinositol 4-Kinase Isoforms*", + "abstract": "Phosphatidylinositol (PtdIns) 4-kinase catalyzes the synthesis + of PtdIns-4-P, the precursor of an array of lipid second messengers generated + by additional phosphorylation by PtdIns-4-P 5-kinase and PtdIns 3-kinase. + PtdIns 4-kinase activity is conserved from yeast to higher eukaryotes. Multiple + isoforms of mammalian PtdIns 4-kinase have been purified, and the activities + have been detected in almost all subcellular locations. We previously reported + the cloning and characterization of the first mammalian PtdIns 4-kinase named + PI4K\u03b1 (Wong, K., and Cantley, L. C. (1994) J. Biol. Chem. 269, 28878\u201328884). + Alternatively spliced forms of PI4K\u03b1 have also been identified from several + sources including bovine brain (Gehrmann, T., Vereb, G., Schmidt, M., Klix, + D., Meyer, H. E., Varsanyi, M., and Heilmeyer, L. M., Jr. (1996) Biochim. + Biophys. Acta 1311, 53\u201363). Recently we isolated a distinct human PtdIns + 4-kinase gene, named PI4K\u03b2, that encodes an enzyme that is wortmannin + sensitive (Meyers, R., and Cantley, L. C. (1997) J. Biol. Chem. 272, 4384\u20134390). + Here we report the locations of these enzymes and provide evidence for other + yet unidentified isoforms present in specific organelles. PI4K\u03b1 is mostly + membrane-bound and located at the endoplasmic reticulum; whereas PI4K\u03b2 + is in the cytosol and also present in the Golgi region. Neither of these isoforms + accounts for the major type II PtdIns 4-kinase activity detected in the lysosomes + and plasma membrane fraction.", "venue": "Journal of Biological Chemistry", + "year": 1997, "referenceCount": 31, "citationCount": 183, "influentialCitationCount": + 12, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/272/20/13236.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1997-05-16", "journal": {"volume": "272", "pages": "13236 + - 13241", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "2046941766", "name": "Karen Wong"}, {"authorId": "48408223", "name": "R. + Meyers"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "1af15d0e649fc28c7353c834a3f775962a6d3206", + "externalIds": {"MAG": "2168259122", "DOI": "10.1128/MCB.16.11.6486", "CorpusId": + 21452280, "PubMed": "8887677"}, "corpusId": 21452280, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/1af15d0e649fc28c7353c834a3f775962a6d3206", + "title": "A structural basis for substrate specificities of protein Ser/Thr + kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase + kinase, calmodulin-dependent kinase II, CDK5, and Erk1", "abstract": "We have + developed a method to study the primary sequence specificities of protein + kinases by using an oriented degenerate peptide library. We report here the + substrate specificities of eight protein Ser/Thr kinases. All of the kinases + studied selected distinct optimal substrates. The identified substrate specificities + of these kinases, together with known crystal structures of protein kinase + A, CDK2, Erk2, twitchin, and casein kinase I, provide a structural basis for + the substrate recognition of protein Ser/Thr kinases. In particular, the specific + selection of amino acids at the +1 and -3 positions to the substrate serine/threonine + can be rationalized on the basis of sequences of protein kinases. The identification + of optimal peptide substrates of CDK5, casein kinases I and II, NIMA, calmodulin-dependent + kinases, Erk1, and phosphorylase kinase makes it possible to predict the potential + in vivo targets of these kinases.", "venue": "Molecular and Cellular Biology", + "year": 1996, "referenceCount": 27, "citationCount": 557, "influentialCitationCount": + 15, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1996-11-01", "journal": + {"volume": "16", "pages": "6486 - 6493", "name": "Molecular and Cellular Biology"}, + "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "2070276200", + "name": "K. Lu"}, {"authorId": "152430963", "name": "Y. T. Kwon"}, {"authorId": + "2342352", "name": "L. Tsai"}, {"authorId": "6639228", "name": "O. Filhol"}, + {"authorId": "3289173", "name": "C. Cochet"}, {"authorId": "4426396", "name": + "D. Brickey"}, {"authorId": "6789866", "name": "T. Soderling"}, {"authorId": + "40497410", "name": "C. Bartleson"}, {"authorId": "2006315", "name": "D. Graves"}, + {"authorId": "6941515", "name": "A. Demaggio"}, {"authorId": "4939757", "name": + "M. Hoekstra"}, {"authorId": "4037343", "name": "J. Blenis"}, {"authorId": + "143683912", "name": "T. Hunter"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "2a4f3da9edaf015dc9d607da7e7acd1df904307c", "externalIds": {"MAG": + "2131134035", "DOI": "10.1002/j.1460-2075.1996.tb00965.x", "CorpusId": 25498292, + "PubMed": "8918456"}, "corpusId": 25498292, "publicationVenue": {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", + "name": "EMBO Journal", "type": "journal", "alternate_names": ["The EMBO Journal", + "EMBO J"], "issn": "0261-4189", "url": "http://embojournal.npgjournals.com/", + "alternate_urls": ["http://emboj.embopress.org/"]}, "url": "https://www.semanticscholar.org/paper/2a4f3da9edaf015dc9d607da7e7acd1df904307c", + "title": "Sequence requirements for the recognition of tyrosine\u2010based + endocytic signals by clathrin AP\u20102 complexes.", "abstract": "We recently + determined that fusion proteins containing tyrosine\u2010based endocytic signals + bind to the mu 2 subunit of AP\u20102, the complex that drives clathrin coat + formation and mediates endocytosis from the plasma membrane. Here we analyze + the selectivity of peptide recognition by mu 2 and by AP\u20102 using combinatorial + selection methods and surface plasmon resonance. Both mu 2 and AP\u20102 are + shown to interact with various sequences of the form tyrosine\u2010polar\u2010polar\u2010hydrophobic + (Ypp\u00f8) found on receptors that follow the clathrin pathway. The optimal + sequence for interaction with mu 2 and with AP\u20102 has tyrosine as an anchor + and prefers arginine at position Y + 2 and leucine at position Y + 3. In contrast, + no preferred sequence is detected surrounding the Ypp\u00f8 signal, indicating + that recognition of the Ypp\u00f8 endocytic signal does not require a prefolded + structure. We conclude that sorting into the endocytic pathway is governed + by a surprisingly simple interaction between the mu 2 chain and a tyrosine\u2010containing + tetrapeptide sequence.", "venue": "EMBO Journal", "year": 1996, "referenceCount": + 0, "citationCount": 273, "influentialCitationCount": 7, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc452326?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1996-11-01", "journal": {"volume": + "15", "name": "The EMBO Journal"}, "authors": [{"authorId": "6576021", "name": + "W. Boll"}, {"authorId": "145183789", "name": "H. Ohno"}, {"authorId": "6731027", + "name": "Z. Songyang"}, {"authorId": "2053078190", "name": "I. Rapoport"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5269672", "name": + "J. Bonifacino"}, {"authorId": "4218577", "name": "T. Kirchhausen"}]}, {"paperId": + "32f985d4f7f9c89ebaae84251ecbba97cc65de65", "externalIds": {"MAG": "2048926606", + "DOI": "10.1074/jbc.271.20.11787", "CorpusId": 36378361, "PubMed": "8662772"}, + "corpusId": 36378361, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/32f985d4f7f9c89ebaae84251ecbba97cc65de65", + "title": "Binding Specificity and Mutational Analysis of the Phosphotyrosine + Binding Domain of the Brain-specific Adaptor Protein ShcC (*)", "abstract": + "Shc proteins (hereafter referred to as ShcA) represent major substrates of + tyrosine phosphorylation by a wide variety of growth factors and cytokines. + We have recently described a novel ShcA-like protein, ShcC, which like ShcA + contains an NH-terminal phosphotyrosine binding domain (PTB), a central effector + region (CH1) and a COOH-terminal Src homology 2 domain (SH2). Both the SH2 + and PTB domains of ShcC bind a similar profile of proteins as the comparable + regions of ShcA. In an effort to define the functional differences or similarities + between ShcA and ShcC, we have further characterized the PTB domain of ShcC. + Using a degenerate phosphopeptide library screen, we show that the PTB domain + of ShcC preferentially binds the sequence His-hydrophobic-Asn/hydrophobic-Asn-Pro-Ser/Thr-Tyr(P). + This sequence is similar to the binding site for the ShcA PTB domain, suggesting + that these two proteins may have overlapping specificities. In addition, random + mutagenesis of the ShcC PTB domain has identified several amino acids important + for PTB function (Gly, Glu, Ala, Gly, and Asp). Mutation of these amino acids + dramatically reduces the affinity of the ShcC PTB domain for the activated + epidermal growth factor receptor in vitro.", "venue": "Journal of Biological + Chemistry", "year": 1996, "referenceCount": 29, "citationCount": 20, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925818826217/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1996-05-17", "journal": {"volume": "271", "pages": "11787 - 11791", "name": + "The Journal of Biological Chemistry"}, "authors": [{"authorId": "1403224640", + "name": "J. O\u2019Bryan"}, {"authorId": "50483976", "name": "C. Martin"}, + {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4764611", "name": "C. Der"}]}, {"paperId": "4b203b72d7396db076229654157934d534be1943", + "externalIds": {"MAG": "28313440", "DOI": "10.1007/978-1-4899-1361-6_4", "CorpusId": + 92579248}, "corpusId": 92579248, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/4b203b72d7396db076229654157934d534be1943", + "title": "PI 3-Kinase and Receptor-Linked Signal Transduction", "abstract": + null, "venue": "", "year": 1996, "referenceCount": 194, "citationCount": 10, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Computer Science", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "", "pages": "125-175", + "name": ""}, "authors": [{"authorId": "21162853", "name": "B. Duckworth"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "51e176586c3075290705c0aeb61e756607cccd04", + "externalIds": {"MAG": "175250784", "DOI": "10.1007/978-3-642-61180-3_2", + "CorpusId": 82312158}, "corpusId": 82312158, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/51e176586c3075290705c0aeb61e756607cccd04", + "title": "The Structural Basis for Specificity in Protein-Tyrosine Kinase + Signaling", "abstract": null, "venue": "", "year": 1996, "referenceCount": + 19, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "pages": "5-16", "name": ""}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6731027", "name": "Z. Songyang"}]}, {"paperId": + "5c9060ce2a37eb3dd5d6e15e290e27189bb11908", "externalIds": {"MAG": "2029164510", + "DOI": "10.1016/0167-4889(95)00176-X", "CorpusId": 32513505, "PubMed": "8603102"}, + "corpusId": 32513505, "publicationVenue": {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", + "name": "Biochimica et Biophysica Acta", "type": "journal", "alternate_names": + ["Biochim Biophys Acta"], "issn": "0006-3002", "alternate_issns": ["1878-2434"], + "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/5c9060ce2a37eb3dd5d6e15e290e27189bb11908", + "title": "Association of phosphatidylinositol 3-kinase, via the SH2 domains + of p85, with focal adhesion kinase in polyoma middle t-transformed fibroblasts.", + "abstract": null, "venue": "Biochimica et Biophysica Acta", "year": 1996, + "referenceCount": 50, "citationCount": 40, "influentialCitationCount": 2, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1996-03-27", "journal": {"volume": "1311 1", "pages": "\n 45-52\n ", + "name": "Biochimica et biophysica acta"}, "authors": [{"authorId": "13478754", + "name": "C. Bachelot"}, {"authorId": "4109960", "name": "L. Rameh"}, {"authorId": + "2061061776", "name": "T. Parsons"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "609a94ea2cd6ad7de090ff6c61f87e29b8020e82", "externalIds": {"MAG": + "1977891434", "DOI": "10.1074/jbc.271.27.15934", "CorpusId": 42671115, "PubMed": + "8663233"}, "corpusId": 42671115, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/609a94ea2cd6ad7de090ff6c61f87e29b8020e82", + "title": "Specificity of LIM Domain Interactions with Receptor Tyrosine Kinases*", + "abstract": "LIM domains, Cys-rich motifs containing approximately 50 amino + acids found in a variety of proteins, are proposed to direct protein\u00b7protein + interactions. To identify structural targets recognized by LIM domains, we + have utilized random peptide library selection, the yeast two-hybrid system, + and glutathione S-transferase fusions. Enigma contains three LIM domains within + its carboxyl terminus and LIM3 of Enigma specifically recognizes active but + not mutant endocytic codes of the insulin receptor (InsR) (Wu, R. Y., and + Gill, G. N. (1994)J. Biol. Chem. 269, 25085-25090). Interaction of two random + peptide libraries with glutathione S-transferase-LIM3 of Enigma indicated + specific binding to Gly-Pro-Hyd-Gly-Pro-Hyd-Tyr-Ala corresponding to the major + endocytic code of InsR. Peptide competition demonstrated that both Pro and + Tyr residues were required for specific interaction of InsR with Enigma. In + contrast to LIM3 of Enigma binding to InsR, LIM2 of Enigma associated specifically + with the receptor tyrosine kinase, Ret. Ret was specific for LIM2 of Enigma + and did not bind other LIM domains tested. Mutational analysis indicated that + the residues responsible for binding to Enigma were localized to the carboxyl-terminal + 61 amino acids of Ret. A peptide corresponding to the carboxyl-terminal 20 + amino acids of Ret dissociated Enigma and Ret complexes, while a mutant that + changed Asn-Lys-Leu-Tyr in the peptide to Ala-Lys-Leu-Ala or a peptide corresponding + to exon16 of InsR failed to disrupt the complexes, indicating the Asn-Lys-Leu-Tyr + sequence of Ret is essential to the recognition motif for LIM2 of Enigma. + We conclude that LIM domains of Enigma recognize tyrosine-containing motifs + with specificity residing in both the LIM domains and in the target structures.", + "venue": "Journal of Biological Chemistry", "year": 1996, "referenceCount": + 43, "citationCount": 98, "influentialCitationCount": 5, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/271/27/15934.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1996-07-05", "journal": {"volume": + "271", "pages": "15934 - 15941", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "90528521", "name": "R. Wu"}, {"authorId": "4012671", + "name": "K. Durick"}, {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "1396694186", "name": "S. Taylor"}, + {"authorId": "1977402", "name": "G. Gill"}]}, {"paperId": "660ac58e4ce0fe53df336fa45f6f8c802a339c98", + "externalIds": {"MAG": "2006844704", "DOI": "10.1016/0304-419X(96)00018-2", + "CorpusId": 12934303, "PubMed": "8764841"}, "corpusId": 12934303, "publicationVenue": + {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", "name": "Biochimica et Biophysica + Acta", "type": "journal", "alternate_names": ["Biochim Biophys Acta"], "issn": + "0006-3002", "alternate_issns": ["1878-2434"], "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/660ac58e4ce0fe53df336fa45f6f8c802a339c98", + "title": "Phosphoinositide 3-kinase and the regulation of cell growth.", "abstract": + null, "venue": "Biochimica et Biophysica Acta", "year": 1996, "referenceCount": + 60, "citationCount": 128, "influentialCitationCount": 10, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "JournalArticle"], "publicationDate": "1996-08-08", + "journal": {"volume": "1288 1", "pages": "\n M11-6\n ", "name": + "Biochimica et biophysica acta"}, "authors": [{"authorId": "2972505", "name": + "C. Carpenter"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "6e8f5fcc6b2a51c964d4a3c796953bd86f95fee9", "externalIds": {"MAG": "2029849554", + "DOI": "10.1074/JBC.271.1.563", "CorpusId": 37141087, "PubMed": "8550620"}, + "corpusId": 37141087, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/6e8f5fcc6b2a51c964d4a3c796953bd86f95fee9", + "title": "p120 Is a Cytosolic Adapter Protein That Associates with Phosphoinositide + 3-Kinase in Response to Epidermal Growth Factor in PC12 and Other Cells (*)", + "abstract": "Although epidermal growth factor (EGF) activates phosphoinositide + (PI) 3-kinase activity in a number of types of cells or cell lines, in most + cases that we have investigated the p85 regulatory subunit of PI 3-kinase + does not appear to bind directly to the EGF receptor. Previously we demonstrated + that EGF-dependent activation of PI 3-kinase activity in A431 cells is accompanied + by the binding of p85 to ErbB3, an EGF receptor homologue. However, this mechanism + did not explain the large activation of PI 3-kinase activity that was found + in PC12 and A549 cells, which possess little or no ErbB3. Here we provide + evidence that the p120 proto-oncoprotein is an intracellular adapter protein + that associates with PI 3-kinase and thus is involved in the EGF-dependent + activation of this enzyme in these two cell lines. Using an anti-p120 antibody, + we immunoprecipitated the EGF receptor from PC12 cells and PI 3-kinase activity + from PC12 and A549 cells in an EGF-dependent fashion. Treatment of PC12 cells + with nerve growth factor or insulin stimulated large increases in PI 3-kinase + activity that was immunoprecipitated using anti-Tyr(P) antibody but not using + anti-p120 antibody. In EGF-treated PC12 cells, the tyrosine phosphorylation + of p120 displayed similar kinetics to the activation of PI 3-kinase as measured + by both in vivo lipid production and lipid kinase assays conducted using anti-p120 + and anti-Tyr(P) immunoprecipitates. The use of glutathione S-transferase fusion + proteins of various domains of p85 demonstrated that p120 associated with + both the SH2 and SH3 domains of p85. p120 was also present in A431 cells and + offers an additional pathway by which EGF can activate PI 3-kinase in these + cells.", "venue": "Journal of Biological Chemistry", "year": 1996, "referenceCount": + 25, "citationCount": 152, "influentialCitationCount": 7, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/271/1/563.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1996-01-05", "journal": {"volume": + "271", "pages": "563 - 567", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "9ab201a03716fc9886a650e6c03cf71d6492345f", + "externalIds": {"MAG": "1985782864", "DOI": "10.1074/jbc.271.46.29271", "CorpusId": + 31687634, "PubMed": "8910587"}, "corpusId": 31687634, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/9ab201a03716fc9886a650e6c03cf71d6492345f", + "title": "The Inositol 5\u2032-Phosphatase SHIP Binds to Immunoreceptor Signaling + Motifs and Responds to High Affinity IgE Receptor Aggregation*", "abstract": + "Immunoreceptors such as the high affinity IgE receptor, Fc\u03b5RI, and T-cell + receptor-associated proteins share a common motif, the immunoreceptor tyrosine-based + activation motif (ITAM). We used the yeast tribrid system to identify downstream + effectors of the phosphorylated Fc\u03b5RI ITAM-containing subunits \u03b2 + and \u03b3. One novel cDNA was isolated that encodes a protein that is phosphorylated + on tyrosine, contains a Src-homology 2 (SH2) domain, inositolpolyphosphate + 5-phosphatase activity, three NXXY motifs, several proline-rich regions, and + is called SHIP. Mutation of the conserved tyrosine or leucine residues within + the Fc\u03b5RI \u03b2 or \u03b3 ITAMs eliminates SHIP binding and indicates + that the SHIP-ITAM interaction is specific. SHIP also binds to ITAMs from + the CD3 complex and T cell receptor \u03b6 chain in vitro. SHIP protein possesses + both phosphatidylinositol-3,4,5-trisphosphate 5\u2032-phosphatase and inositol-1,3,4,5-tetrakisphosphate + 5\u2032-phosphatase activity. Phosphorylation of SHIP by a protein-tyrosine + kinase, Lck, results in a reduction in enzyme activity. Fc\u03b5RI activation + induces the association of several tyrosine phosphoproteins with SHIP. SHIP + is constitutively tyrosine-phosphorylated and associated with Shc and Grb2. + These data suggest that SHIP may serve as a multifunctional linker protein + in receptor activation.", "venue": "Journal of Biological Chemistry", "year": + 1996, "referenceCount": 46, "citationCount": 200, "influentialCitationCount": + 11, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925818350622/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1996-11-15", "journal": {"volume": + "271", "pages": "29271 - 29278", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "48234741", "name": "M. Osborne"}, {"authorId": "6208795", + "name": "Georg Zenner"}, {"authorId": "16342565", "name": "M. Lubinus"}, {"authorId": + "2118044546", "name": "Xiaoling Zhang"}, {"authorId": "6731027", "name": "Z. + Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2676378", + "name": "P. Majerus"}, {"authorId": "145340757", "name": "P. Burn"}, {"authorId": + "7659975", "name": "J. Kochan"}]}, {"paperId": "9b67ff313f2759f8cf79a512cf15c3c0dbcde336", + "externalIds": {"MAG": "2132366506", "DOI": "10.1016/S0092-8674(00)81814-0", + "CorpusId": 3010436, "PubMed": "8980225"}, "corpusId": 3010436, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/9b67ff313f2759f8cf79a512cf15c3c0dbcde336", + "title": "Vascular Dysmorphogenesis Caused by an Activating Mutation in the + Receptor Tyrosine Kinase TIE2", "abstract": null, "venue": "Cell", "year": + 1996, "referenceCount": 67, "citationCount": 746, "influentialCitationCount": + 22, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.cell.com/article/S0092867400818140/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1996-12-27", "journal": {"volume": + "87", "pages": "1181-1190", "name": "Cell"}, "authors": [{"authorId": "3640552", + "name": "M. Vikkula"}, {"authorId": "6863639", "name": "L. Boon"}, {"authorId": + "1438822712", "name": "Kermit L.Carraway"}, {"authorId": "48532116", "name": + "J. T. Calvert"}, {"authorId": "48917515", "name": "A. Diamonti"}, {"authorId": + "4268821", "name": "B. Goumnerov"}, {"authorId": "4034486", "name": "K. Pasyk"}, + {"authorId": "6555638", "name": "D. Marchuk"}, {"authorId": "3999657", "name": + "M. Warman"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3892628", "name": "J. Mulliken"}, {"authorId": "1818556", "name": "B. Olsen"}]}, + {"paperId": "9ea425d0943a7cc39526698fdb2795ace1d9863c", "externalIds": {"MAG": + "2000790515", "DOI": "10.1006/GENO.1996.0527", "CorpusId": 84731266}, "corpusId": + 84731266, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/9ea425d0943a7cc39526698fdb2795ace1d9863c", + "title": "Structural Organization and Alternative Splicing of the Murine Phosphoinositide + 3-Kinase p85\u03b1 Gene", "abstract": "Phosphoinositide 3-kinase is a lipid + and protein kinase composed of a 110-kDa catalytic subunit and an 85-kDa (p85) + or 55-kDa (p55) regulatory subunit. In mammals, at least two genes encode + catalytic subunits, and at least three genes encode regulatory subunits. Here + we report the cloning and structural analysis of the mouse p85 alpha gene. + The translated portion of mouse p85 alpha is encoded by 15 exons that span + at least 40 kb. We have cloned an alternatively spliced form of p85 alpha + from both mouse and rat cDNA libraries. This splice variant encodes a unique + 5''-untranslated region, start codon, and 6-amino-acid aminoterminus followed + by the carboxyterminal 418 amino acids of p85 alpha. A corresponding exon + is present within the p85 alpha genomic locus. In vitro transcription and + translation of the splice variant cDNA generate a protein of approximately + 45 kDa that is reactive with an anti-p85 alpha antiserum. Northern blot analysis + of mouse tissues reveals differential expression of full-length and alternatively + spliced p85 alpha, with the splice variant most abundant in the liver.", "venue": + "", "year": 1996, "referenceCount": 0, "citationCount": 105, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Computer Science", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "1996-10-01", + "journal": {"volume": "37", "pages": "113-121", "name": "Genomics"}, "authors": + [{"authorId": "6241317", "name": "D. Fruman"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "2972505", "name": "C. Carpenter"}]}, {"paperId": + "b7b1b863403ea98759a6a5262c3574a8144c49f2", "externalIds": {"CorpusId": 40022962, + "PubMed": "8921377"}, "corpusId": 40022962, "publicationVenue": {"id": "85914651-dd2f-4b80-84eb-9e87943a555b", + "name": "Genomics", "type": "journal", "issn": "0888-7543", "url": "https://www.journals.elsevier.com/genomics", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/08887543", + "http://www.idealibrary.com/links/toc/geno", "http://www.journals.elsevier.com/genomics"]}, + "url": "https://www.semanticscholar.org/paper/b7b1b863403ea98759a6a5262c3574a8144c49f2", + "title": "Structural organization and alternative splicing of the murine phosphoinositide + 3-kinase p85 alpha gene.", "abstract": "Phosphoinositide 3-kinase is a lipid + and protein kinase composed of a 110-kDa catalytic subunit and an 85-kDa (p85) + or 55-kDa (p55) regulatory subunit. In mammals, at least two genes encode + catalytic subunits, and at least three genes encode regulatory subunits. Here + we report the cloning and structural analysis of the mouse p85 alpha gene. + The translated portion of mouse p85 alpha is encoded by 15 exons that span + at least 40 kb. We have cloned an alternatively spliced form of p85 alpha + from both mouse and rat cDNA libraries. This splice variant encodes a unique + 5''-untranslated region, start codon, and 6-amino-acid aminoterminus followed + by the carboxyterminal 418 amino acids of p85 alpha. A corresponding exon + is present within the p85 alpha genomic locus. In vitro transcription and + translation of the splice variant cDNA generate a protein of approximately + 45 kDa that is reactive with an anti-p85 alpha antiserum. Northern blot analysis + of mouse tissues reveals differential expression of full-length and alternatively + spliced p85 alpha, with the splice variant most abundant in the liver.", "venue": + "Genomics", "year": 1996, "referenceCount": 0, "citationCount": 40, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Computer Science", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "37 1", "pages": "\n 113-21\n ", + "name": "Genomics"}, "authors": [{"authorId": "6241317", "name": "D. Fruman"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2972505", "name": + "C. Carpenter"}]}, {"paperId": "c457f5f005f88d0209fd9850e38bc94cbdcd57df", + "externalIds": {"DOI": "10.1016/s0955-0674(96)80060-3", "CorpusId": 42258451, + "PubMed": "8791418"}, "corpusId": 42258451, "publicationVenue": {"id": "bda8ed3e-063e-43a6-ba9e-f4357d8a3e66", + "name": "Current Opinion in Cell Biology", "type": "journal", "alternate_names": + ["Curr Opin Cell Biology"], "issn": "0955-0674", "url": "http://journals.elsevier.com/09550674/current-opinion-in-cell-biology/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/09550674"]}, + "url": "https://www.semanticscholar.org/paper/c457f5f005f88d0209fd9850e38bc94cbdcd57df", + "title": "Phosphoinositide kinases.", "abstract": null, "venue": "Current + Opinion in Cell Biology", "year": 1996, "referenceCount": 0, "citationCount": + 11, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": null, "journal": {"volume": + "8 2", "pages": "\n 153-8\n ", "name": "Current opinion in + cell biology"}, "authors": [{"authorId": "2972505", "name": "C. Carpenter"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ca3d7470be7af31b15c900d32045ab53bae70e75", + "externalIds": {"MAG": "2054805783", "DOI": "10.1074/jbc.271.51.32986", "CorpusId": + 35660758, "PubMed": "8955143"}, "corpusId": 35660758, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/ca3d7470be7af31b15c900d32045ab53bae70e75", + "title": "D3 Phosphoinositides and Outside-in integrin Signaling by Glycoprotein + IIb-IIIa Mediate Platelet Actin Assembly and Filopodial Extension Induced + by Phorbol 12-Myristate 13-Acetate*", "abstract": "Phorbol 12-myristate 13-acetate + (PMA) uncaps a small number of the fast-growing (barbed) ends of actin filaments, + thereby eliciting slow actin assembly and extension of filopodia in human + blood platelets. These reactions, which also occur in response to immunologic + perturbation of the integrin glycoprotein (GP) IIb-IIIa, are sensitive to + the phosphoinositide 3-kinase inhibitor wortmannin. Platelets deficient in + GPIIb-IIIa integrins or with GPIIb-IIIa function inhibited by calcium chelation + or the peptide RGDS have diminished PMA responsiveness. The effects of PMA + contrast with thrombin receptor stimulation by \u22655 \u03bcM thrombin receptor-activating + peptide (TRAP), which causes rapid and massive wortmannin-insensitive actin + assembly and lamellar and filopodial extension. However, we show here that + wortmannin can inhibit filopod formation if the thrombin receptor is ligated + using suboptimal doses (<1 \u03bcM) of TRAP. Phosphatidylinositol 3,4-bisphosphate + inhibits actin filament severing and capping by human gelsolin in vitro. The + findings implicate D3 polyphosphoinositides and integrin signaling in PMA-mediated + platelet stimulation and implicate D3 containing phosphoinositides generated + in response to protein kinase C activation and GPIIb-IIIa signaling as late-acting + intermediates leading to filopodial actin assembly.", "venue": "Journal of + Biological Chemistry", "year": 1996, "referenceCount": 47, "citationCount": + 130, "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/article/S0021925819788085/pdf", "status": null}, + "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1996-12-20", "journal": {"volume": "271", "pages": "32986 + - 32993", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "2999768", "name": "J. Hartwig"}, {"authorId": "2120653511", "name": "Sophia + Kung"}, {"authorId": "46327570", "name": "T. Kovacsovics"}, {"authorId": "2194622", + "name": "P. Janmey"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5661139", "name": "T. Stossel"}, {"authorId": "145751285", "name": "A. Toker"}]}, + {"paperId": "d82b268bfd494a0a391f72e8886250ad95dbb611", "externalIds": {"MAG": + "2054792404", "DOI": "10.1073/PNAS.93.25.14373", "CorpusId": 35192014, "PubMed": + "8962058"}, "corpusId": 35192014, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/d82b268bfd494a0a391f72e8886250ad95dbb611", + "title": "Crystal structure of the breakpoint cluster region-homology domain + from phosphoinositide 3-kinase p85 alpha subunit.", "abstract": "Proteins + such as the product of the break-point cluster region, chimaerin, and the + Src homology 3-binding protein 3BP1, are GTPase activating proteins (GAPs) + for members of the Rho subfamily of small GTP-binding proteins (G proteins + or GTPases). A 200-residue region, named the breakpoint cluster region-homology + (BH) domain, is responsible for the GAP activity. We describe here the crystal + structure of the BH domain from the p85 subunit of phosphatidylinositol 3-kinase + at 2.0 A resolution. The domain is composed of seven helices, having a previously + unobserved arrangement. A core of four helices contains most residues that + are conserved in the BH family. Their packing suggests the location of a G-protein + binding site. This structure of a GAP-like domain for small GTP-binding proteins + provides a framework for analyzing the function of this class of molecules.", + "venue": "Proceedings of the National Academy of Sciences of the United States + of America", "year": 1996, "referenceCount": 35, "citationCount": 112, "influentialCitationCount": + 6, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc26139?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1996-12-10", "journal": {"volume": "93 25", "pages": "\n 14373-8\n ", + "name": "Proceedings of the National Academy of Sciences of the United States + of America"}, "authors": [{"authorId": "4370379", "name": "A. Musacchio"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2150243975", + "name": "S. Harrison"}]}, {"paperId": "e43083320ee529615d58520229c32870a19cac7c", + "externalIds": {"MAG": "2100426048", "DOI": "10.1073/PNAS.93.7.2729", "CorpusId": + 39845223, "PubMed": "8610109"}, "corpusId": 39845223, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/e43083320ee529615d58520229c32870a19cac7c", + "title": "A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding + domains is related to Shc and is specifically expressed in the brain.", "abstract": + "The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct + phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain + and an N-terminal phosphotyrosine-binding (PTB) domain, and is itself phosphorylated + on tyrosine in response to many extracellular signals. Phosphorylation of + human ShcA at Tyr-317 within its central (CH1) region induces binding to the + Grb2 SH2 domain and is thereby implicated in activation of the Ras pathway. + Two shc-related genes (shcB and shcC) have been identified in the mouse. shcB + is closely related to human SCK, while shcC has not yet been found in other + organisms. The ShcC protein is predicted to have a C-terminal SH2 domain, + a CH1 region with a putative Grb2-binding site, and an N-terminal PTB domain. + The ShcC and ShcB SH2 domains bind phosphotyrosine-containing peptides and + receptors with a specificity related to, but distinct from, that of the ShcA + SH2 domain. The ShcC PTB domain specifically associates in vitro with the + autophosphorylated receptors for nerve growth factor and epidermal growth + factor. These results indicate that ShcC has functional SH2 and PTB; domains. + In contrast to shcA, which is widely expressed, shcC RNA and proteins are + predominantly expressed in the adult brain. These results suggest that ShcC + may mediate signaling from tyrosine kinases in the nervous system, such as + receptors for neurotrophins.", "venue": "Proceedings of the National Academy + of Sciences of the United States of America", "year": 1996, "referenceCount": + 32, "citationCount": 106, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc39699?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1996-04-02", "journal": {"volume": "93 7", "pages": + "\n 2729-34\n ", "name": "Proceedings of the National Academy + of Sciences of the United States of America"}, "authors": [{"authorId": "1403224640", + "name": "J. O\u2019Bryan"}, {"authorId": "6731027", "name": "Z. Songyang"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4764611", "name": + "C. Der"}, {"authorId": "50999462", "name": "T. Pawson"}]}, {"paperId": "edefa2933abf64298f4f8e67389f3ad5dd9cae5b", + "externalIds": {"MAG": "2110143939", "DOI": "10.1128/MCB.16.10.5905", "CorpusId": + 19784641, "PubMed": "8816504"}, "corpusId": 19784641, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/edefa2933abf64298f4f8e67389f3ad5dd9cae5b", + "title": "Platelet-derived growth factor-dependent activation of phosphatidylinositol + 3-kinase is regulated by receptor binding of SH2-domain-containing proteins + which influence Ras activity", "abstract": "Upon binding of platelet-derived + growth factor (PDGF), the PDGF beta receptor (PDGFR) undergoes autophosphorylation + on distinct tyrosine residues and binds several SH2-domain-containing signal + relay enzymes, including phosphatidylinositol 3-kinase (PI3K), phospholipase + C gamma (PLC gamma), the GTPase-activating protein of Ras (RasGAP), and the + tyrosine phosphatase SHP-2. In this study, we have investigated whether PDGF-dependent + PI3K activation is affected by the other proteins that associate with the + PDGFR. We constructed and characterized a series of PDGFR mutants which contain + binding sites for PI3K as well as one additional protein, either RasGAP, SHP-2, + or PLC gamma. While all of the receptors had wild-type levels of PDGF-stimulated + tyrosine kinase activity and associated with comparable amounts of PI3K activity, + their abilities to trigger accumulation of PI3K products in vivo differed + dramatically. The wild-type receptor, as well as receptors that recruited + PI3K or PI3K and SHP-2, were all capable of fully activating PI3K. In contrast, + receptors that associated with PI3K and RasGAP or PI3K and PLC gamma displayed + a greatly reduced ability to stimulate production of PI3K products. When this + series of receptors was tested for their ability to activate Ras, we observed + a strong positive correlation between Ras activation and PI3K activation. + Further investigation of the relationship between Ras and PI3K indicated that + Ras was upstream of PI3K. Thus, activation of PI3K requires not only binding + of PI3K to the tyrosine-phosphorylated PDGFR but accumulation of GTP-bound + Ras as well. Furthermore, PLC gamma and RasGAP negatively modulate PDGF-dependent + PI3K activation. Finally, PDGF-stimulated signal relay can be regulated by + altering the ratio of SH2-domain-containing enzymes that are recruited to + the PDGFR.", "venue": "Molecular and Cellular Biology", "year": 1996, "referenceCount": + 47, "citationCount": 143, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc231592?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1996-10-01", "journal": {"volume": "16", "pages": "5905 + - 5914", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "4606242", "name": "R. Klinghoffer"}, {"authorId": "21162853", "name": "B. + Duckworth"}, {"authorId": "49879061", "name": "M. Valius"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "49161111", "name": "A. Kazlauskas"}]}, + {"paperId": "fc8d01ca34e728d8143b26fbd29682277db3d14d", "externalIds": {"MAG": + "2072499270", "DOI": "10.1074/jbc.271.40.24880", "CorpusId": 24714762, "PubMed": + "8798764"}, "corpusId": 24714762, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/fc8d01ca34e728d8143b26fbd29682277db3d14d", + "title": "Regulation of the Lck SH2 Domain by Tyrosine Phosphorylation*", + "abstract": "Src homology 2 (SH2) domains bind to phosphotyrosine (Tyr(P)) + residues in specific sequence contexts in other proteins and thereby mediate + tyrosine phosphorylationdependent protein-protein interactions. The SH2 domain + of the Src family kinase Lck is phosphorylated at tyrosine 192 in T cells + upon T cell antigen receptor triggering. We have studied the consequences + of this phosphorylation on the properties of the SH2 domain and on the function + of Lck in T cell activation. We report that phosphorylation at Tyr192 reduced + the capacity of the isolated SH2 domain to bind a high affinity peptide ligand + and Tyr(P)-containing cellular proteins. This effect was mimicked by mutation + of Tyr192 to an acidic residue. In intact T cells, where Lck participates + in T cell antigen receptor signal transduction in an SH2 domain-dependent + manner, phosphorylation of Tyr192 correlated with reduced downstream signaling. + Our results indicate that tyrosine phosphorylation of the SH2 domain of Lck + terminates its high affinity binding to ligands, thereby negatively regulating + its participation in T cell antigen receptor signaling. This represents a + novel mechanism for the regulation of the function of SH2 domains.", "venue": + "Journal of Biological Chemistry", "year": 1996, "referenceCount": 33, "citationCount": + 80, "influentialCitationCount": 4, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/article/S0021925818400889/pdf", "status": null}, + "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1996-10-04", "journal": {"volume": "271", "pages": "24880 - 24884", "name": + "The Journal of Biological Chemistry"}, "authors": [{"authorId": "47751552", + "name": "C. Couture"}, {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": + "5844467", "name": "T. Jascur"}, {"authorId": "10028783", "name": "Scott M. + Williams"}, {"authorId": "38501602", "name": "P. Tailor"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "5389022", "name": "T. Mustelin"}]}, {"paperId": + "07bd79d241abd67df644cdb500f07b4c88ecfbb0", "externalIds": {"MAG": "1982304503", + "DOI": "10.1016/0092-8674(95)90525-1", "CorpusId": 15869636, "PubMed": "7774006"}, + "corpusId": 15869636, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/07bd79d241abd67df644cdb500f07b4c88ecfbb0", + "title": "Signal transduction and membrane traffic: The PITP/phosphoinositide + connection", "abstract": null, "venue": "Cell", "year": 1995, "referenceCount": + 30, "citationCount": 259, "influentialCitationCount": 6, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "1995-06-02", "journal": + {"volume": "81", "pages": "659-662", "name": "Cell"}, "authors": [{"authorId": + "6319769", "name": "M. Liscovitch"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "145d73a65f6f7c6cd162c8fd8cd2972c85f9841f", "externalIds": {"MAG": + "1966748170", "DOI": "10.1016/0167-4838(95)00016-N", "CorpusId": 8987446, + "PubMed": "7748894"}, "corpusId": 8987446, "publicationVenue": {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", + "name": "Biochimica et Biophysica Acta", "type": "journal", "alternate_names": + ["Biochim Biophys Acta"], "issn": "0006-3002", "alternate_issns": ["1878-2434"], + "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/145d73a65f6f7c6cd162c8fd8cd2972c85f9841f", + "title": "Type 2 phosphatidylinositol 4-kinase is recruited to CD4 in response + to CD4 cross-linking.", "abstract": null, "venue": "Biochimica et Biophysica + Acta", "year": 1995, "referenceCount": 52, "citationCount": 13, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1995-04-27", "journal": {"volume": "1248 2", "pages": "\n 129-34\n ", + "name": "Biochimica et biophysica acta"}, "authors": [{"authorId": "1960212", + "name": "P. Pertile"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "1987fb488beb02b4b52639c7013f4768e27d45b4", "externalIds": {"MAG": "2053139373", + "DOI": "10.1021/JM00021A017", "CorpusId": 40161417, "PubMed": "7473555"}, + "corpusId": 40161417, "publicationVenue": {"id": "4cce60a8-2106-4240-bece-fb6488df6bd1", + "name": "Journal of Medicinal Chemistry", "type": "journal", "alternate_names": + ["J Med Chem"], "issn": "0022-2623", "url": "https://pubs.acs.org/journal/jmcmar", + "alternate_urls": ["http://pubs.acs.org/journal/jmcmar", "http://pubs.acs.org/journals/jmcmar/index.html"]}, + "url": "https://www.semanticscholar.org/paper/1987fb488beb02b4b52639c7013f4768e27d45b4", + "title": "Identification of efficient pentapeptide substrates for the tyrosine + kinase pp60c-src.", "abstract": "The development of inhibitors of protein + tyrosine kinases (PTKs) is a promising approach to obtaining new therapeutic + agents for a variety of diseases, particularly cancer. However, the discovery + of peptide-based inhibitors has been hindered by the lack of small peptide + substrate sequences (i.e. five residues or less) with which a variety of inhibitor + designs could be readily evaluated by replacing the Tyr with natural and unnatural + amino acids. These prototypical small peptide inhibitors could then form the + basis for designing analogous conformationally constrained, peptide-mimetic + or non-peptide inhibitors with improved therapeutic potential. In this study + we have identified the best known small peptide substrate for the PTK pp60c-src, + which is the parent of the src family of nonreceptor PTKs. This pentapeptide + substrate, Ac-Ile-Tyr-Gly-Glu-Phe-NH2, has a Km of 368 microM and Vmax of + 1.02 mumol/min/mg when tested utilizing the assay methodology of Budde et + al. (Anal. Biochem. 1992, 200, 347-351) after a series of modifications were + made to more closely simulate the conditions inside a typical mammalian cell. + This substrate was designed from information obtained by Songyang et al. (Nature + 1995, 373, 536-539) with a 2.5 billion member combinatorial library of peptide + substrates for pp60c-src. A second pentapeptide substrate, Ac-Glu-Asp-Ala-Ile-Tyr-NH2, + with a weaker binding affinity (Km = 880 microM) but improved Vmax (1.86 mumol/min/mg), + was also identified. This peptide was designed from the pp60c-src autophosphorylation + sequence and information obtained by Songyang et al. (Ibid.) and Till et al. + (J. Biol. Chem. 1994, 269, 7423-7428) with combinatorial libraries of peptide + substrates. These new substrates provide sufficient binding affinities and + rates of phosphorylation to be utilized for evaluating the relative effectiveness + of various reversible and mechanism-based irreversible inhibitor designs for + pp60c-src while appended to easily prepared small peptides.", "venue": "Journal + of Medicinal Chemistry", "year": 1995, "referenceCount": 0, "citationCount": + 21, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], + "publicationDate": "1995-10-13", "journal": {"volume": "38 21", "pages": "\n 4276-83\n ", + "name": "Journal of medicinal chemistry"}, "authors": [{"authorId": "152126173", + "name": "S. Nair"}, {"authorId": "2107617132", "name": "M. Kim"}, {"authorId": + "40408634", "name": "S. D. Warren"}, {"authorId": "32145924", "name": "S. + Choi"}, {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "4549140", "name": "D. Hangauer"}]}, {"paperId": + "28b551e0356f678a41dc3d00b14910e262c43424", "externalIds": {"MAG": "2100869656", + "DOI": "10.1016/0092-8674(95)90351-8", "CorpusId": 16866005, "PubMed": "7889566"}, + "corpusId": 16866005, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/28b551e0356f678a41dc3d00b14910e262c43424", + "title": "Specific recruitment of SH-PTP1 to the erythropoietin receptor causes + inactivation of JAK2 and termination of proliferative signals", "abstract": + null, "venue": "Cell", "year": 1995, "referenceCount": 50, "citationCount": + 978, "influentialCitationCount": 30, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1995-03-10", "journal": {"volume": "80", "pages": "729-738", "name": "Cell"}, + "authors": [{"authorId": "1906951", "name": "U. Klingm\u00fcller"}, {"authorId": + "40622792", "name": "U. Lorenz"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2291271", "name": "B. Neel"}, {"authorId": "7757698", "name": + "H. Lodish"}]}, {"paperId": "2a77db9d8590c0a83b3f0bcd1c05fbcc4aa26936", "externalIds": + {"MAG": "2115666887", "CorpusId": 21760382, "PubMed": "7620084"}, "corpusId": + 21760382, "publicationVenue": {"id": "f034b560-0c02-434d-93bc-8cd645d76640", + "name": "Journal of the American Society of Nephrology", "type": "journal", + "alternate_names": ["J Am Soc Nephrol", "Journal of The American Society of + Nephrology"], "issn": "1046-6673", "url": "https://jasn.asnjournals.org/", + "alternate_urls": ["http://www.jasn.org/"]}, "url": "https://www.semanticscholar.org/paper/2a77db9d8590c0a83b3f0bcd1c05fbcc4aa26936", + "title": "Signal transduction by the hepatocyte growth factor receptor, c-met. + Activation of the phosphatidylinositol 3-kinase.", "abstract": "Signal transduction + by tyrosine kinase growth factor receptors involves the activation of multiple + intracellular signaling pathways. In many cases, this occurs via direct binding + of a downstream signaling protein to the phosphorylated receptor via src-homology + 2 domains on the signaling protein. In this review of the hepatocyte growth + factor receptor c-met, the ability of the amino acid sequence of the receptor + to dictate which signaling proteins are activated is described, with particular + emphasis on association with the phosphatidylinositol 3-kinase. Recent developments + that provide new understanding of the mechanisms of downstream signal transduction + by the phosphatidylinositol 3-kinase are discussed, including how these might + be involved in the mitogenic, motogenic, and tubulogenic effects of hepatocyte + growth factor on renal epithelial cells.", "venue": "Journal of the American + Society of Nephrology", "year": 1995, "referenceCount": 93, "citationCount": + 39, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["Review", "Editorial"], "publicationDate": "1995-05-01", + "journal": {"volume": "5 11", "pages": "\n 1872-81\n ", "name": + "Journal of the American Society of Nephrology : JASN"}, "authors": [{"authorId": + "5601835", "name": "L. Cantley"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "2ca38cf48247d33e3f4367bbf687fc8cfd2d6efd", "externalIds": {"MAG": + "2026907934", "DOI": "10.1038/373536A0", "CorpusId": 1105841, "PubMed": "7845468"}, + "corpusId": 1105841, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/2ca38cf48247d33e3f4367bbf687fc8cfd2d6efd", + "title": "Catalytic specificity of protein-tyrosine kinases is critical for + selective signalling", "abstract": null, "venue": "Nature", "year": 1995, + "referenceCount": 23, "citationCount": 914, "influentialCitationCount": 33, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1995-02-09", "journal": {"volume": "373", "pages": "536-539", "name": "Nature"}, + "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "145331905", + "name": "K. Carraway"}, {"authorId": "2026802", "name": "M. Eck"}, {"authorId": + "2150243975", "name": "S. Harrison"}, {"authorId": "48725230", "name": "R. + Feldman"}, {"authorId": "143902042", "name": "M. Mohammadi"}, {"authorId": + "4607078", "name": "J. Schlessinger"}, {"authorId": "34863469", "name": "S. + Hubbard"}, {"authorId": "1949522380", "name": "Darrin P. Smith"}, {"authorId": + "144966010", "name": "C. Eng"}, {"authorId": "50398854", "name": "M. J. Lorenzo"}, + {"authorId": "153509268", "name": "B. Ponder"}, {"authorId": "32634768", "name": + "B. Mayer"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "2d251c6d67c3ec75f99023c8bd202bc202483202", "externalIds": {"MAG": "62744173", + "CorpusId": 33790614, "PubMed": "7537362"}, "corpusId": 33790614, "publicationVenue": + {"id": "55bed249-d30f-456b-9d2c-a51dc149cb7a", "name": "Oncogene", "type": + "journal", "issn": "0950-9232", "url": "http://www.nature.com/onc/", "alternate_urls": + ["http://www.nature.com/onc", "http://www.naturesj.com/onc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/2d251c6d67c3ec75f99023c8bd202bc202483202", + "title": "Molecular interactions of the Src homology 2 domain protein Shb + with phosphotyrosine residues, tyrosine kinase receptors and Src homology + 3 domain proteins.", "abstract": "The molecular interactions of the Src homology + 2 (SH2) domain and the N-terminal proline-rich sequence motifs (pro-1 to pro-5) + of the SH2 protein Shb with other components were presently characterised. + Using a degenerate phosphopeptide library the preferred binding site for the + Shb SH2 domain was determined to pTyr-Thr/Val/Ile-X-Leu at positions +1 to + +3 relative the phosphotyrosine residue. Experiments with competing peptides + and platelet-derived growth factor (PDGF) beta-receptor mutants with Y to + F substitutions in autophosphorylation sites revealed multiple binding sites + for the Shb SH2 domain in the receptor. The Shb SH2 domain also binds to in + vitro phosphorylated fibroblast growth factor receptor-1 (FGFR-1) mainly through + position Y776. The receptor experiments suggest that other residues besides + the +1 to +3 positions may also be of significance for Shb binding. The pro-4/pro-5 + motif of Shb binds in vitro particularly well to the Src, p85 alpha PI3-kinase + and Eps8 SH3 domains expressed as GST fusion proteins. However, the GST-SH3 + domain fusion proteins tested bind in vitro to peptides corresponding to the + pro-1 to pro-5 motifs of Shb with low affinity and selectivity, suggesting + that sequences outside the core proline motif may also be important for Shb-SH3 + domain interactions. In vivo association between Shb-SH3 domain proteins v-Src + and Eps8 was detected by coimmunoprecipitation. PDGF treatment did not affect + the association between Eps8 and Shb. The data suggest that Shb is an adaptor + protein linking SH3 domain proteins to tyrosine kinases or other tyrosine + phosphorylated proteins.", "venue": "Oncogene", "year": 1995, "referenceCount": + 0, "citationCount": 71, "influentialCitationCount": 8, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1995-04-20", "journal": {"volume": "10 8", "pages": "\n 1475-83\n ", + "name": "Oncogene"}, "authors": [{"authorId": "145168992", "name": "T. Karlsson"}, + {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "5057913", "name": + "E. Landgren"}, {"authorId": "117249643", "name": "C. Lavergne"}, {"authorId": + "6724547", "name": "P. P. Di Fiore"}, {"authorId": "4175143", "name": "M. + Anafi"}, {"authorId": "50999462", "name": "T. Pawson"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "1398055038", "name": "L. Claesson-Welsh"}, + {"authorId": "145515062", "name": "M. Welsh"}]}, {"paperId": "305930c1039f12f1fae2ba1381b2e16abc9ea576", + "externalIds": {"MAG": "2001138501", "DOI": "10.1074/JBC.270.49.29525", "CorpusId": + 44991100, "PubMed": "7493994"}, "corpusId": 44991100, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/305930c1039f12f1fae2ba1381b2e16abc9ea576", + "title": "Phosphorylation of the Platelet p47 Phosphoprotein Is Mediated by + the Lipid Products of Phosphoinositide 3-Kinase (*)", "abstract": "Platelet + stimulation by thrombin or the thrombin receptor activating peptide (TRAP) + results in the activation of phosphoinositide 3-kinase and the production + of the novel polyphosphoinositides phosphatidylinositol 3,4-bisphosphate (PtdIns-3,4-P2) + and phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P3). We have shown + previously that these lipids activate calcium-independent protein kinase C + (PKC) isoforms in vitro (Toker, A., Meyer, M., Reddy, K. K., Falck, J. R., + Aneja, R., Aneja, S., Parra, A., Burns, D. J., Ballas, L. M. and Cantley, + L. C.(1994) J. Biol. Chem. 269, 32358-32367). Activation of platelet PKC in + response to TRAP is detected by the phosphorylation of the major PKC substrate + in platelets, the p47 phosphoprotein, also known as pleckstrin. Here we provide + evidence for two phases of pleckstrin phosphorylation in response to TRAP. + A rapid phase of pleckstrin phosphorylation (<1 min) precedes the peak of + PtdIns-3,4-P2 production and is unaffected by concentrations of wortmannin + (10-100 nM) that block production of this lipid. However prolonged phosphorylation + of pleckstrin (>2 min) is inhibited by wortmannin concentrations that block + PtdIns-3,4-P2 production. Phorbol ester-mediated pleckstrin phosphorylation + was not affected by wortmannin and wortmannin had no effect on purified platelet + PKC activity. Phosphorylation of pleckstrin could be induced using permeabilized + platelets supplied with exogenous -P[ATP] and synthetic dipalmitoyl PtdIns-3,4,5-P3 + and dipalmitoyl PtdIns-3,4-P2 micelles, but not with dipalmitoyl phosphatidylinositol + 3-phosphate or phosphatidylinositol 4,5-bisphosphate. These results suggest + two modes of stimulating pleckstrin phosphorylation: a rapid activation of + PKC (via diacylglycerol and calcium) followed by a slower activation of calcium-independent + PKCs via PtdIns-3,4-P2.", "venue": "Journal of Biological Chemistry", "year": + 1995, "referenceCount": 47, "citationCount": 70, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/content/270/49/29525.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1995-12-08", "journal": {"volume": + "270", "pages": "29525 - 29531", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "145751285", "name": "A. Toker"}, {"authorId": "2122133958", + "name": "Christilla Bachelot"}, {"authorId": "2145623779", "name": "Ching-shih + Chen"}, {"authorId": "49877841", "name": "J. Falck"}, {"authorId": "2999768", + "name": "J. Hartwig"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "46327570", "name": "T. Kovacsovics"}]}, {"paperId": "39a24b12ef8f302e0a093dbee2a743e709fef453", + "externalIds": {"MAG": "1493428086", "DOI": "10.1016/0076-6879(95)54037-7", + "CorpusId": 33849856, "PubMed": "8531712"}, "corpusId": 33849856, "publicationVenue": + {"id": "1e7039c8-e30c-4af0-b7d3-f5e05dff5d21", "name": "Methods in Enzymology", + "type": "journal", "alternate_names": ["Method Enzymol"], "issn": "0076-6879", + "alternate_issns": ["1557-7988"], "url": "https://www.elsevier.com/books/book-series/methods-in-enzymology", + "alternate_urls": ["http://www.sciencedirect.com/science/bookseries/00766879"]}, + "url": "https://www.semanticscholar.org/paper/39a24b12ef8f302e0a093dbee2a743e709fef453", + "title": "SH2 domain specificity determination using oriented phosphopeptide + library.", "abstract": null, "venue": "Methods in Enzymology", "year": 1995, + "referenceCount": 18, "citationCount": 38, "influentialCitationCount": 0, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": null, "journal": {"volume": + "254", "pages": "\n 523-35\n ", "name": "Methods in enzymology"}, + "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "3d8292916e5f3c40c09231441c1187995e6fad23", + "externalIds": {"MAG": "1965703662", "DOI": "10.1074/jbc.270.43.25985", "CorpusId": + 83961524}, "corpusId": 83961524, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/3d8292916e5f3c40c09231441c1187995e6fad23", + "title": "Phosphoinositide 3-Kinase Binds Constitutively to \u03b1/\u03b2-Tubulin + and Binds to \u03b3-Tubulin in Response to Insulin (*)", "abstract": "Recently + we reported the localization of phosphoinositide 3-kinase (PI 3-kinase) by + immunofluorescence to microtubule bundles and the centrosome (Kapeller, R., + Chakrabarti, R., Cantley, L., Fay, F., and Corvera, S.(1993) Mol. Cell. Biol. + 13, 6052-6063). [Abstract] In complementary experiments we used the recombinant + p85 subunit of PI 3-kinase to identify proteins that associate with phosphoinositide + 3-kinase and found that phosphoinositide 3-kinase associates with \u03b1/\u03b2-tubulin. + The association occurs in vivo but was not significantly affected by growth + factor stimulation. We localized the region of p85 that interacts with \u03b1/\u03b2-tubulin + to the inter-SH2 domain. These results support the immunofluorescence data + and show that p85 directly associates with \u03b1/\u03b2-tubulin. We then + determined whether phosphoinositide 3-kinase associates with \u03b1/\u03b2-tubulin. + We found a dramatic growth factor-dependent association of phosphoinositide + 3-kinase with \u03b1/\u03b2-tubulin. Phosphoinositide 3-kinase associates + with \u03b1/\u03b2-tubulin in response to insulin and, to a lesser extent, + in response to platelet-derived growth factor. Neither epidermal growth factor + nor nerve growth factor treatment of cells results in association of phosphoinositide + 3-kinase and \u03b1/\u03b2-tubulin. Phosphoinositide 3-kinase is also immunoprecipitated + with antibodies to pericentrin in response to insulin, indicating that phosphoinositide + 3-kinase is recruited to the centrosome. Neither phosphoinositide 3-kinase + activity, nor intact microtubules are necessary for the association. Treatment + of cells with 0.5 M NaCl dissociates \u03b1/\u03b2-tubulin from the centrosome + and disrupts the association of phosphoinositide 3-kinase with pericentrin, + but not \u03b1/\u03b2-tubulin. Recombinant p85 binds to \u03b1/\u03b2-tubulin + from both insulin stimulated and quiescent cells. These results suggest that + the association of phosphoinositide 3-kinase with \u03b1/\u03b2-tubulin is + direct. These data suggest that phosphoinositide 3-kinase may be involved + in regulating microtubule responses to insulin and platelet-derived growth + factor.", "venue": "Journal of Biological Chemistry", "year": 1995, "referenceCount": + 1, "citationCount": 101, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.jbc.org/content/270/43/25985.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": "1995-10-27", "journal": {"volume": "270", "pages": + "25985 - 25991", "name": "The Journal of Biological Chemistry"}, "authors": + [{"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": "145751285", + "name": "A. Toker"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "2972505", "name": "C. Carpenter"}]}, {"paperId": "7ac3a5a9c57138ead45fd881561a80327fef99cd", + "externalIds": {"MAG": "1983672881", "DOI": "10.1074/jbc.270.44.26029", "CorpusId": + 31746462, "PubMed": "7592796"}, "corpusId": 31746462, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/7ac3a5a9c57138ead45fd881561a80327fef99cd", + "title": "A Single Point Mutation Switches the Specificity of Group III Src + Homology (SH) 2 Domains to That of Group I SH2 Domains (*)", "abstract": "Src + homology 2 (SH2) domains recognize phosphotyrosine-containing sequences, and + thereby mediate the association of specific signaling proteins in response + to tyrosine phosphorylation (Pawson, T., and Schlessinger, J.(1993) Curr. + Biol. 3, 434-442). We have shown that specific binding of SH2 domains to tyrosine-phosphorylated + sites is determined by sequences adjacent to the phosphotyrosine. Based on + the phosphopeptide specificity and crystal structures, SH2 domains were classified + into four different groups (Songyang, Z., Shoelson, S. E., Chaudhuri, M., + Gish, G., Pawson, T., Haser, W. G., King, F., Roberts, T., Ratnofsky, S., + Lechleider, R. J., Neel, B. G., R. B. B., Fajardo, J. E., Chou, M. M., Hanafusa, + H., Schaffhausen, B., and Cantley, L. C.(1993) Cell 72, 767-778). The [Medline] + \u03b2D5 residues of SH2 domains were predicted to be critical in distinguishing + these groups (Songyang, Z., Shoelson, S. E., Chaudhuri, M., Gish, G., Pawson, + T., Haser, W. G., King, F., Roberts, T., Ratnofsky, S., Lechleider, R. J., + Neel, B. G., R. B. B., Fajardo, J. E., Chou, M. M., Hanafusa, H., Schaffhausen, + B., and Cantley, L. C.(1993) Cell 72, 767-778; Eck, M. J., Shoelson, S. E., + and Harrison, S. C.(1993) Nature 362, 87-91). We report here that replacing + the aliphatic residues at the \u03b2D5 positions of two Group III SH2 domains + (phosphoinositide 3-kinase N-terminal SH2 domain and phospholipase C- C-terminal + SH2 domain) with Tyr (as found in Group I SH2 domains) results in a switch + in phosphopeptide selectivity, consistent with the specificities of Group + I SH2 domains. These results establish the importance of the \u03b2D5 residue + in determining specificities of SH2 domains.", "venue": "Journal of Biological + Chemistry", "year": 1995, "referenceCount": 14, "citationCount": 84, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925818924348/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "1995-11-03", "journal": {"volume": + "270", "pages": "26029 - 26032", "name": "The Journal of Biological Chemistry"}, + "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "37993016", + "name": "G. Gish"}, {"authorId": "4867984", "name": "G. Mbamalu"}, {"authorId": + "50999462", "name": "T. Pawson"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "8f1fcb734abe42d2a2f2bc839ce7d547eba768bc", "externalIds": {"MAG": + "2020455451", "DOI": "10.1016/S0968-0004(00)89103-3", "CorpusId": 38569154, + "PubMed": "8578591"}, "corpusId": 38569154, "publicationVenue": {"id": "bb8a9b7a-e5e7-4572-b03d-52d99bb0a3b7", + "name": "TIBS -Trends in Biochemical Sciences. Regular ed", "type": "journal", + "alternate_names": ["TIB trends Biochem Sci Regul ed", "Trends Biochem Sci", + "Trends in Biochemical Sciences"], "issn": "0968-0004", "url": "http://www.sciencedirect.com/science/journal/09680004"}, + "url": "https://www.semanticscholar.org/paper/8f1fcb734abe42d2a2f2bc839ce7d547eba768bc", + "title": "Recognition and specificity in protein tyrosine kinase-mediated + signalling.", "abstract": null, "venue": "TIBS -Trends in Biochemical Sciences. + Regular ed", "year": 1995, "referenceCount": 40, "citationCount": 373, "influentialCitationCount": + 14, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "1995-11-01", "journal": + {"volume": "20 11", "pages": "\n 470-5\n ", "name": "Trends + in biochemical sciences"}, "authors": [{"authorId": "6731027", "name": "Z. + Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "9a9f41b1733ea8cebdf98d76e56fed61b8223d1b", + "externalIds": {"MAG": "2060538012", "DOI": "10.1074/JBC.270.30.17656", "CorpusId": + 25210483, "PubMed": "7629060"}, "corpusId": 25210483, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/9a9f41b1733ea8cebdf98d76e56fed61b8223d1b", + "title": "Rho Family GTPases Bind to Phosphoinositide Kinases (*)", "abstract": + "Rho family GTPases appear to play an important role in the regulation of + the actin cytoskeleton, but the mechanism of regulation is unknown. Since + phosphoinositide 3-kinase and phosphatidylinositol 4,5-bisphosphate have also + been implicated in actin reorganization, we investigated the possibility that + Rho family members interact with phosphoinositide kinases. We found that both + GTP- and GDP-bound Rac1 associate with phosphatidylinositol-4-phosphate 5-kinase + in vitro and in vivo. Phosphoinositide 3-kinase also bound to Rac1 and Cdc42Hs, + and these interactions were GTP-dependent. Stimulation of Swiss 3T3 cells + with platelet-derived growth factor induced the association of PI 3-kinase + with Rac in immunoprecipitates. PI 3-kinase activity was also detected in + Cdc42 immunoprecipitates from COS7 cells. These results suggest that phosphoinositide + kinases are involved in Rho family signal transduction pathways and raise + the possibility that the effects of Rho family members on the actin cytoskeleton + are mediated in part by phosphoinositide kinases.", "venue": "Journal of Biological + Chemistry", "year": 1995, "referenceCount": 25, "citationCount": 494, "influentialCitationCount": + 22, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925817479919/pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1995-07-28", "journal": + {"volume": "270", "pages": "17656 - 17659", "name": "The Journal of Biological + Chemistry"}, "authors": [{"authorId": "4661935", "name": "K. Tolias"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2972505", "name": "C. Carpenter"}]}, + {"paperId": "aff5fb19faec26ae778184ee6cd42b9f44839183", "externalIds": {"MAG": + "2075339282", "DOI": "10.1016/0092-8674(95)90195-7", "CorpusId": 2380964, + "PubMed": "8521499"}, "corpusId": 2380964, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/aff5fb19faec26ae778184ee6cd42b9f44839183", + "title": "Phosphatidylinositol (3,4,5)P3 interacts with SH2 domains and modulates + PI 3-kinase association with tyrosine-phosphorylated proteins", "abstract": + null, "venue": "Cell", "year": 1995, "referenceCount": 90, "citationCount": + 305, "influentialCitationCount": 7, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1995-12-01", "journal": + {"volume": "83", "pages": "821-830", "name": "Cell"}, "authors": [{"authorId": + "4109960", "name": "L. Rameh"}, {"authorId": "2145623779", "name": "Ching-shih + Chen"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "c9304f5eebf62399a137f0ea9ff2e1954cddb0ab", + "externalIds": {"MAG": "2040716393", "DOI": "10.1016/1043-6618(95)86360-5", + "CorpusId": 84416505}, "corpusId": 84416505, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/c9304f5eebf62399a137f0ea9ff2e1954cddb0ab", + "title": "Lessons in signal transduction from a DNA tumor virus", "abstract": + null, "venue": "", "year": 1995, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Engineering", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": null, "authors": + [{"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": "8945145", + "name": "M. Yoakim"}, {"authorId": "39702934", "name": "K. P. Mullane"}, {"authorId": + "1438568861", "name": "O. Gj\u00f8rup"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "6665338", "name": "T. Roberts"}, {"authorId": "143744228", + "name": "K. S. Campbell"}, {"authorId": "144344948", "name": "W. Su"}, {"authorId": + "5515098", "name": "D. Pallas"}]}, {"paperId": "d6c86ce9bcd9651dc16a0821b687ebdfce847f6e", + "externalIds": {"MAG": "2917280912", "CorpusId": 86788444}, "corpusId": 86788444, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d6c86ce9bcd9651dc16a0821b687ebdfce847f6e", + "title": "The lipid products of phosphatidylinositol 3-kinase mediate chemotaxis + via protein kinase C", "abstract": null, "venue": "", "year": 1995, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "1995-06-23", "journal": {"volume": + "6", "pages": "789", "name": "Journal of The American Society of Nephrology"}, + "authors": [{"authorId": "144476444", "name": "M. Derman"}, {"authorId": "145751285", + "name": "A. Toker"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5601835", "name": "L. Cantley"}]}, {"paperId": "ef0a3f03e2588d7be3f08529a213f7d0dcf52001", + "externalIds": {"MAG": "1981552687", "DOI": "10.1074/JBC.270.25.14863", "CorpusId": + 42064743, "PubMed": "7541030"}, "corpusId": 42064743, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/ef0a3f03e2588d7be3f08529a213f7d0dcf52001", + "title": "The Phosphotyrosine Interaction Domain of SHC Recognizes Tyrosine-phosphorylated + NPXY Motif (*)", "abstract": "Reversible assembly of intracellular signaling + complexes is, in some cases, mediated by direct binding of a Src homology + 2 (SH2) domain of one protein to a phosphotyrosine moiety of another protein + (Cantley, L. C., Auger, K. R., Carpenter, C. L., Duckworth, B., Graziani, + A., Kapeller, R., and Soltoff, S.(1991) Cell 64, 281-302). Using a degenerate + phosphotyrosine-containing peptide library, we showed that individual SH2 + domains recognize phosphotyrosine in a specific sequence context to provide + fidelity in signaling (Songyang, Z., Shoelson, S. E., Chaudhuri, M., Gish, + G., Pawson, T., Haser, W. G., King, F., Roberts, T., Ratnofsky, S., Lechleider, + R. J., Neel, B. G., Birge, R. B., Fajardo, J. E., Chou, M. M., Hanafusa, H., + Schaffhausen, B., and Cantley, L. C.(1993) Cell 72, 767-778). Recently a second + type of phosphotyrosine interaction domain (PID) or phosphotyrosine-binding + domain (PTB) was discovered in the amino terminus of the SHC proto-oncoprotein + (Kavanaugh, W. M., and Williams, L.(1994) Science 266, 1862-1865; Blaikie, + P., Immanuel, D., Wu, J., Li, N., Yajnik, V., and Margolis, B.(1994) J. Biol. + Chem. 269, 32031-32034). Here we demonstrate, using a phosphotyrosine peptide + library, that the SHC PID domain preferentially binds to the sequence Asn-Pro-Xaa-phosphotyrosine. + This motif is in agreement with sequences at sites implicated in in vivo SHC + binding. These results indicate that while SH2 domains predominantly interact + with specific residues carboxyl-terminal of phosphotyrosine, the PID domain + has high specificity for residues amino-terminal of phosphotyrosine.", "venue": + "Journal of Biological Chemistry", "year": 1995, "referenceCount": 25, "citationCount": + 169, "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/270/25/14863.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1995-06-23", "journal": {"volume": "270", "pages": + "14863 - 14866", "name": "The Journal of Biological Chemistry"}, "authors": + [{"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "2075552899", + "name": "Benjamin Margolis"}, {"authorId": "2073353181", "name": "M. Chaudhuri"}, + {"authorId": "4790900", "name": "S. Shoelson"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "efabeb657bb3df1f9012940f7bae1aa4d9080cae", "externalIds": + {"MAG": "1999405592", "DOI": "10.1074/JBC.270.10.5130", "CorpusId": 6374320, + "PubMed": "7890622"}, "corpusId": 6374320, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/efabeb657bb3df1f9012940f7bae1aa4d9080cae", + "title": "Phosphatidylinositol 4,5-Bisphosphate Synthesis Is Required for + Activation of Phospholipase D in U937 Cells (*)", "abstract": "Phospholipase + D (PLD) has been implicated in signal transduction and membrane traffic. We + have previously shown that phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) + stimulates in vitro partially purified brain membrane PLD activity, defining + a novel function of PtdIns-4,5-P2 as a PLD cofactor. In the present study + we extend these observations to permeabilized U937 cells. In these cells, + the activation of PLD by guanosine 5\u2032-3-O-(thio)triphosphate (GTP\u03b3S) + is greatly potentiated by MgATP. We have utilized this experimental system + to test the hypothesis that MgATP potentiates PLD activation by G proteins + because it is required for PtdIns-4,5-P2 synthesis by phosphoinositide kinases. + As expected, MgATP was absolutely required for maintaining elevated phosphatidylinositol + 4-phosphate (PtdIns-4-P) and PtdIns-4,5-P2 levels in the permeabilized cells. + In the presence of MgATP, GTP\u03b3S further elevated the levels of the phosphoinositides. + The importance of PtdIns-4,5-P2 for PLD activation was examined by utilizing + a specific inhibitory antibody directed against phosphatidylinositol 4-kinase + (PtdIns 4-kinase), the enzyme responsible for the first step in the synthesis + of PtdIns-4,5-P2. Anti-PtdIns 4-kinase completely inhibited PtdIns 4-kinase + activity in vitro and reduced by 75-80% PtdIns-4-P and PtdIns-4,5-P2 levels + in the permeabilized cells. In parallel, the anti-PtdIns 4-kinase fully inhibited + the activation of PLD by GTP\u03b3S and caused a 60% inhibition of PLD activation + by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, indicating that + elevated PtdIns-4,5-P2 levels are required for PLD activation. This conclusion + is supported by the fact that neomycin, a high affinity ligand of PtdIns-4,5-P2, + also blocked PLD activation. Furthermore, the activity of PLD in U937 cell + lysate was stimulated by PtdIns-4,5-P2 in a dose-dependent manner. The current + results indicate that PtdIns-4,5-P2 synthesis is required for PLD activation + in permeabilized U937 cells and strongly support the proposed function of + PtdIns-4,5-P2 as a cofactor for PLD. In addition, the results further establish + PtdIns-4,5-P2 as a key component in the generation of second messengers via + multiple pathways including phosphoinositidephospholipase C, phosphoinositide + 3-kinase and PLD.", "venue": "Journal of Biological Chemistry", "year": 1995, + "referenceCount": 60, "citationCount": 106, "influentialCitationCount": 2, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.jbc.org/article/S0021925818947277/pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1995-03-10", "journal": {"volume": "270", "pages": "5130 + - 5135", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "1960212", "name": "P. Pertile"}, {"authorId": "6319769", "name": "M. Liscovitch"}, + {"authorId": "7626687", "name": "V. Chalifa"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "f6ce2aca171907adfcab889d4e90eb8666a389da", "externalIds": + {"MAG": "1980344230", "DOI": "10.1074/JBC.270.13.7111", "CorpusId": 19287811, + "PubMed": "7535767"}, "corpusId": 19287811, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/f6ce2aca171907adfcab889d4e90eb8666a389da", + "title": "Heregulin Stimulates Mitogenesis and Phosphatidylinositol 3-Kinase + in Mouse Fibroblasts Transfected with erbB2/neu and erbB3(*)", "abstract": + "Heregulin (HRG) is a pluripotent growth factor that can stimulate the growth + of some human mammary tumor cells and the differentiation of others. Two members + of the epidermal growth factor receptor family of receptor/tyrosine kinases, + p180erbB3 and p180erbB4, serve as receptors for the HRG ligand. While HRG + appears to be capable of stimulating the autophosphorylation activity of p180erbB4, + the co-expression of p185erbC2erbC2neu with p180erbB3 is necessary for the + HRG-stimulated tyrosine phosphorylation of both of these receptors. On the + basis of the sequences surrounding their putative tyrosine phosphorylation + sites, we predict that the different HRG-responsive receptors couple to different + intracellular SH2 domain-containing proteins. Hence, the different receptors + may mediate different cellular responses to the HRG ligand. In the present + study we show that HRG\u03b21 is mitogenic for erbB3-transfected DHFR/G8 cells, + an NIH3T3 mouse fibroblast derivative that overexpresses p185erbC2neu. HRG + stimulated the incorporation of [3H]thymidine into the DNA of these cells + with an EC50 of 70 \u00b1 7 pM. HRG was not mitogenic for parental DHFR/G8 + cells that do not express the ErbB3 protein. Phosphatidylinositol (PI) 3-kinase, + an enzyme believed to be important in cellular growth regulation by growth + factors and oncogenes, is predicted to couple to tyrosine-phosphorylated ErbB3. + We observed that HRG stimulated the association of PI 3-kinase with both p185erbC2neu + and ErbB3 in transfected DHFR/G8 cells, but not in the parental cell line. + We conclude that the ErbB3 protein is capable of mediating a proliferative + response of fibroblasts to HRG, and that the activation of PI 3-kinase is + an integral part of the growth signaling mechanism.", "venue": "Journal of + Biological Chemistry", "year": 1995, "referenceCount": 24, "citationCount": + 148, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "http://www.jbc.org/content/270/13/7111.full.pdf", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1995-03-31", "journal": {"volume": "270", "pages": "7111 + - 7116", "name": "The Journal of Biological Chemistry"}, "authors": [{"authorId": + "145331905", "name": "K. Carraway"}, {"authorId": "4324390", "name": "S. Soltoff"}, + {"authorId": "48917515", "name": "A. Diamonti"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "fc124a811d0f33a6f1a21bae79b3b6b33f9f6c4b", "externalIds": + {"CorpusId": 39020971, "PubMed": "7592789"}, "corpusId": 39020971, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/fc124a811d0f33a6f1a21bae79b3b6b33f9f6c4b", + "title": "Phosphoinositide 3-kinase binds constitutively to alpha/beta-tubulin + and binds to gamma-tubulin in response to insulin.", "abstract": "Recently + we reported the localization of phosphoinositide 3-kinase (PI 3-kinase) by + immunofluorescence to microtubule bundles and the centrosome (Kapeller, R., + Chakrabarti, R., Cantley, L., Fay, F., and Corvera, S. (1993) Mol. Cell. Biol. + 13, 6052-6063). In complementary experiments we used the recombinant p85 subunit + of PI 3-kinase to identify proteins that associate with phosphoinositide 3-kinase + and found that phosphoinositide 3-kinase associates with alpha/beta-tubulin. + The association occurs in vivo but was not significantly affected by growth + factor stimulation. We localized the region of p85 that interacts with alpha/beta-tubulin + to the inter-SH2 domain. These results support the immunofluorescence data + and show that p85 directly associates with alpha/beta-tubulin. We then determined + whether phosphoinositide 3-kinase associates with gamma-tubulin. We found + a dramatic growth factor-dependent association of phosphoinositide 3-kinase + with gamma-tubulin. Phosphoinositide 3-kinase associates with gamma-tubulin + in response to insulin and, to a lesser extent, in response to platelet-derived + growth factor. Neither epidermal growth factor nor nerve growth factor treatment + of cells results in association of phosphoinositide 3-kinase and gamma-tubulin. + Phosphoinositide 3-kinase is also immunoprecipitated with antibodies to pericentrin + in response to insulin, indicating that phosphoinositide 3-kinase is recruited + to the centrosome. Neither phosphoinositide 3-kinase activity, nor intact + microtubules are necessary for the association. Treatment of cells with 0.5 + M NaCl dissociates gamma-tubulin from the centrosome and disrupts the association + of phosphoinositide 3-kinase with pericentrin, but not gamma-tubulin. Recombinant + p85 binds to gamma-tubulin from both insulin stimulated and quiescent cells. + These results suggest that the association of phosphoinositide 3-kinase with + gamma-tubulin is direct. These data suggest that phosphoinositide 3-kinase + may be involved in regulating microtubule responses to insulin and platelet-derived + growth factor.", "venue": "Journal of Biological Chemistry", "year": 1995, + "referenceCount": 0, "citationCount": 50, "influentialCitationCount": 5, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], "publicationDate": + null, "journal": {"volume": "270 43", "pages": "\n 25985-91\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "2028875", + "name": "R. Kapeller"}, {"authorId": "145751285", "name": "A. Toker"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2972505", "name": "C. Carpenter"}]}, + {"paperId": "02af5861f3fb4ea9c1020bc9496e788927d66d15", "externalIds": {"MAG": + "1951853856", "DOI": "10.1128/mcb.14.11.7466-7475.1994", "CorpusId": 21929638, + "PubMed": "7935461"}, "corpusId": 21929638, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/02af5861f3fb4ea9c1020bc9496e788927d66d15", + "title": "Microinjection of the SH2 domain of the 85-kilodalton subunit of + phosphatidylinositol 3-kinase inhibits insulin-induced DNA synthesis and c-fos + expression", "abstract": "We have investigated the functional role of the + SH2 domain of the 85-kDa subunit (p85) of the phosphatidylinositol 3-kinase + in the insulin signal transduction pathway. Microinjection of a bacterial + fusion protein containing the N-terminal SH2 domain of p85 inhibited insulin- + and other growth factor-induced DNA synthesis by 90% and c-fos protein expression + by 80% in insulin-responsive rat fibroblasts. The specificity of the fusion + protein was examined by in vitro precipitation experiments, which showed that + the SH2 domain of p85 can independently associate with both insulin receptor + substrate 1 and the insulin receptor itself in the absence of detectable binding + to other phosphoproteins. The microinjection results were confirmed through + the use of an affinity-purified antibody directed against p85, which gave + the same phenotype. Additional studies were carried out in another cell line + expressing mutant insulin receptors which lack the cytoplasmic tyrosine residues + with which p85 interacts. Microinjection of the SH2 domain fusion protein + also inhibited insulin signaling in these cells, suggesting that association + of p85 with insulin receptor substrate 1 is a key element in insulin-mediated + cell cycle progression. In addition, coinjection of purified p21ras protein + with the p85 fusion protein or the antibody restored DNA synthesis, suggesting + that ras function is either downstream or independent of p85 SH2 domain interaction.", + "venue": "Molecular and Cellular Biology", "year": 1994, "referenceCount": + 49, "citationCount": 133, "influentialCitationCount": 4, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc359282?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-11-01", "journal": {"volume": "14", "pages": "7466 + - 7475", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "3605422", "name": "B. Jhun"}, {"authorId": "35346192", "name": "D. Rose"}, + {"authorId": "3485202", "name": "B. Seely"}, {"authorId": "4109960", "name": + "L. Rameh"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "33225327", + "name": "A. Saltiel"}, {"authorId": "2726044", "name": "J. Olefsky"}]}, {"paperId": + "0b2ff8a70ccdb925be535b6bb72a670e4b0b585b", "externalIds": {"MAG": "2014111401", + "DOI": "10.1073/PNAS.91.17.8132", "CorpusId": 43317619, "PubMed": "8058768"}, + "corpusId": 43317619, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/0b2ff8a70ccdb925be535b6bb72a670e4b0b585b", + "title": "Insect cell-expressed p180erbB3 possesses an impaired tyrosine kinase + activity.", "abstract": "Protein kinases share a number of highly conserved + or invariant amino acid residues in their catalytic domains, suggesting that + these residues are necessary for kinase activity. In p180erbB3, a receptor + tyrosine kinase belonging to the epidermal growth factor (EGF) receptor subfamily, + three of these residues are altered, suggesting that this protein might have + an impaired protein tyrosine kinase activity. To test this hypothesis, we + have expressed human EGF receptor and bovine p180erbB3 in insect cells via + baculovirus infection and have compared their autophosphorylation and substrate + phosphorylation activities. We have found that, while the EGF receptor readily + undergoes EGF-stimulated autophosphorylation and catalyzes the incorporation + of phosphate into the model substrates (E4Y1)n (random 4:1 copolymer of glutamic + acid and tyrosine) and GST-p85 (glutathione S-transferase fusion protein with + the 85-kDa subunit of phosphatidylinositol 3-kinase), p180erbB3 autophosphorylation + and substrate phosphorylation are at least 2 orders of magnitude less efficient. + However, p180erbB3 is capable of binding the ATP analog 5''-p-fluorosulfonylbenzoyladenosine, + indicating that the lack of observed kinase activity is probably not due to + nonfunctional or denatured receptors expressed by the insect cells. On the + basis of these results, we propose that p180erbB3 possesses an impaired intrinsic + tyrosine kinase activity.", "venue": "Proceedings of the National Academy + of Sciences of the United States of America", "year": 1994, "referenceCount": + 4, "citationCount": 740, "influentialCitationCount": 17, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc44559?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "1994-08-16", "journal": {"volume": + "91 17", "pages": "\n 8132-6\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "47873744", "name": "P. M. Guy"}, {"authorId": "4977593", "name": + "J. Platko"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4142168", "name": "R. Cerione"}, {"authorId": "145331905", "name": "K. Carraway"}]}, + {"paperId": "1805a0c296c4ca2bbb6e82c96a79ba18d1672272", "externalIds": {"MAG": + "1488828742", "DOI": "10.1016/s0021-9258(17)36789-3", "CorpusId": 19998792, + "PubMed": "8188716"}, "corpusId": 19998792, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/1805a0c296c4ca2bbb6e82c96a79ba18d1672272", + "title": "The erbB3 gene product is a receptor for heregulin.", "abstract": + null, "venue": "Journal of Biological Chemistry", "year": 1994, "referenceCount": + 0, "citationCount": 353, "influentialCitationCount": 11, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1994-05-13", "journal": {"volume": + "269 19", "pages": "\n 14303-6\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "145331905", "name": "K. + Carraway"}, {"authorId": "152442893", "name": "M. Sliwkowski"}, {"authorId": + "5465680", "name": "R. Akita"}, {"authorId": "4977593", "name": "J. Platko"}, + {"authorId": "47873744", "name": "P. M. Guy"}, {"authorId": "3622547", "name": + "A. Nuijens"}, {"authorId": "48917515", "name": "A. Diamonti"}, {"authorId": + "4749203", "name": "R. Vandlen"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4142168", "name": "R. Cerione"}]}, {"paperId": "25e8f1904e4f8b6daa0b912ef121d2f6573eb9cc", + "externalIds": {"MAG": "1999450178", "DOI": "10.1016/S0960-9822(00)00221-9", + "CorpusId": 7507217, "PubMed": "7874496"}, "corpusId": 7507217, "publicationVenue": + {"id": "9469269e-53d7-4955-b1a5-17a75bee7634", "name": "Current Biology", + "type": "journal", "alternate_names": ["Curr Biology"], "issn": "0960-9822", + "url": "http://www.current-biology.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/09609822"]}, + "url": "https://www.semanticscholar.org/paper/25e8f1904e4f8b6daa0b912ef121d2f6573eb9cc", + "title": "Use of an oriented peptide library to determine the optimal substrates + of protein kinases", "abstract": null, "venue": "Current Biology", "year": + 1994, "referenceCount": 28, "citationCount": 630, "influentialCitationCount": + 24, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1994-11-01", "journal": {"volume": "4", "pages": "973-982", "name": "Current + Biology"}, "authors": [{"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": + "7926608", "name": "S. Blechner"}, {"authorId": "6607412", "name": "N. Hoagland"}, + {"authorId": "4939757", "name": "M. Hoekstra"}, {"authorId": "1400810799", + "name": "H. Piwnica-Worms"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "3113a02bd76016ac6c88fb326844e23e8a962e6f", "externalIds": {"MAG": + "1963852241", "DOI": "10.1016/0092-8674(94)90148-1", "CorpusId": 5489016, + "PubMed": "8181054"}, "corpusId": 5489016, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/3113a02bd76016ac6c88fb326844e23e8a962e6f", + "title": "Lipid second messengers", "abstract": null, "venue": "Cell", "year": + 1994, "referenceCount": 33, "citationCount": 363, "influentialCitationCount": + 9, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Computer Science", + "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "1994-05-06", "journal": {"volume": "77", "pages": "329-334", + "name": "Cell"}, "authors": [{"authorId": "6319769", "name": "M. Liscovitch"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "3459757224680a407174df97d4daa63c83bc10af", + "externalIds": {"MAG": "1981108516", "DOI": "10.1016/0092-8674(94)90564-9", + "CorpusId": 39726384, "PubMed": "8033211"}, "corpusId": 39726384, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/3459757224680a407174df97d4daa63c83bc10af", + "title": "A neu acquaintance for ErbB3 and ErbB4: A role for receptor heterodimerization + in growth signaling", "abstract": null, "venue": "Cell", "year": 1994, "referenceCount": + 19, "citationCount": 641, "influentialCitationCount": 22, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": "1994-07-15", "journal": + {"volume": "78", "pages": "5-8", "name": "Cell"}, "authors": [{"authorId": + "145331905", "name": "K. Carraway"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "5518bfe6f1d2cc2195a4e509d42941edbb6f66a8", "externalIds": {"MAG": + "1978635034", "DOI": "10.1128/mcb.14.9.6372-6385.1994", "CorpusId": 11180518, + "PubMed": "7520528"}, "corpusId": 11180518, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/5518bfe6f1d2cc2195a4e509d42941edbb6f66a8", + "title": "Physical and functional interactions between SH2 and SH3 domains + of the Src family protein tyrosine kinase p59fyn", "abstract": "The Src family + protein tyrosine kinases participate in signalling through cell surface receptors + that lack intrinsic tyrosine kinase domains. All nine members of this family + possess adjacent Src homology (SH2 and SH3) domains, both of which are essential + for repression of the enzymatic activity. The repression is mediated by binding + between the SH2 domain and a C-terminal phosphotyrosine, and the SH3 domain + is required for this interaction. However, the biochemical basis of functional + SH2-SH3 interaction is unclear. Here, we demonstrate that when the SH2 and + SH3 domains of p59fyn (Fyn) were present as adjacent domains in a single protein, + binding of phosphotyrosyl peptides and proteins to the SH2 domain was enhanced, + whereas binding of a subset of cellular polypeptide ligands to the SH3 domain + was decreased. An interdomain communication was further revealed by occupancy + with domain-specific peptide ligands: occupancy of the SH3 domain with a proline-rich + peptide enhanced phosphotyrosine binding to the linked SH2 domain, and occupancy + of the SH2 domain with phosphotyrosyl peptides enhanced binding of certain + SH3-specific cellular polypeptides. Second, we demonstrate a direct binding + between purified SH2 and SH3 domains of Fyn and Lck Src family kinases. Heterologous + binding between SH2 and SH3 domains of closely related members of the Src + family, namely, Fyn, Lck, and Src, was also observed. In contrast, Grb2, Crk, + Abl, p85 phosphatidylinositol 3-kinase, and GTPase-activating protein SH2 + domains showed lower or no binding to Fyn or Lck SH3 domains. SH2-SH3 binding + did not require an intact phosphotyrosine binding pocket on the SH2 domain; + however, perturbations of the SH2 domain induced by specific high-affinity + phosphotyrosyl peptide binding abrogated binding of the SH3 domain. SH3-SH2 + binding was observed in the presence of proline-rich peptides or when a point + mutation (W119K) was introduced in the putative ligand-binding pouch of the + Fyn SH3 domain, although these treatments completely abolished the binding + to p85 phosphatidylinositol 3-kinase and other SH3-specific polypeptides. + These biochemical SH2-SH3 interactions suggest novel mechanisms of regulating + the enzymatic activity of Src kinases and their interactions with other proteins.", + "venue": "Molecular and Cellular Biology", "year": 1994, "referenceCount": + 87, "citationCount": 60, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc359163?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-09-01", "journal": {"volume": "14", "pages": "6372 + - 6385", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "50086870", "name": "G. Panchamoorthy"}, {"authorId": "152932875", "name": + "T. Fukazawa"}, {"authorId": "37494394", "name": "L. Stolz"}, {"authorId": + "98763489", "name": "G. Payne"}, {"authorId": "4061084", "name": "K. Reedquist"}, + {"authorId": "4790900", "name": "S. Shoelson"}, {"authorId": "6731027", "name": + "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "1929648539", "name": "C. Walsh"}, {"authorId": "145119394", "name": "H. Band"}]}, + {"paperId": "5953509475b9ccc9d766d75142183840c328ba94", "externalIds": {"MAG": + "1591614032", "DOI": "10.1016/s0021-9258(19)61989-7", "CorpusId": 36149088, + "PubMed": "7961848"}, "corpusId": 36149088, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/5953509475b9ccc9d766d75142183840c328ba94", + "title": "Cloning and characterization of a human phosphatidylinositol 4-kinase.", + "abstract": null, "venue": "Journal of Biological Chemistry", "year": 1994, + "referenceCount": 0, "citationCount": 80, "influentialCitationCount": 5, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-11-18", "journal": {"volume": "269 46", "pages": + "\n 28878-84\n ", "name": "The Journal of biological chemistry"}, + "authors": [{"authorId": "2107344210", "name": "K. Wong"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "6886cf242da4640818da5e32fc99eae43f67e7b6", + "externalIds": {"MAG": "2156475226", "DOI": "10.1002/BIES.950160810", "CorpusId": + 39196874, "PubMed": "8086005"}, "corpusId": 39196874, "publicationVenue": + {"id": "d0f8ce9f-9934-4c7b-aad8-7b2bfcf812c1", "name": "Bioessays", "type": + "journal", "alternate_names": ["BioEssays"], "issn": "0265-9247", "url": "http://www.bioessays-journal.com/", + "alternate_urls": ["http://www3.interscience.wiley.com/cgi-bin/jtoc/34201/", + "http://www3.interscience.wiley.com/cgi-bin/jhome/109911273", "http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-1878", + "https://onlinelibrary.wiley.com/journal/15211878"]}, "url": "https://www.semanticscholar.org/paper/6886cf242da4640818da5e32fc99eae43f67e7b6", + "title": "Phosphatidylinositol 3\u2010kinase", "abstract": "Currently, a central + question in biology is how signals from the cell surface modulate intracellular + processes. In recent years phosphoinositides have been shown to play a key + role in signal transduction. Two phosphoinositide pathways have been characterized, + to date. In the canonical phosphoinositide turnover pathway, activation of + phosphatidylinositol\u2010specific phospholipase C results in the hydrolysis + of phosphatidylinositol 4,5\u2010bisphospate and the generation of two second + messengers, inositol 1,4,5\u2010trisphosphate and diacylglycerol. The 3\u2010phosphoinositide + pathway involves protein\u2010tyrosine kinase\u2010mediated recruitment and + activation of phosphatidylinositol 3\u2010kinase, resulting in the production + of phosphatidylinositol 3,4\u2010bisphosphate and phosphatidylinositol 3,4,5\u2010trisphosphate. + The 3\u2010phosphoinositides are not substrates of any known phospholipase + C, are not components of the canonical phosphoinositide turnover pathway, + and may themselves act as intracellular mediators. The 3\u2010phosphoinositide + pathway has been implicated in growth factor\u2010dependent mitogenesis, membrane + ruffling and glucose uptake. Furthermore the homology of the yeast vps34 with + the mammalian phosphatidylinositol 3\u2010kinase has suggested a role for + this pathway in vesicular trafficking.", "venue": "Bioessays", "year": 1994, + "referenceCount": 87, "citationCount": 772, "influentialCitationCount": 27, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["Review", + "JournalArticle"], "publicationDate": "1994-08-01", "journal": {"volume": + "16", "name": "BioEssays"}, "authors": [{"authorId": "2028875", "name": "R. + Kapeller"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "6ce9fb2dfb1334b47cd8abc0157f251240ef34c7", + "externalIds": {"PubMedCentral": "2191364", "MAG": "2015366690", "DOI": "10.1084/JEM.179.2.551", + "CorpusId": 15400516, "PubMed": "8294866"}, "corpusId": 15400516, "publicationVenue": + {"id": "7d071626-1aa2-4dad-a259-bcccedccf44d", "name": "Journal of Experimental + Medicine", "type": "journal", "alternate_names": ["J Exp Med"], "issn": "0022-1007", + "url": "http://www.jem.org/"}, "url": "https://www.semanticscholar.org/paper/6ce9fb2dfb1334b47cd8abc0157f251240ef34c7", + "title": "Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA- + ligand interaction", "abstract": "Induced activation of protein tyrosine kinase(s) + is a central event in signal transduction mediated via the low affinity receptor + for IgG (Fc gamma RIIIA, CD16) in natural killer (NK) cells. Tyrosine phosphorylation + may affect the function of several protein directly, or indirectly by inducing + their association with other tyrosine phosphorylated proteins. Here, we report + that Fc gamma RIII stimulation induces activation of phosphatidylinositol + (PI)-3 kinase in NK cells. Phosphotyrosine immunoprecipitates from Fc gamma + RIII-stimulated NK cells contain PI-kinase activity and PI-3 kinase can be + directly precipitated from them. Conversely, a series of tyrosine-phosphorylated + proteins is coprecipitated with PI-3 kinase from the stimulated, but not from + control cells. Analogous results obtained using Jurkat T cells expressing + transfected Fc gamma RIIIA alpha ligand binding chain in association with + gamma 2 or zeta 2 homodimers indicate that both complexes transduce this effect, + although the Fc gamma RIIIA-zeta 2 complexes do so with greater efficiency. + Accumulation of phosphoinositide D3 phosphorylated products in stimulated + cells confirms PI-3 kinase activation, indicating the participation of this + enzyme in Fc gamma RIIIA-mediated signal transduction.", "venue": "Journal + of Experimental Medicine", "year": 1994, "referenceCount": 47, "citationCount": + 91, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "http://jem.rupress.org/content/179/2/551.full.pdf", "status": null}, + "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-02-01", "journal": {"volume": "179", "pages": "551 + - 558", "name": "The Journal of Experimental Medicine"}, "authors": [{"authorId": + "152590000", "name": "P. Kanakaraj"}, {"authorId": "21162853", "name": "B. + Duckworth"}, {"authorId": "1706855", "name": "L. Azzoni"}, {"authorId": "144496973", + "name": "M. Kamoun"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5893025", "name": "B. Perussia"}]}, {"paperId": "6f6e6b2617c168e176c74f3635fa940cfad7b1fa", + "externalIds": {"MAG": "2154060541", "DOI": "10.1073/PNAS.91.7.2834", "CorpusId": + 25831434, "PubMed": "8146197"}, "corpusId": 25831434, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/6f6e6b2617c168e176c74f3635fa940cfad7b1fa", + "title": "T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol + 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.", "abstract": "The T-cell + antigen CD28 provides a costimulatory signal that is required for T-cell proliferation. + T-cell receptor zeta/CD3 engagement without CD28 ligation leads to a state + of nonresponsiveness/anergy, thereby implicating CD28 in the control of peripheral + tolerance to foreign antigens or tumors. A key unresolved question has concerned + the mechanism by which CD28 generates intracellular signals. Phosphatidylinositol + 3-kinase (PI 3-kinase) is a lipid kinase with Src-homology 2 (SH2) domain(s) + that binds to the platelet-derived growth factor receptor (PDGF-R), an interaction + that is essential for signaling by growth factor. In this study, we demonstrate + that CD28 binds to PI 3-kinase by means of a Y(P)MXM motif within its cytoplasmic + tail. CD28-associated PI 3-kinase was detected by lipid kinase and HPLC analysis + as well as by reconstitution experiments with baculoviral-expressed p85 subunit + of PI 3-kinase. CD28 bound directly to the p85 subunit without the need for + the associated p110 subunit. Site-directed mutagenesis and peptide competition + analysis using Y(P)-MXM-containing peptides showed that PI 3-kinase bound + to a Y(P)MXM motif within the CD28 cytoplasmic tail (residues 191-194). Mutation + of the Y191 within the motif resulted in a complete loss of binding, while + mutation of M194 caused partial loss of binding. Binding analysis showed that + the CD28 Y(P)-MXM motif bound to the p85 C- and N-terminal SH2 domains with + an affinity comparable to that observed for PDGF-R and insulin receptor substrate + 1. In terms of signaling, CD28 ligation induced a dramatic increase in the + recruitment and association of PI 3-kinase with the receptor. CD28 is likely + to use PI 3-kinase as the second signal leading to T-cell proliferation, an + event with implications for anergy and peripheral T-cell tolerance.", "venue": + "Proceedings of the National Academy of Sciences of the United States of America", + "year": 1994, "referenceCount": 4, "citationCount": 295, "influentialCitationCount": + 7, "isOpenAccess": true, "openAccessPdf": {"url": "http://www.pnas.org/content/91/7/2834.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1994-03-29", "journal": {"volume": + "91 7", "pages": "\n 2834-8\n ", "name": "Proceedings of the + National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "49084493", "name": "K. Prasad"}, {"authorId": "2107739977", + "name": "Y. Cai"}, {"authorId": "3982584", "name": "M. Raab"}, {"authorId": + "21162853", "name": "B. Duckworth"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4790900", "name": "S. Shoelson"}, {"authorId": "3745275", "name": + "C. Rudd"}]}, {"paperId": "7823c73afb131f7ca66561cdfc794738e60749bf", "externalIds": + {"MAG": "1643628872", "DOI": "10.1016/s0021-9258(18)31643-0", "CorpusId": + 7153868, "PubMed": "7798235"}, "corpusId": 7153868, "publicationVenue": {"id": + "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological Chemistry", + "type": "journal", "alternate_names": ["J Biological Chem"], "issn": "0021-9258", + "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", "alternate_urls": + ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": "https://www.semanticscholar.org/paper/7823c73afb131f7ca66561cdfc794738e60749bf", + "title": "Activation of protein kinase C family members by the novel polyphosphoinositides + PtdIns-3,4-P2 and PtdIns-3,4,5-P3.", "abstract": null, "venue": "Journal of + Biological Chemistry", "year": 1994, "referenceCount": 5, "citationCount": + 515, "influentialCitationCount": 13, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-12-23", "journal": {"volume": "269 51", "pages": + "\n 32358-67\n ", "name": "The Journal of biological chemistry"}, + "authors": [{"authorId": "145751285", "name": "A. Toker"}, {"authorId": "2113465942", + "name": "M. Meyer"}, {"authorId": "145096349", "name": "K. K. Reddy"}, {"authorId": + "49877841", "name": "J. Falck"}, {"authorId": "1396882315", "name": "R. Aneja"}, + {"authorId": "49293205", "name": "S. Aneja"}, {"authorId": "90718565", "name": + "\u00c1. Parra"}, {"authorId": "49643658", "name": "D. Burns"}, {"authorId": + "8575754", "name": "L. M. Ballas"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "9782d9223b9ef77ba6a6630b6b5f2171935b9039", "externalIds": {"MAG": + "1979133563", "DOI": "10.1128/mcb.14.9.5929-5938.1994", "CorpusId": 18825095, + "PubMed": "8065326"}, "corpusId": 18825095, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/9782d9223b9ef77ba6a6630b6b5f2171935b9039", + "title": "Genetic analysis of a phosphatidylinositol 3-kinase SH2 domain reveals + determinants of specificity", "abstract": "Phosphatidylinositol 3-kinase is + an important element in both normal and oncogenic signal transduction. Polyomavirus + middle T antigen transforms cells in a manner depending on association of + its tyrosine 315 phosphorylation site with Src homology 2 (SH2) domains on + the p85 subunit of the phosphatidylinositol 3-kinase. Both nonselective and + site-directed mutagenesis have been used to probe the interaction of middle + T with the N-terminal SH2 domain of p85. Most of the 24 mutants obtained showed + reduced middle T binding. However, mutations that showed increased binding + were also found. Comparison of middle T binding to that of the platelet-derived + growth factor receptor showed that some mutations altered the specificity + of recognition by the SH2 domain. Mutations altering S-393, D-394, and P-395 + were shown to affect the ability of the SH2 domain to select peptides from + a degenerate phosphopeptide library. These results focus attention on the + role of the EF loop in the SH2 domain in determining binding selectivity at + the third position after the phosphotyrosine.", "venue": "Molecular and Cellular + Biology", "year": 1994, "referenceCount": 46, "citationCount": 27, "influentialCitationCount": + 2, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc359119?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-09-01", "journal": {"volume": "14", "pages": "5929 + - 5938", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "8945145", "name": "M. Yoakim"}, {"authorId": "102961250", "name": "W. Hou"}, + {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "2152668066", + "name": "Y. Liu"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4362128", "name": "B. Schaffhausen"}]}, {"paperId": "a07d06eba97b523bed133639b044d10cbd956272", + "externalIds": {"MAG": "2108246579", "DOI": "10.1128/mcb.14.6.3550-3558.1994", + "CorpusId": 41728331, "PubMed": "7515147"}, "corpusId": 41728331, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/a07d06eba97b523bed133639b044d10cbd956272", + "title": "ErbB3 is involved in activation of phosphatidylinositol 3-kinase + by epidermal growth factor", "abstract": "Conflicting results concerning the + ability of the epidermal growth factor (EGF) receptor to associate with and/or + activate phosphatidylinositol (PtdIns) 3-kinase have been published. Despite + the ability of EGF to stimulate the production of PtdIns 3-kinase products + and to cause the appearance of PtdIns 3-kinase activity in antiphosphotyrosine + immunoprecipitates in several cell lines, we did not detect EGF-stimulated + PtdIns 3-kinase activity in anti-EGF receptor immunoprecipitates. This result + is consistent with the lack of a phosphorylated Tyr-X-X-Met motif, the p85 + Src homology 2 (SH2) domain recognition sequence, in this receptor sequence. + The EGF receptor homolog, ErbB2 protein, also lacks this motif. However, the + ErbB3 protein has seven repeats of the Tyr-X-X-Met motif in the carboxy-terminal + unique domain. Here we show that in A431 cells, which express both the EGF + receptor and ErbB3, PtdIns 3-kinase coprecipitates with the ErbB3 protein + (p180erbB3) in response to EGF. p180erbB3 is also shown to be tyrosine phosphorylated + in response to EGF. In contrast, a different mechanism for the activation + of PtdIns 3-kinase in response to EGF occurs in certain cells (PC12 and A549 + cells). Thus, we show for the first time that ErbB3 can mediate EGF responses + in cells expressing both ErbB3 and the EGF receptor.", "venue": "Molecular + and Cellular Biology", "year": 1994, "referenceCount": 47, "citationCount": + 561, "influentialCitationCount": 36, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc358722?pdf=render", "status": null}, + "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-06-01", "journal": {"volume": "14", "pages": "3550 + - 3558", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "4324390", "name": "S. Soltoff"}, {"authorId": "145331905", "name": "K. Carraway"}, + {"authorId": "14615148", "name": "S. Prigent"}, {"authorId": "2071010729", + "name": "W. Gullick"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "acd3a27973c7d0258f7674048f6dcf947d37aa51", "externalIds": {"MAG": "2082839106", + "DOI": "10.1242/jcs.1994.Supplement_18.18", "CorpusId": 20160734, "PubMed": + "7533766"}, "corpusId": 20160734, "publicationVenue": {"id": "398b46b8-6014-4478-b7af-f477167f7bde", + "name": "Journal of Cell Science", "type": "journal", "alternate_names": ["J + Cell Sci"], "issn": "0021-9533", "url": "https://jcs.biologists.org/", "alternate_urls": + ["http://jcs.biologists.org/"]}, "url": "https://www.semanticscholar.org/paper/acd3a27973c7d0258f7674048f6dcf947d37aa51", + "title": "Specificity in recognition of phosphopeptides by src-homology 2 + domains", "abstract": "SUMMARY SH2 domains and SH3 domains, found in a number + of protein-tyrosine kinases and substrates of protein-tyrosine kinases, provide + specificity in downstream signaling. Both of these domains bind to relatively + short linear sequences of peptides to provide specific interactions between + proteins. The SH2 domains directly bind to phosphotyrosine residues of proteins + in a specific sequence context. We have devised a phosphopeptide library technique + that allows us to rapidly determine the sequence specificity of individual + SH2 domains on the basis of amino acids selected at position +1,+2 and +3 + C-terminal of the phosphotyrosine. The optimal motif for 22 distinct SH2 domains + has been determined and used to predict likely sites of in vivo interaction. + A second phosphopeptide library was devised in which the amino acids N-terminal + of the phosphotyrosine were also varied. The residues N-terminal of phosphotyrosine + had little influence on binding to the N-SH2 domain of the 85 kDa subunit + of phosphoinositide 3-kinase. These results indicate that for this SH2 domain, + specificity is determined by sequences carboxy-terminal of the phosphotyrosine + moiety. Knowledge of the specificity of SH2 domains allows predictions about + likely downstream targets on the basis of primary sequence of proteins. Some + of these predictions will be discussed.", "venue": "Journal of Cell Science", + "year": 1994, "referenceCount": 37, "citationCount": 65, "influentialCitationCount": + 4, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1994-01-01", "journal": {"volume": "1994", "pages": "121 - 126", "name": + "Journal of Cell Science"}, "authors": [{"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "6731027", "name": "Z. Songyang"}]}, {"paperId": "ace6bf58ba218fdb0fc63e3121a9ce79916cadcd", + "externalIds": {"MAG": "2021938232", "DOI": "10.1038/369502A0", "CorpusId": + 22767669, "PubMed": "7515480"}, "corpusId": 22767669, "publicationVenue": + {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/ace6bf58ba218fdb0fc63e3121a9ce79916cadcd", + "title": "SH2 domain specificity and activity modified by a single residue", + "abstract": null, "venue": "Nature", "year": 1994, "referenceCount": 31, "citationCount": + 187, "influentialCitationCount": 4, "isOpenAccess": true, "openAccessPdf": + {"url": "https://tspace.library.utoronto.ca/bitstream/1807/9433/3/Bidirectional%20signalling%20through%20the%20EPH.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1994-06-09", "journal": {"volume": "369", "pages": "502-505", + "name": "Nature"}, "authors": [{"authorId": "4055899", "name": "L. Mareng\u00e8re"}, + {"authorId": "6731027", "name": "Z. Songyang"}, {"authorId": "37993016", "name": + "G. Gish"}, {"authorId": "2955823", "name": "M. Schaller"}, {"authorId": "4756296", + "name": "J. Parsons"}, {"authorId": "47189623", "name": "M. Stern"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "50999462", "name": "T. Pawson"}]}, + {"paperId": "baaf3e797f22b0802fde0d70f1f16287f224afcf", "externalIds": {"MAG": + "2566159072", "DOI": "10.1016/s0021-9258(17)42115-6", "CorpusId": 12508185, + "PubMed": "8294442"}, "corpusId": 12508185, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/baaf3e797f22b0802fde0d70f1f16287f224afcf", + "title": "Identification of two SH3-binding motifs in the regulatory subunit + of phosphatidylinositol 3-kinase.", "abstract": null, "venue": "Journal of + Biological Chemistry", "year": 1994, "referenceCount": 3, "citationCount": + 142, "influentialCitationCount": 6, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle", "Study"], "publicationDate": "1994-01-21", + "journal": {"volume": "269 3", "pages": "\n 1927-33\n ", "name": + "The Journal of biological chemistry"}, "authors": [{"authorId": "2028875", + "name": "R. Kapeller"}, {"authorId": "49084493", "name": "K. Prasad"}, {"authorId": + "2694949", "name": "O. Janssen"}, {"authorId": "102961250", "name": "W. Hou"}, + {"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": "3745275", + "name": "C. Rudd"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d3f100a9bc1170e5609f4a4a42d8ebc0b2b06865", "externalIds": {"MAG": "59209658", + "CorpusId": 25413597, "PubMed": "8063770"}, "corpusId": 25413597, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/d3f100a9bc1170e5609f4a4a42d8ebc0b2b06865", + "title": "Novel function of phosphatidylinositol 4,5-bisphosphate as a cofactor + for brain membrane phospholipase D.", "abstract": "The activation of phospholipase + D (PLD) is a receptor-mediated event that has been implicated in signal transduction + and membrane traffic in eukaryotic cells. Little is known about the biochemical + and molecular properties of signal-activated PLDs, and none has been isolated. + Here we report that phosphatidylinositol 4,5-bisphosphate (PIP2) potently + stimulates brain membrane PLD activity in vitro in a highly specific manner. + PIP2 increases 10-fold the maximal activity of a partially purified PLD with + an EC50 of < 0.5 mol %. Other acidic phospholipids, including phosphatidylinositol + 4-phosphate, phosphatidylinositol, phosphatidylserine, and phosphatidic acid, + are completely or nearly ineffective. Neomycin, a high affinity ligand of + PIP2, inhibits membrane-bound PLD but has no effect on the activity of a detergent-solubilized + or partially purified enzyme. The addition of PIP2 restores the sensitivity + of partially purified PLD to neomycin inhibition, indicating that neomycin + blocks membrane PLD activity by binding to endogenous PIP2. These results + define a novel function of PIP2 as a cofactor for brain membrane PLD and suggest + that PIP2 synthesis and hydrolysis could be important determinants in regulating + PLD action in signal transduction and membrane transport.", "venue": "Journal + of Biological Chemistry", "year": 1994, "referenceCount": 2, "citationCount": + 267, "influentialCitationCount": 9, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", "Study"], + "publicationDate": "1994-08-26", "journal": {"volume": "269 34", "pages": + "\n 21403-6\n ", "name": "The Journal of biological chemistry"}, + "authors": [{"authorId": "6319769", "name": "M. Liscovitch"}, {"authorId": + "7626687", "name": "V. Chalifa"}, {"authorId": "1960212", "name": "P. Pertile"}, + {"authorId": "49751345", "name": "C. S. Chen"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "01b37b20b2a8a7cfce032a9189bbb48624187b04", "externalIds": + {"MAG": "2130716490", "DOI": "10.1128/mcb.13.3.1657-1665.1993", "CorpusId": + 37619916, "PubMed": "8382773"}, "corpusId": 37619916, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/01b37b20b2a8a7cfce032a9189bbb48624187b04", + "title": "A tightly associated serine/threonine protein kinase regulates phosphoinositide + 3-kinase activity", "abstract": "We identified a serine/threonine protein + kinase that is associated with and phosphorylates phosphoinositide 3-kinase + (PtdIns 3-kinase). The serine kinase phosphorylates both the 85- and 110-kDa + subunits of PtdIns 3-kinase and purifies with it from rat liver and immunoprecipitates + with antibodies raised to the 85-kDa subunit. Tryptic phosphopeptide maps + indicate that p85 from polyomavirus middle T-transformed cells is phosphorylated + in vivo at three sites phosphorylated in vitro by the associated serine kinase. + The 85-kDa subunit of PtdIns 3-kinase is phosphorylated in vitro on serine + at a stoichiometry of approximately 1 mol of phosphate per mol of p85. This + phosphorylation results in a three- to sevenfold decrease in PtdIns 3-kinase + activity. Dephosphorylation with protein phosphatase 2A reverses the inhibition. + This suggests that the association of protein phosphatase 2A with middle T + antigen may function to activate PtdIns 3-kinase.", "venue": "Molecular and + Cellular Biology", "year": 1993, "referenceCount": 39, "citationCount": 207, + "influentialCitationCount": 6, "isOpenAccess": true, "openAccessPdf": {"url": + "https://europepmc.org/articles/pmc359478?pdf=render", "status": null}, "fieldsOfStudy": + ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": + "external"}, {"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Computer Science", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1993-03-01", "journal": {"volume": "13", "pages": "1657 - 1665", "name": + "Molecular and Cellular Biology"}, "authors": [{"authorId": "2972505", "name": + "C. Carpenter"}, {"authorId": "6603909", "name": "K. Auger"}, {"authorId": + "21162853", "name": "B. Duckworth"}, {"authorId": "102961250", "name": "W. + Hou"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "0842ce9e31ee972259a0b342cea65e11ec18150b", + "externalIds": {"MAG": "115395656", "CorpusId": 6840736, "PubMed": "7683128"}, + "corpusId": 6840736, "publicationVenue": {"id": "55bed249-d30f-456b-9d2c-a51dc149cb7a", + "name": "Oncogene", "type": "journal", "issn": "0950-9232", "url": "http://www.nature.com/onc/", + "alternate_urls": ["http://www.nature.com/onc", "http://www.naturesj.com/onc/index.html"]}, + "url": "https://www.semanticscholar.org/paper/0842ce9e31ee972259a0b342cea65e11ec18150b", + "title": "Regulation of c-Src tyrosine kinase activity by the Src SH2 domain.", + "abstract": "The protein-tyrosine kinase activity of pp60c-src (c-Src) is + inhibited by phosphorylation of tyr527, within the c-Src c-terminal tail. + Genetic and biochemical data have suggested that this negative regulation + requires an intact Src homology 2 (SH2) domain. Since SH2 domains recognize + phosphotyrosine, it is possible that these two non-catalytic domains associate, + and thereby repress c-Src kinase activity. Consistent with this model, an + isolated Src SH2 domain expressed in bacteria as a GST fusion protein bound + in vitro to a synthetic phosphotyrosine-containing peptide modeled on the + C-terminal 13 residues of the c-Src tail. Binding was absolutely dependent + on phosphorylation of tyr527 in the tail peptide, and was modified by both + the length and sequence of the peptide. Competition experiments indicated + only a moderate binding affinity between the Src SH2 domain and the phosphorylated + tail. A distinct phosphotyrosine-containing peptide previously identified + as binding the Src SH2 domain with high affinity stimulated c-Src tyrosine + kinase activity in vitro, possibly by competing with the endogenous tail phosphorylation + site for binding to the SH2 domain. Indeed, this activation was competitively + inhibited by purified bacterial Src SH2 domain. These data provide direct + evidence that the c-Src tail has an intrinsic affinity for the Src SH2 domain, + and suggest that such an interaction in the intact molecule contributes to + maintaining c-Src in an inactive form.", "venue": "Oncogene", "year": 1993, + "referenceCount": 0, "citationCount": 210, "influentialCitationCount": 3, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1993-05-01", "journal": {"volume": + "8 5", "pages": "\n 1119-26\n ", "name": "Oncogene"}, "authors": + [{"authorId": "153201731", "name": "X. Liu"}, {"authorId": "3211107", "name": + "S. Brodeur"}, {"authorId": "37993016", "name": "G. Gish"}, {"authorId": "6731027", + "name": "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4734468", "name": "A. Laudano"}, {"authorId": "50999462", "name": "T. Pawson"}]}, + {"paperId": "23ab2836a31a3f5b4bda1b19a2ed65c5d84c5dff", "externalIds": {"MAG": + "2066040740", "DOI": "10.1016/0006-2952(93)90455-6", "CorpusId": 19952952, + "PubMed": "7684222"}, "corpusId": 19952952, "publicationVenue": {"id": "c2ed7282-3d57-4734-ac70-51f9bffc1368", + "name": "Biochemical Pharmacology", "type": "journal", "alternate_names": + ["Biochem Pharmacol"], "issn": "0006-2952", "alternate_issns": ["1356-1839"], + "url": "http://www.elsevier.com/locate/issn/00062952", "alternate_urls": ["http://www.elsevier.com/wps/find/journaldescription.cws_home/525454/description", + "http://www.sciencedirect.com/science/journal/00062952"]}, "url": "https://www.semanticscholar.org/paper/23ab2836a31a3f5b4bda1b19a2ed65c5d84c5dff", + "title": "Blockade of ATP binding site of P2 purinoceptors in rat parotid + acinar cells by isothiocyanate compounds.", "abstract": null, "venue": "Biochemical + Pharmacology", "year": 1993, "referenceCount": 20, "citationCount": 49, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1993-05-05", "journal": {"volume": + "45 9", "pages": "\n 1936-40\n ", "name": "Biochemical pharmacology"}, + "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "144664118", + "name": "M. McMillian"}, {"authorId": "3683975", "name": "B. Talamo"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "23f63abb380b90ea875c104eb3fbb0a7db11fde6", + "externalIds": {"MAG": "2164682544", "DOI": "10.1016/0092-8674(93)90404-E", + "CorpusId": 731207, "PubMed": "7680959"}, "corpusId": 731207, "publicationVenue": + {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", "name": "Cell", "type": "journal", + "alternate_names": ["La Cellule"], "issn": "0092-8674", "alternate_issns": + ["0008-8757"], "url": "https://www.cell.com/", "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/23f63abb380b90ea875c104eb3fbb0a7db11fde6", + "title": "SH2 domains recognize specific phosphopeptide sequences", "abstract": + null, "venue": "Cell", "year": 1993, "referenceCount": 53, "citationCount": + 2613, "influentialCitationCount": 49, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1993-03-12", "journal": {"volume": "72", "pages": "767-778", + "name": "Cell"}, "authors": [{"authorId": "2111144577", "name": "Songyang + Zhou"}, {"authorId": "4790900", "name": "S. Shoelson"}, {"authorId": "2073353181", + "name": "M. Chaudhuri"}, {"authorId": "37993016", "name": "G. Gish"}, {"authorId": + "50999462", "name": "T. Pawson"}, {"authorId": "4104149", "name": "W. Haser"}, + {"authorId": "2115046366", "name": "Fred King"}, {"authorId": "2053044498", + "name": "T. Roberts"}, {"authorId": "5982171", "name": "S. Ratnofsky"}, {"authorId": + "4551861", "name": "R. Lechleider"}, {"authorId": "2291271", "name": "B. Neel"}, + {"authorId": "3752444", "name": "R. Birge"}, {"authorId": "143676959", "name": + "J. Fajardo"}, {"authorId": "15675591", "name": "M. Chou"}, {"authorId": "1973946", + "name": "H. Hanafusa"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "38543d199605ce693325a85975f677cc068851b0", + "externalIds": {"MAG": "2236313857", "DOI": "10.1128/mcb.13.8.4648-4656.1993", + "CorpusId": 23389302, "PubMed": "7687742"}, "corpusId": 23389302, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/38543d199605ce693325a85975f677cc068851b0", + "title": "Identification and characterization of a high-affinity interaction + between v-Crk and tyrosine-phosphorylated paxillin in CT10-transformed fibroblasts", + "abstract": "The genome of avian sarcoma virus CT10 encodes a fusion protein + in which viral Gag sequences are fused to cellular Crk sequences containing + primarily Src homology 2 (SH2) and Src homology 3 (SH3) domains. Transformation + of chicken embryo fibroblasts (CEF) with the Gag-Crk fusion protein results + in the elevation of tyrosine phosphorylation on specific cellular proteins + with molecular weights of 130,000, 110,000, and 70,000 (p130, p110, and p70, + respectively), an event which has been correlated with cell transformation. + In this study, we have identified the 70-kDa tyrosine-phosphorylated protein + in CT10-transformed CEF (CT10-CEF) as paxillin, a cytoskeletal protein suggested + to be important for organizing the focal adhesion. Tyrosine-phosphorylated + paxillin was found to be complexed with v-Crk in vivo as evident from coimmunoprecipitation + studies. Moreover, a bacterially expressed recombinant glutathione S-transferase + (GST)-CrkSH2 fragment bound paxillin in vitro with a subnanomolar affinity, + suggesting that the SH2 domain of v-Crk is sufficient for binding. Mapping + of the sequence specificity of a GST-CrkSH2 fusion protein with a partially + degenerate phosphopeptide library determined a motif consisting of pYDXP, + and in competitive coprecipitation studies, an acetylated A(p)YDAPA hexapeptide + was able to quantitatively inhibit the binding of GST-CrkSH2 to paxillin and + p130, suggesting that it meets the minimal structural requirements necessary + for the interaction of CrkSH2 with physiological targets. To investigate the + mechanism by which v-Crk elevates the tyrosine phosphorylation of paxillin + in vivo, we have treated normal CEF and CT10-CEF with sodium vanadate to inhibit + protein tyrosine phosphatase activity. These data suggest that paxillin is + involved in a highly dynamic kinase-phosphatase interplay in normal CEF and + that v-Crk binding may interrupt this balance to increase the steady-state + level of tyrosine phosphorylation. By contrast, the 130-kDa protein was not + tyrosine phosphorylated upon vanadate treatment of normal CEF and only weakly + affected in the CT10-CEF, suggesting that a different mechanism may be involved + in its phosphorylation.", "venue": "Molecular and Cellular Biology", "year": + 1993, "referenceCount": 51, "citationCount": 257, "influentialCitationCount": + 11, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc360091?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1993-08-01", "journal": {"volume": + "13", "pages": "4648 - 4656", "name": "Molecular and Cellular Biology"}, "authors": + [{"authorId": "3752444", "name": "R. Birge"}, {"authorId": "143676959", "name": + "J. Fajardo"}, {"authorId": "4955594", "name": "C. Reichman"}, {"authorId": + "4790900", "name": "S. Shoelson"}, {"authorId": "6731027", "name": "Z. Songyang"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "1973946", "name": + "H. Hanafusa"}]}, {"paperId": "4cc1af566110f6cf0563cc6b25b20e22fcf29201", + "externalIds": {"MAG": "2118110409", "DOI": "10.1098/RSTB.1993.0132", "CorpusId": + 19832710, "PubMed": "7904344"}, "corpusId": 19832710, "publicationVenue": + {"id": "6de51a3e-86d6-4b08-92f5-a2a4a3a1c47b", "name": "Philosophical transactions + of the Royal Society of London. Series B, Biological sciences", "alternate_names": + ["Philos trans R Soc Lond Ser B Biological sci"], "issn": "0080-4622", "alternate_issns": + ["2054-0280"], "url": "http://www.jstor.org/action/showPublication?journalCode=philtranroyasoc2"}, + "url": "https://www.semanticscholar.org/paper/4cc1af566110f6cf0563cc6b25b20e22fcf29201", + "title": "Regulation of CD4-p56lck-associated phosphatidylinositol 3-kinase + (PI 3-kinase) and phosphatidylinositol 4-kinase (PI 4-kinase).", "abstract": + "CD4 serves as a receptor for MHC class II antigens and as a receptor for + the human immunodeficiency virus (HIV-1) viral coat protein gp120. It is coupled + to the protein-tyrosine kinase p56lck, an interaction necessary for an optimal + response of certain T cells to antigen. Although anti-CD4 crosslinking may + increase lck activity, the effects of HIV-1 gp120 have been controversial. + Activated protein-tyrosine kinases are known to associate with certain intracellular + proteins possessing src-homology regions (SH-2 domains) such as phosphatidylinositol + 3-kinase (PI 3-kinase). In this paper, we demonstrate that the CD4:p56lck + complex associates with significant amounts of phosphatidylinositol (PI) kinase + activity. High pressure liquid chromatographic (HPLC) analysis of the reaction + products demonstrated the presence of phosphatidylinositol 3-phosphate (PI + 3-P) and phosphatidylinositol 4-phosphate (PI 4-P), thus indicating that PI + 3 and PI 4 kinases associate with CD4-p56lck. The p85 subunit of PI 3-kinase + was also detected in anti-CD4 immunoprecipitates by immunoblotting with anti-p85 + antiserum. Significantly, p56lck binding to CD4 appears to be necessary for + the detection of lipid kinase activity associated with p56lck. Also, anti-HIV + gp120 and anti-CD4 crosslinking induced a 10-15-fold increase in levels of + both PI 3- and PI 4-kinase activity in anti-CD4 precipitates. Stimulation + of CD4-p56lck-linked PI kinases by crosslinked HIV-1 gp120 may play a role + in HIV-1-induced immune defects.", "venue": "Philosophical transactions of + the Royal Society of London. Series B, Biological sciences", "year": 1993, + "referenceCount": 27, "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1993-10-29", "journal": {"volume": "342 1299", "pages": + "\n 35-42\n ", "name": "Philosophical transactions of the + Royal Society of London. Series B, Biological sciences"}, "authors": [{"authorId": + "49084493", "name": "K. Prasad"}, {"authorId": "2028875", "name": "R. Kapeller"}, + {"authorId": "2694949", "name": "O. Janssen"}, {"authorId": "1400208976", + "name": "J. Duke-Cohan"}, {"authorId": "5014538", "name": "H. Repke"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3745275", "name": "C. Rudd"}]}, + {"paperId": "66b77a160b27aac1295bca2889e37801f678e38e", "externalIds": {"MAG": + "2092677752", "DOI": "10.1111/j.1476-5381.1993.tb12825.x", "CorpusId": 24479493, + "PubMed": "8448596"}, "corpusId": 24479493, "publicationVenue": {"id": "72dc4a68-546a-4211-947e-a9ef859d12ad", + "name": "British Journal of Pharmacology", "type": "journal", "alternate_names": + ["Br J Pharmacol"], "issn": "0007-1188", "url": "http://www.nature.com/bjp/index.html", + "alternate_urls": ["http://www.brjpharmacol.org/", "https://onlinelibrary.wiley.com/journal/14765381", + "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=282", + "http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476-5381/issues"]}, + "url": "https://www.semanticscholar.org/paper/66b77a160b27aac1295bca2889e37801f678e38e", + "title": "Two distinct cytosolic calcium responses to extracellular ATP in + rat parotid acinar cells", "abstract": "1 Increasing concentrations of ATP + (0.5 \u03bcm\u2010300 \u03bcm) produced a biphasic increase in intracellular + calcium concentration [Ca]i in rat parotid acinar cells, reflecting two distinct + Cai responses to extracellular ATP. 2 In the absence of Mg2+ (with 3 mm CaCl2 + in the buffer solution), the more sensitive response was maximal at 3\u20135 + \u03bcm and was not further increased by 30 \u03bcm ATP. This response to + ATP was not well maintained and was blocked by ADP (0.5 mm). A second, much + larger increase in Cai was observed on addition of 300 \u03bcm ATP. This larger + effect, which we have described previously, appears to be mediated by ATP4\u2013, + and was selectively reversed by 4,4\u2032\u2010di\u2010isothiocyanato\u2010dihydrostilbene\u20102,2\u2032\u2010disulphonate + as well as by high concentrations of \u03b1,\u03b2\u2010methylene ATP. 3 Among + ATP analogues, only the putative P2Z agonist, 3\u2032\u20100\u2010(4\u2010benzoyl)benzoyl\u2010ATP + distinguished between the two responses. This analogue was at least 10 fold + more potent than ATP in stimulating the ATP4\u2013\u2010response, but did + not evoke the more sensitive response. The agonist potency series for both + responses to ATP was identical for other analogues examined (ATP>ATP\u2010\u03b3S + = 2\u2010methylthio ATP (a P2y\u2010selective agonist) 72>ADP, ITP and \u03b1,\u03b2\u2010methylene + ATP (a P2X\u2010selective agonist)). 4 Although the effect of ATP4\u2013 could + best be characterized as a P2Z\u2010type purinoceptor response, this effect + was strongly and selectively blocked by reactive blue 2, a putative P2y\u2010purinoceptor + antagonist. Reactive blue 2 may bind to and block P2Z purinoceptors since + [\u03b332P]\u2010ATP binding to parotid cells was inhibited by this compound. + 5 In contrast to the response to ATP4\u2013, the more sensitive response to + ATP was potentiated by reactive blue 2 and was less affected by increases + in external Mg2+ and Ca2+. 6 Parasympathetic denervation selectively increased + the more sensitive response, suggesting that it may be physiologically regulated.", + "venue": "British Journal of Pharmacology", "year": 1993, "referenceCount": + 54, "citationCount": 61, "influentialCitationCount": 1, "isOpenAccess": true, + "openAccessPdf": {"url": "https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1476-5381.1993.tb12825.x", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1993-02-01", "journal": {"volume": "108", "name": + "British Journal of Pharmacology"}, "authors": [{"authorId": "144664118", + "name": "M. McMillian"}, {"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "2378702", "name": "R. Rudel"}, + {"authorId": "3683975", "name": "B. Talamo"}]}, {"paperId": "96e9ac3cbd6ee7e467ae6e775f65685dab63a555", + "externalIds": {"MAG": "112200190", "DOI": "10.1007/978-3-642-78247-3_20", + "CorpusId": 91547247}, "corpusId": 91547247, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/96e9ac3cbd6ee7e467ae6e775f65685dab63a555", + "title": "Role of Phosphatidylinositol 3-Kinase in Growth Factor and Oncogene + Signaling", "abstract": null, "venue": "", "year": 1993, "referenceCount": + 35, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "pages": "149-165", "name": ""}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "abdfaa470caa7657449ee7e6949a65d1ed213f6e", "externalIds": + {"MAG": "2104340409", "DOI": "10.1073/PNAS.90.15.7366", "CorpusId": 25434531, + "PubMed": "8394019"}, "corpusId": 25434531, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/abdfaa470caa7657449ee7e6949a65d1ed213f6e", + "title": "Src-homology 3 domain of protein kinase p59fyn mediates binding + to phosphatidylinositol 3-kinase in T cells.", "abstract": "The Src-related + tyrosine kinase p59fyn(T) plays an important role in the generation of intracellular + signals from the T-cell antigen receptor TCR zeta/CD3 complex. A key question + concerns the nature and the binding sites of downstream components that interact + with this Src-related kinase. p59fyn(T) contains Src-homology 2 and 3 domains + (SH2 and SH3) with a capacity to bind to intracellular proteins. One potential + downstream target is phosphatidylinositol 3-kinase (PI 3-kinase). In this + study, we demonstrate that anti-CD3 and anti-Fyn immunoprecipitates possess + PI 3-kinase activity as assessed by TLC and HPLC. Both free and receptor-bound + p59fyn(T) were found to bind to the lipid kinase. Further, our results indicate + that Src-related kinases have developed a novel mechanism to interact with + PI 3-kinase. Precipitation using GST fusion proteins containing Fyn SH2, SH3, + and SH2/SH3 domains revealed that PI 3-kinase bound principally to the SH3 + domain of Fyn. Fyn SH3 bound directly to the p85 subunit of PI 3-kinase as + expressed in a baculoviral system. Anti-CD3 crosslinking induced an increase + in the detection of Fyn SH3-associated PI 3-kinase activity. Thus PI 3-kinase + is a target of SH3 domains and is likely to play a major role in the signals + derived from the TCR zeta/CD3-p59fyn complex.", "venue": "Proceedings of the + National Academy of Sciences of the United States of America", "year": 1993, + "referenceCount": 0, "citationCount": 165, "influentialCitationCount": 1, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc47138?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1993-08-01", "journal": {"volume": + "90 15", "pages": "\n 7366-70\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "49084493", "name": "K. Prasad"}, {"authorId": "2694949", "name": + "O. Janssen"}, {"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": + "3982584", "name": "M. Raab"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "3745275", "name": "C. Rudd"}]}, {"paperId": "b3bc181e9fa491ccdc293374a6ac381961f37a02", + "externalIds": {"MAG": "1537485228", "DOI": "10.1016/s0021-9258(18)53589-4", + "CorpusId": 9178517, "PubMed": "8382694"}, "corpusId": 9178517, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/b3bc181e9fa491ccdc293374a6ac381961f37a02", + "title": "A murine genomic DNA fragment amplifies ouabain-induced Na,K-ATPase + alpha/beta-subunit mRNA up-regulation and confers ouabain resistance.", "abstract": + null, "venue": "Journal of Biological Chemistry", "year": 1993, "referenceCount": + 0, "citationCount": 4, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1993-02-25", "journal": {"volume": + "268 6", "pages": "\n 4126-33\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "48666973", "name": "X. M. + Zhou"}, {"authorId": "2056117768", "name": "M. J. Cunha"}, {"authorId": "48381149", + "name": "J. Epstein"}, {"authorId": "144579743", "name": "R. Levenson"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "5601835", "name": "L. Cantley"}]}, + {"paperId": "b5fba79e88954c8057574e8257a7dc92301cbe48", "externalIds": {"MAG": + "226520676", "DOI": "10.1002/j.1460-2075.1993.tb05929.x", "CorpusId": 29371814, + "PubMed": "8392933"}, "corpusId": 29371814, "publicationVenue": {"id": "b89f0ede-6fa8-4dd2-a8a7-f54695a00323", + "name": "EMBO Journal", "type": "journal", "alternate_names": ["The EMBO Journal", + "EMBO J"], "issn": "0261-4189", "url": "http://embojournal.npgjournals.com/", + "alternate_urls": ["http://emboj.embopress.org/"]}, "url": "https://www.semanticscholar.org/paper/b5fba79e88954c8057574e8257a7dc92301cbe48", + "title": "Granulocyte macrophage\u2010colony stimulating factor stimulates + both association and activation of phosphoinositide 3OH\u2010kinase and src\u2010related + tyrosine kinase(s) in human myeloid derived cells.", "abstract": "The signalling + pathways used by the GM\u2010CSF receptor are currently unknown. Here we show + that in human myeloid derived cells GM\u2010CSF can stimulate; (i) the accumulation + of PtdIns(3,4,5)P3; (ii) increases in p53/p56lyn and p62c\u2010yes directed + protein tyrosine kinase activities in anti\u2010lyn and anti\u2010c\u2010yes + antibody directed immunoprecipitates, respectively and; (iii) increases in + phosphoinositide 3OH\u2010kinase activity in antiphosphotyrosine, anti\u2010p53/p56lyn + and anti\u2010p62c\u2010yes antibody directed immunoprecipitates. These results + suggest that GM\u2010CSF can stimulate formation of protein tyrosine kinase + co\u2010ordinated signalling complexes, that contain p53/p56lyn, p62c\u2010yes + and an activated PtdInsP2 directed phosphoinositide 3OH\u2010kinase, which + can drive the accumulation of the putative second\u2010messenger PtdIns(3,4,5)P3.", + "venue": "EMBO Journal", "year": 1993, "referenceCount": 0, "citationCount": + 199, "influentialCitationCount": 5, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc413516?pdf=render", "status": null}, + "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1993-07-01", "journal": {"volume": "12", "name": "The + EMBO Journal"}, "authors": [{"authorId": "123396642", "name": "S. Corey"}, + {"authorId": "6757707", "name": "A. Eguinoa"}, {"authorId": "1436343879", + "name": "K. Puyana-Theall"}, {"authorId": "3713834", "name": "J. Bolen"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3345125", "name": + "F. Mollinedo"}, {"authorId": "2098983", "name": "T. Jackson"}, {"authorId": + "2869869", "name": "P. Hawkins"}, {"authorId": "2074217", "name": "L. Stephens"}]}, + {"paperId": "c06a10f95cd7b8fa831630247dc9b037691247ae", "externalIds": {"MAG": + "2159103585", "DOI": "10.1128/mcb.13.12.7708-7717.1993", "CorpusId": 46413261, + "PubMed": "8246987"}, "corpusId": 46413261, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/c06a10f95cd7b8fa831630247dc9b037691247ae", + "title": "Phosphatidylinositol (PI) 3-kinase and PI 4-kinase binding to the + CD4-p56lck complex: the p56lck SH3 domain binds to PI 3-kinase but not PI + 4-kinase", "abstract": "CD4 serves as a receptor for major histocompatibility + complex class II antigens and as a receptor for the human immunodeficiency + virus type 1 (HIV-1) viral coat protein gp120. It is coupled to the protein-tyrosine + kinase p56lck, an interaction necessary for an optimal response of certain + T cells to antigen. In addition to the protein-tyrosine kinase domain, p56lck + possesses Src homology 2 and 3 (SH2 and SH3) domains as well as a unique N-terminal + region. The mechanism by which p56lck generates intracellular signals is unclear, + although it has the potential to interact with various downstream molecules. + One such downstream target is the lipid kinase phosphatidylinositol 3-kinase + (PI 3-kinase), which has been found to bind to activated pp60src and receptor-tyrosine + kinases. In this study, we verified that PI 3-kinase associates with the CD4:p56lck + complex as judged by the presence of PI 3-phosphate generated from anti-CD4 + immunoprecipitates and detected by high-pressure liquid chromatographic analysis. + However, surprisingly, CD4-p56lck was also found to associate with another + lipid kinase, phosphatidylinositol 4-kinase (PI 4-kinase). The level of associated + PI 4-kinase was generally higher than PI 3-kinase activity. HIV-1 gp120 and + antibody-mediated cross-linking induced a 5- to 10-fold increase in the level + of CD4-associated PI 4- and PI 3-kinases. The use of glutathione S-transferase + fusion proteins carrying Lck-SH2, Lck-SH3, and Lck-SH2/SH3 domains showed + PI 3-kinase binding to the SH3 domain of p56lck, an interaction facilitated + by the presence of an adjacent SH2 domain. PI 4-kinase bound to neither the + SH2 nor the SH3 domain of p56lck. CD4-p56lck contributes PI 3- and PI 4-kinase + to the activation process of T cells and may play a role in HIV-1-induced + immune defects.", "venue": "Molecular and Cellular Biology", "year": 1993, + "referenceCount": 99, "citationCount": 149, "influentialCitationCount": 5, + "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc364842?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1993-12-01", "journal": {"volume": "13", "pages": "7708 + - 7717", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "49084493", "name": "K. Prasad"}, {"authorId": "2028875", "name": "R. Kapeller"}, + {"authorId": "2694949", "name": "O. Janssen"}, {"authorId": "5014538", "name": + "H. Repke"}, {"authorId": "1400208976", "name": "J. Duke-Cohan"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3745275", "name": "C. Rudd"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '253749' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:54 GMT + Via: + - 1.1 2199b1b2895d8f15e09ac5a5c5b50dbc.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - Ql1kZfwFd4eSkwYY2z-B7pRSXNOcWTuQ3izGPFHCabOlxrz5EWSGJA== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOcJHAtvHcFR3Q= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '253749' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:54 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - ef772cf2-f088-416d-b514-b93a0de8a320 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=800&limit=100 + response: + body: + string: '{"offset": 800, "next": 900, "data": [{"paperId": "d12468292ebd04c5fe35580632c7d027b1e2282f", + "externalIds": {"MAG": "2230463915", "DOI": "10.1016/B978-0-12-185285-6.50004-X", + "CorpusId": 180661452}, "corpusId": 180661452, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/d12468292ebd04c5fe35580632c7d027b1e2282f", + "title": "Contributors to Volume 18", "abstract": null, "venue": "", "year": + 1993, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["History"], + "s2FieldsOfStudy": [{"category": "History", "source": "external"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "18", "name": "Methods + in Neurosciences"}, "authors": [{"authorId": "3862153", "name": "J. Anthes"}, + {"authorId": "4892620", "name": "E. S. Bardes"}, {"authorId": "145671938", + "name": "R. Bell"}, {"authorId": "47217081", "name": "M. Billah"}, {"authorId": + "87501526", "name": "J. Bloomenthal"}, {"authorId": "8002063", "name": "R. + Borchardt"}, {"authorId": "3624038", "name": "U. Brodbeck"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "7626687", "name": "V. Chalifa"}, + {"authorId": "2095803270", "name": "R. A. Challiss"}, {"authorId": "6623565", + "name": "E. Claro"}, {"authorId": "6239175", "name": "M. Danin"}, {"authorId": + "2034026833", "name": "J. F. Dixon"}, {"authorId": "2362462", "name": "J. + Eichberg"}, {"authorId": "4851890", "name": "C. Erneux"}, {"authorId": "5565994", + "name": "J. Fain"}, {"authorId": "2875568", "name": "D. Frith"}, {"authorId": + "87387818", "name": "A. Ghalayini"}, {"authorId": "2056755217", "name": "Akio + Yamakawa"}]}, {"paperId": "d76fe36c4f18641cccfacd9e6e47166cece7e0fe", "externalIds": + {"MAG": "2099661341", "DOI": "10.1016/s0021-9258(18)98375-4", "CorpusId": + 28533702, "PubMed": "7683653"}, "corpusId": 28533702, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/d76fe36c4f18641cccfacd9e6e47166cece7e0fe", + "title": "Phosphoinositide 3-kinase is activated by phosphopeptides that bind + to the SH2 domains of the 85-kDa subunit.", "abstract": null, "venue": "Journal + of Biological Chemistry", "year": 1993, "referenceCount": 2, "citationCount": + 363, "influentialCitationCount": 15, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1993-05-05", "journal": {"volume": "268 13", "pages": "\n 9478-83\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "2972505", + "name": "C. Carpenter"}, {"authorId": "6603909", "name": "K. Auger"}, {"authorId": + "16077842", "name": "M. Chanudhuri"}, {"authorId": "8945145", "name": "M. + Yoakim"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": + "4790900", "name": "S. Shoelson"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "e93e986c1dcf13a1e854abfd710fb6074b7e0e07", "externalIds": {"MAG": + "2001467625", "DOI": "10.1126/SCIENCE.8235613", "CorpusId": 11509557, "PubMed": + "8235613"}, "corpusId": 11509557, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/e93e986c1dcf13a1e854abfd710fb6074b7e0e07", + "title": "Interaction of Shc with the zeta chain of the T cell receptor upon + T cell activation.", "abstract": "The shc oncogene product is tyrosine-phosphorylated + by Src family kinases and after its phosphorylation interacts with the adapter + protein Grb2 (growth factor receptor-bound protein 2). In turn, Grb2 interacts + with the guanine nucleotide exchange factor for Ras, mSOS. Because several + Src family kinases participate in T cell activation and Shc functions upstream + of Ras, the role of Shc in T cell signaling was examined. Shc was phosphorylated + on tyrosine after activation through the T cell receptor (TCR), and subsequently + interacted with Grb2 and mSOS. The Src homology region 2 (SH2) domain of Shc + directly interacted with the tyrosine-phosphorylated zeta chain of the TCR. + Thus, Shc may couple TCR activation to the Ras signaling pathway.", "venue": + "Science", "year": 1993, "referenceCount": 42, "citationCount": 315, "influentialCitationCount": + 14, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1993-11-05", "journal": {"volume": "262 5135", "pages": "\n 902-5\n ", + "name": "Science"}, "authors": [{"authorId": "144044294", "name": "K. Ravichandran"}, + {"authorId": "1414648502", "name": "K. K. Lee"}, {"authorId": "6731027", "name": + "Z. Songyang"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "145340757", "name": "P. Burn"}, {"authorId": "2549319", "name": "S. Burakoff"}]}, + {"paperId": "f50f7dd9de1beb834afbba500b015d2d986951b1", "externalIds": {"MAG": + "2746189979", "DOI": "10.1016/B978-0-12-185285-6.50018-X", "CorpusId": 90330609}, + "corpusId": 90330609, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/f50f7dd9de1beb834afbba500b015d2d986951b1", + "title": "[12] - Phosphatidylinositol 3-Kinase", "abstract": null, "venue": + "", "year": 1993, "referenceCount": 15, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], + "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "18", "name": "Methods + in Neurosciences"}, "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, + {"authorId": "2112191705", "name": "D. Kaplan"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "f8ad1671ef033b73f5a9ed3d155bfc710df1ad72", "externalIds": + {"MAG": "2150627341", "DOI": "10.1128/mcb.13.10.6052-6063.1993", "CorpusId": + 40060759, "PubMed": "8413207"}, "corpusId": 40060759, "publicationVenue": + {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", "name": "Molecular and Cellular + Biology", "type": "journal", "alternate_names": ["Mol Cell Biology"], "issn": + "0270-7306", "url": "https://mcb.asm.org/", "alternate_urls": ["http://mcb.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/f8ad1671ef033b73f5a9ed3d155bfc710df1ad72", + "title": "Internalization of activated platelet-derived growth factor receptor-phosphatidylinositol-3'' + kinase complexes: potential interactions with the microtubule cytoskeleton", + "abstract": "Phosphatidylinositol (PI)-3'' kinase catalyzes the formation + of PI 3,4-diphosphate and PI 3,4,5-triphosphate in response to stimulation + of cells by platelet-derived growth factor (PDGF). Here we report that tyrosine-phosphorylated + PDGF receptors, the p85 subunit of PI-3'' kinase (p85), and activated PI-3'' + kinase are found in isolated clathrin-coated vesicles within 2 min of exposure + of cells to PDGF, indicating that both receptor and activated PI-3'' kinase + enter the endocytic pathway. Immunofluorescence analysis of p85 in serum-starved + cells revealed a punctate/reticular staining pattern, concentrated in the + perinuclear region and displaying high focal concentration at the centrosome. + In addition, partial coalignment of p85 with microtubules was observed after + optical sectioning microscopy and image reconstruction. The association of + p85 with the microtubule network was further evidenced by the microtubule-depolymerizing + drug nocodazole, which caused a redistribution of p85 from the perinuclear + region to the cell periphery. Interestingly, the most significant effect of + PDGF on the distribution of p85 was an increase in the staining intensity + of this protein in the perinuclear region, and this effect was eliminated + by prior treatment of cells with nocodazole. These results suggest that PDGF + receptor-p85 complexes internalize and transit in association with the microtubule + cytoskeleton. In addition, the high concentration of p85 in intracellular + structures in the absence of PDGF stimulation suggests additional roles for + this protein independent of its association with receptor tyrosine kinases.", + "venue": "Molecular and Cellular Biology", "year": 1993, "referenceCount": + 36, "citationCount": 164, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://mcb.asm.org/content/13/10/6052.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1993-10-01", "journal": {"volume": + "13", "pages": "6052 - 6063", "name": "Molecular and Cellular Biology"}, "authors": + [{"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": "4151645", "name": + "R. Chakrabarti"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "4742824", "name": "F. Fay"}, {"authorId": "3950323", "name": "S. Corvera"}]}, + {"paperId": "4fd524fb1e296516a35d1db366f8a441841765f2", "externalIds": {"MAG": + "1510919372", "DOI": "10.1016/s0021-9258(18)41950-3", "CorpusId": 21163314, + "PubMed": "1380963"}, "corpusId": 21163314, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/4fd524fb1e296516a35d1db366f8a441841765f2", + "title": "Nerve growth factor promotes the activation of phosphatidylinositol + 3-kinase and its association with the trk tyrosine kinase.", "abstract": null, + "venue": "Journal of Biological Chemistry", "year": 1992, "referenceCount": + 0, "citationCount": 229, "influentialCitationCount": 7, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1992-08-25", "journal": {"volume": "267 24", "pages": "\n 17472-7\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "4324390", + "name": "S. Soltoff"}, {"authorId": "144521093", "name": "S. Rabin"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "32389352", "name": "D. Kaplan"}]}, + {"paperId": "8a7a157ffede70d7a241ad8e3d7cbbb4f8b3c76e", "externalIds": {"MAG": + "2239405256", "DOI": "10.1042/BJ2840039", "CorpusId": 37882114, "PubMed": + "1318025"}, "corpusId": 37882114, "publicationVenue": {"id": "64838252-a209-4424-a778-3b86b4a83c48", + "name": "Biochemical Journal", "type": "journal", "alternate_names": ["Biochem + J"], "issn": "0264-6021", "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, + "url": "https://www.semanticscholar.org/paper/8a7a157ffede70d7a241ad8e3d7cbbb4f8b3c76e", + "title": "Purification and characterization of human erythrocyte phosphatidylinositol + 4-kinase. Phosphatidylinositol 4-kinase and phosphatidylinositol 3-monophosphate + 4-kinase are distinct enzymes.", "abstract": "PtdIns 4-kinase has been purified + 83,000-fold from human erythrocyte membranes. The major protein detected by + SDS/PAGE is of molecular mass 56 kDa, and enzymic activity can be renatured + from this band of the gel. The characteristics of this enzyme are similar + to other type II PtdIns kinases previously described: PtdIns presented in + Triton X-100 micelles is preferred as a substrate over PtdIns vesicles, the + enzyme possesses a relatively low Km for ATP (20 microM), and adenosine is + an effective inhibitor. A monoclonal antibody raised against bovine brain + type II PtdIns 4-kinase is an effective inhibitor of the purified enzyme. + PtdIns(4,5)P2 inhibits by approx. 50% when added in equimolar amounts with + PtdIns; PtdIns4P has little effect on activity. A PtdIns3P 4-kinase activity + has also been detected in erythrocyte lysates. Approximately two-thirds of + this activity is in the cytosolic fraction and one-third in the membrane fraction. + No PtdIns3P 4-kinase activity could be detected in the purified type II PtdIns + 4-kinase preparation, nor could this activity be detected in a bovine brain + type III PtdIns 4-kinase preparation. The monoclonal antibody that inhibits + the type II PtdIns 4-kinase does not affect the PtdIns3P 4-kinase activity + in the membrane fraction. The cytosolic PtdIns3P 4-kinase can be efficiently + recovered from a 60%-satd.-(NH4)2SO4 precipitate that is virtually free of + PtdIns 4-kinase activity. We conclude that PtdIns3P 4-kinase is a new enzyme + distinct from previously characterized PtdIns 4-kinases, and that this enzyme + prefers PtdIns3P over PtdIns as a substrate.", "venue": "Biochemical Journal", + "year": 1992, "referenceCount": 0, "citationCount": 33, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1132694?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1992-05-15", "journal": {"volume": "284 ( Pt 1)", "pages": + "\n 39-45\n ", "name": "The Biochemical journal"}, "authors": + [{"authorId": "144157656", "name": "A. Graziani"}, {"authorId": "50678030", + "name": "L. Ling"}, {"authorId": "10330714", "name": "G. Endemann"}, {"authorId": + "2972505", "name": "C. Carpenter"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "ab4903ec94fab162c3af60a5eccfb42c72512397", "externalIds": {"MAG": + "1995503266", "DOI": "10.1101/SQB.1992.057.01.010", "CorpusId": 44794812, + "PubMed": "1339706"}, "corpusId": 44794812, "publicationVenue": {"id": "e24353f5-13a9-4d82-8e33-329cd22634a0", + "name": "Cold Spring Harbor Symposia on Quantitative Biology", "type": "journal", + "alternate_names": ["Cold Spring Harb Symp Quant Biology"], "issn": "0091-7451", + "url": "https://www.cshlpress.com/", "alternate_urls": ["http://symposium.cshlp.org/content/by/year", + "http://symposium.cshlp.org/", "http://symposium.cshlp.org/site/misc/index_archive.xhtml"]}, + "url": "https://www.semanticscholar.org/paper/ab4903ec94fab162c3af60a5eccfb42c72512397", + "title": "Phosphatidylinositol-3 kinase and growth regulation.", "abstract": + null, "venue": "Cold Spring Harbor Symposia on Quantitative Biology", "year": + 1992, "referenceCount": 0, "citationCount": 26, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + null, "journal": {"volume": "57", "pages": "\n 75-80\n ", + "name": "Cold Spring Harbor symposia on quantitative biology"}, "authors": + [{"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "2972505", "name": + "C. Carpenter"}, {"authorId": "6603909", "name": "K. Auger"}, {"authorId": + "2028875", "name": "R. Kapeller"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "dc2a65a49dba5ef71f34ab196d06173f85e595fc", + "externalIds": {"MAG": "1636397264", "DOI": "10.1016/S0021-9258(18)41922-9", + "CorpusId": 28992858, "PubMed": "1324928"}, "corpusId": 28992858, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/dc2a65a49dba5ef71f34ab196d06173f85e595fc", + "title": "Ouabain-resistant transfectants of the murine ouabain resistance + gene contain mutations in the alpha-subunit of the Na,K-ATPase.", "abstract": + null, "venue": "Journal of Biological Chemistry", "year": 1992, "referenceCount": + 0, "citationCount": 16, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle", "Study"], "publicationDate": "1992-08-25", "journal": {"volume": + "267 24", "pages": "\n 17271-8\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "5601835", "name": "L. Cantley"}, + {"authorId": "48666973", "name": "X. M. Zhou"}, {"authorId": "2056117768", + "name": "M. J. Cunha"}, {"authorId": "48381149", "name": "J. Epstein"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "dde614da0efd54672d584a131a275d905ed65514", + "externalIds": {"MAG": "1583451712", "DOI": "10.1128/jvi.66.3.1702-1708.1992", + "CorpusId": 25071119, "PubMed": "1371171"}, "corpusId": 25071119, "publicationVenue": + {"id": "dd4e1ddc-2cf4-4384-9544-cc9a88639c1e", "name": "Journal of Virology", + "type": "journal", "alternate_names": ["J Virol"], "issn": "0022-538X", "url": + "https://jvi.asm.org/", "alternate_urls": ["http://jvi.asm.org/"]}, "url": + "https://www.semanticscholar.org/paper/dde614da0efd54672d584a131a275d905ed65514", + "title": "Transformation-defective mutants of polyomavirus middle T antigen + associate with phosphatidylinositol 3-kinase (PI 3-kinase) but are unable + to maintain wild-type levels of PI 3-kinase products in intact cells", "abstract": + "Middle T antigen (MT) of polyomavirus causes transformation by associating + with a number of cellular proteins. The association with and activation of + two such proteins, phosphatidylinositol 3-kinase (PI 3-kinase) and pp60c-src, + appears to be necessary for transformation by MT. The tyrosine kinase activity + of MT-associated pp60c-src is significantly increased when assayed in vitro, + and levels of phosphotyrosine-containing proteins are elevated in vivo. Similarly, + levels of the PI 3-kinase products phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] + and phosphatiylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] are constitutively + elevated in MT-transformed cells. However, the formation of a complete MT/cellular + protein complex and the activation of tyrosine kinase are not sufficient to + cause transformation, since the transformation-defective mutants 248m and + dl1015 associate with all wild-type MT-associated proteins, including PI 3-kinase + and pp60c-src, and neither mutant appears to be defective in MT-associated + tyrosine kinase activity. Studies presented here compared (i) the amount of + PI 3-kinase activity associated with the MT complex and (ii) levels of [3H]inositol + incorporation into PI 3-kinase products in cells expressing mutant or wild-type + MT. The results show that dl1015 is defective in both assays, whereas 248m + is defective only for incorporation of [3H]inositol into PI(3,4,5)P2 and PI(3,4)P3. + These findings identify a biochemical defect in the 248m mutant and corroborate + previous results correlating transformation and elevated levels of PI 3-kinase + products in vivo. In addition, they indicate that PI 3-kinase product levels + are affected by factors other than simply the amount of PI 3-kinase activity + associated with the MT complex.", "venue": "Journal of Virology", "year": + 1992, "referenceCount": 38, "citationCount": 61, "influentialCitationCount": + 0, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc240916?pdf=render", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1992-03-01", "journal": {"volume": + "66", "pages": "1702 - 1708", "name": "Journal of Virology"}, "authors": [{"authorId": + "50678030", "name": "L. Ling"}, {"authorId": "144082761", "name": "B. Druker"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6665338", "name": + "T. Roberts"}]}, {"paperId": "e8d899326c33bee7d4e0ec59850f377a4860a152", "externalIds": + {"MAG": "2489175956", "DOI": "10.1016/B978-0-12-150403-8.50010-5", "CorpusId": + 88887564}, "corpusId": 88887564, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/e8d899326c33bee7d4e0ec59850f377a4860a152", + "title": "Phosphatidylinositol 3-kinase: A Novel Signal Transduction Pathway?", + "abstract": null, "venue": "", "year": 1992, "referenceCount": 69, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": "Biology", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "pages": "175-194", "name": ""}, "authors": [{"authorId": "6603909", "name": + "K. Auger"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "f3c3b7116399fd5c74c2000f34e929b605a28f38", "externalIds": {"MAG": "1523963819", + "DOI": "10.1016/s0021-9258(18)42781-0", "CorpusId": 22931330, "PubMed": "1372000"}, + "corpusId": 22931330, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/f3c3b7116399fd5c74c2000f34e929b605a28f38", + "title": "Polyoma virus middle T antigen-pp60c-src complex associates with + purified phosphatidylinositol 3-kinase in vitro.", "abstract": null, "venue": + "Journal of Biological Chemistry", "year": 1992, "referenceCount": 0, "citationCount": + 57, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Computer + Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1992-03-15", "journal": {"volume": "267 8", + "pages": "\n 5408-15\n ", "name": "The Journal of biological + chemistry"}, "authors": [{"authorId": "6603909", "name": "K. Auger"}, {"authorId": + "2972505", "name": "C. Carpenter"}, {"authorId": "4790900", "name": "S. Shoelson"}, + {"authorId": "1400810799", "name": "H. Piwnica-Worms"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "4fd0a6c8dbc88847feb927aef636bab44a758747", + "externalIds": {"MAG": "1575463095", "DOI": "10.1016/s0021-9258(18)98660-6", + "CorpusId": 19790894, "PubMed": "1713578"}, "corpusId": 19790894, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/4fd0a6c8dbc88847feb927aef636bab44a758747", + "title": "Interleukin-2 receptor regulates activation of phosphatidylinositol + 3-kinase.", "abstract": null, "venue": "Journal of Biological Chemistry", + "year": 1991, "referenceCount": 2, "citationCount": 127, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1991-08-05", "journal": {"volume": "266 22", "pages": "\n 14167-70\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "3019702", + "name": "B. Remillard"}, {"authorId": "145207655", "name": "R. Petrillo"}, + {"authorId": "36026052", "name": "W. Maslinski"}, {"authorId": "4103053", + "name": "M. Tsudo"}, {"authorId": "48909349", "name": "T. Strom"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "10119277", "name": "L. Varticovski"}]}, + {"paperId": "57879f64de3c2012755817e78ee4fb45aaa43d38", "externalIds": {"MAG": + "2416916901", "CorpusId": 39692600, "PubMed": "1654970"}, "corpusId": 39692600, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/57879f64de3c2012755817e78ee4fb45aaa43d38", + "title": "Novel polyphosphoinositides in cell growth and activation.", "abstract": + "The \"conventional\" polyphosphoinositide pathway is important for the transmission + and amplification of signals across the cell membrane. Ligand-induced activation + of phospholipase C results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate + to produce the well-characterized second messengers, inositol 1,4,5-trisphosphate + and diacylglycerol. Recently, three novel polyphosphoinositides have been + implicated as important signaling molecules for cell proliferation and activation. + These lipids are phosphorylated in the D-3 position of the inositol ring and + appear to represent branch points from the conventional polyphosphoinositide + pathway.", "venue": "Cancer cells", "year": 1991, "referenceCount": 0, "citationCount": + 55, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": "1991-07-01", "journal": {"volume": "3 7", "pages": "\n 263-70\n ", + "name": "Cancer cells"}, "authors": [{"authorId": "6603909", "name": "K. Auger"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "60f95b0b5d65105d67f7c270708210549487aa72", + "externalIds": {"MAG": "1611606593", "DOI": "10.1016/s0021-9258(18)98918-0", + "CorpusId": 35657125, "PubMed": "2061319"}, "corpusId": 35657125, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/60f95b0b5d65105d67f7c270708210549487aa72", + "title": "Rapid release of bound glucose-6-phosphate dehydrogenase by growth + factors. Correlation with increased enzymatic activity.", "abstract": null, + "venue": "Journal of Biological Chemistry", "year": 1991, "referenceCount": + 1, "citationCount": 113, "influentialCitationCount": 3, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1991-07-05", "journal": {"volume": + "266 19", "pages": "\n 12442-8\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "32835609", "name": "R. Stanton"}, + {"authorId": "40618752", "name": "J. Seifter"}, {"authorId": "2076977850", + "name": "D. Boxer"}, {"authorId": "49086039", "name": "E. Zimmerman"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "673c3b345ddecddcfb1fbee37573235ae330f91d", + "externalIds": {"MAG": "2402463253", "DOI": "10.1042/BJ2730063", "CorpusId": + 21859781, "PubMed": "1846531"}, "corpusId": 21859781, "publicationVenue": + {"id": "64838252-a209-4424-a778-3b86b4a83c48", "name": "Biochemical Journal", + "type": "journal", "alternate_names": ["Biochem J"], "issn": "0264-6021", + "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, "url": + "https://www.semanticscholar.org/paper/673c3b345ddecddcfb1fbee37573235ae330f91d", + "title": "A monoclonal antibody distinguishes two types of phosphatidylinositol + 4-kinase.", "abstract": "A monoclonal antibody has been developed against + the type II PtdIns 4-kinase from bovine brain. This antibody, 4C5G, causes + greater than 90% inhibition of the type II PtdIns 4-kinase from bovine brain, + rat brain and human erythrocytes. However, it fails to inhibit type III PtdIns + 4-kinase from bovine brain or PtdIns 3-kinase from rat liver. These results + suggest that type II and type III PtdIns 4-kinases are distinct gene products, + and that 4C5G will be useful in studying the function of the type II PtdIns + 4-kinase.", "venue": "Biochemical Journal", "year": 1991, "referenceCount": + 0, "citationCount": 45, "influentialCitationCount": 3, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc1149879?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": null, "journal": {"volume": "273(Pt + 1)", "pages": "\n 63-6\n ", "name": "The Biochemical journal"}, + "authors": [{"authorId": "10330714", "name": "G. Endemann"}, {"authorId": + "144157656", "name": "A. Graziani"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "6a61c204d7bfb6d6afd0abec49c344f468f65fee", "externalIds": {"MAG": + "1915712652", "DOI": "10.1128/mcb.11.2.1107-1113.1991", "CorpusId": 26203872, + "PubMed": "1846663"}, "corpusId": 26203872, "publicationVenue": {"id": "7b32fa10-02cb-49a7-a303-15aa60030b9b", + "name": "Molecular and Cellular Biology", "type": "journal", "alternate_names": + ["Mol Cell Biology"], "issn": "0270-7306", "url": "https://mcb.asm.org/", + "alternate_urls": ["http://mcb.asm.org/"]}, "url": "https://www.semanticscholar.org/paper/6a61c204d7bfb6d6afd0abec49c344f468f65fee", + "title": "Activation of phosphatidylinositol 3-kinase in cells expressing + abl oncogene variants", "abstract": "A phosphoinositide kinase specific for + the D-3 position of the inositol ring, phosphatidylinositol (PI) 3-kinase, + associates with activated receptors for platelet-derived growth factor, insulin, + and colony-stimulating factor 1, with products of the oncogenes src, fms, + yes, crk, and with polyomavirus middle T antigen. Efficient fibroblast transformation + by proteins of the abl and src oncogene families requires activation of their + protein-tyrosine kinase activity and membrane association via an amino-terminal + myristoylation. We have demonstrated that the PI 3-kinase directly associates + with autophosphorylated, activated protein-tyrosine kinase variants of the + abl protein. In vivo, this association leads to accumulation of the highly + phosphorylated products of PI 3-kinase, PI-3,4-bisphosphate and PI-3,4,5-trisphosphate, + only in myristoylated, transforming abl protein variants. Myristoylation thus + appears to be required to recruit PI 3-kinase activity to the plasma membrane + for in vivo activation and correlates with the mitogenicity of the abl protein + variants.", "venue": "Molecular and Cellular Biology", "year": 1991, "referenceCount": + 45, "citationCount": 202, "influentialCitationCount": 8, "isOpenAccess": true, + "openAccessPdf": {"url": "https://authors.library.caltech.edu/30211/1/VARmcb91.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1991-02-01", "journal": {"volume": "11", "pages": "1107 + - 1113", "name": "Molecular and Cellular Biology"}, "authors": [{"authorId": + "10119277", "name": "L. Varticovski"}, {"authorId": "2028224", "name": "G. + Daley"}, {"authorId": "144760257", "name": "P. Jackson"}, {"authorId": "144293138", + "name": "D. Baltimore"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "857f20edc21622440f3f7877a6b738756024da92", "externalIds": {"MAG": + "2462398491", "DOI": "10.1016/s0021-9258(18)54536-1", "CorpusId": 23591831, + "PubMed": "1718989"}, "corpusId": 23591831, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/857f20edc21622440f3f7877a6b738756024da92", + "title": "The tyrosine-phosphorylated hepatocyte growth factor/scatter factor + receptor associates with phosphatidylinositol 3-kinase.", "abstract": null, + "venue": "Journal of Biological Chemistry", "year": 1991, "referenceCount": + 0, "citationCount": 227, "influentialCitationCount": 1, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1991-11-25", "journal": {"volume": "266 33", "pages": + "\n 22087-90\n ", "name": "The Journal of biological chemistry"}, + "authors": [{"authorId": "144157656", "name": "A. Graziani"}, {"authorId": + "8927126", "name": "D. Gramaglia"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4896953", "name": "P. Comoglio"}]}, {"paperId": "984e255eda45d9904e6b42789cd523b1c626b39d", + "externalIds": {"MAG": "2022163051", "DOI": "10.1210/MEND-5-6-769", "CorpusId": + 2437375, "PubMed": "1656240"}, "corpusId": 2437375, "publicationVenue": {"id": + "828763fb-d162-432e-929f-4841dc01a887", "name": "Molecular Endocrinology", + "type": "journal", "alternate_names": ["Mol Endocrinol"], "issn": "0888-8809", + "url": "http://mend.endojournals.org/"}, "url": "https://www.semanticscholar.org/paper/984e255eda45d9904e6b42789cd523b1c626b39d", + "title": "Mutations in the juxtamembrane region of the insulin receptor impair + activation of phosphatidylinositol 3-kinase by insulin.", "abstract": "CHO/IRF960/T962 + cells express a mutant human insulin receptor in which Tyr960 and Ser962 in + the juxtamembrane region of the receptor''s beta-subunit are replaced by Phe + and Thr, respectively. The mutant insulin receptor undergoes autophosphorylation + normally in response to insulin; however, insulin fails to stimulate thymidine + incorporation into DNA, glycogen synthesis, and tyrosyl phosphorylation of + an endogenous substrate pp185 in these cells. Another putative substrate of + the insulin receptor tyrosine kinase is phosphatidylinositol 3-kinase (Ptdlns + 3-kinase). We have previously shown that Ptdlns 3-kinase activity in Chinese + hamster ovary cells expressing the wild-type human insulin receptor (CHO/IR) + increases in both antiphosphotyrosine [anti-Tyr(P)] immunoprecipitates and + intact cells in response to insulin. In the present study a new technique + (detection of the 85-kDa subunit of Ptdlns 3-kinase using [32P]phosphorylated + polyoma virus middle T-antigen as probe) is used to monitor the Ptdlns 3-kinase + protein. The 85-kDa subunit of Ptdlns 3-kinase is precipitated by anti-Tyr(P) + antibodies from insulin-stimulated CHO/IR cells, but markedly less protein + is precipitated from CHO/IRF960/T962 cells. The amount of Ptdlns 3-kinase + activity in the immunoprecipitates was also reduced in the CHO/IRF960/T962 + cells compared to CHO/IR cells. In intact CHO/IRF960/T962 cells, insulin failed + to stimulate phosphate incorporation into one of the products of activated + Ptdlns 3-kinase, phosphatidylinositol-3,4-bisphosphate [Ptdlns(3,4)P2], whereas + it caused a 12-fold increase in CHO/IR cells. In contrast, phosphate incorporation + into another product, phosphatidylinositol trisphosphate [PtdlnsP3], was only + partially depressed in the CHO/IRF960/T962 cells.(ABSTRACT TRUNCATED AT 250 + WORDS)", "venue": "Molecular Endocrinology", "year": 1991, "referenceCount": + 30, "citationCount": 36, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://academic.oup.com/mend/article-pdf/5/6/769/9078708/mend0769.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1991-06-01", "journal": {"volume": "5 6", "pages": + "\n 769-77\n ", "name": "Molecular endocrinology"}, "authors": + [{"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": "48543513", + "name": "K. Chen"}, {"authorId": "8945145", "name": "M. Yoakim"}, {"authorId": + "4362128", "name": "B. Schaffhausen"}, {"authorId": "35244019", "name": "J. + Backer"}, {"authorId": "2343034", "name": "M. White"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "3978573", "name": "N. Ruderman"}]}, {"paperId": + "a2df94baba49e0676f6bedb5531fcfa140ed7599", "externalIds": {"MAG": "2005529016", + "DOI": "10.1016/0092-8674(91)90639-G", "CorpusId": 10422282, "PubMed": "1846320"}, + "corpusId": 10422282, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/a2df94baba49e0676f6bedb5531fcfa140ed7599", + "title": "Oncogenes and signal transduction", "abstract": null, "venue": "Cell", + "year": 1991, "referenceCount": 219, "citationCount": 2473, "influentialCitationCount": + 51, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle", "Study"], + "publicationDate": "1991-01-25", "journal": {"volume": "64", "pages": "281-302", + "name": "Cell"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "6603909", "name": "K. Auger"}, {"authorId": "2972505", "name": + "C. Carpenter"}, {"authorId": "21162853", "name": "B. Duckworth"}, {"authorId": + "144157656", "name": "A. Graziani"}, {"authorId": "2028875", "name": "R. Kapeller"}, + {"authorId": "4324390", "name": "S. Soltoff"}]}, {"paperId": "dcc5d603c6ea216c148ed717982cbef2954599da", + "externalIds": {"MAG": "91266548", "DOI": "10.1016/0076-6879(91)98010-4", + "CorpusId": 29005038, "PubMed": "1649958"}, "corpusId": 29005038, "publicationVenue": + {"id": "1e7039c8-e30c-4af0-b7d3-f5e05dff5d21", "name": "Methods in Enzymology", + "type": "journal", "alternate_names": ["Method Enzymol"], "issn": "0076-6879", + "alternate_issns": ["1557-7988"], "url": "https://www.elsevier.com/books/book-series/methods-in-enzymology", + "alternate_urls": ["http://www.sciencedirect.com/science/bookseries/00766879"]}, + "url": "https://www.semanticscholar.org/paper/dcc5d603c6ea216c148ed717982cbef2954599da", + "title": "Identification and quantification of polyphosphoinositides produced + in response to platelet-derived growth factor stimulation.", "abstract": null, + "venue": "Methods in Enzymology", "year": 1991, "referenceCount": 21, "citationCount": + 139, "influentialCitationCount": 8, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": null, "journal": {"volume": "198", "pages": "\n 78-87\n ", + "name": "Methods in enzymology"}, "authors": [{"authorId": "5260667", "name": + "L. Serunian"}, {"authorId": "6603909", "name": "K. Auger"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "1b2744489cb1873f4cf96fe9a82081635ccbc8ab", + "externalIds": {"MAG": "2092045274", "DOI": "10.1073/PNAS.87.4.1411", "CorpusId": + 34520561, "PubMed": "2154747"}, "corpusId": 34520561, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/1b2744489cb1873f4cf96fe9a82081635ccbc8ab", + "title": "Activation of phosphatidylinositol 3-kinase by insulin.", "abstract": + "Insulin action appears to require the protein-tyrosine kinase domain of the + beta subunit of the insulin receptor. Despite this, the identities and biochemical + functions of the cellular targets of this tyrosine kinase are unknown. A phosphatidylinositol + 3-kinase (PI 3-kinase) that phosphorylates the D-3 position of the inositol + ring associates with several protein-tyrosine kinases. Here we report that + PI 3-kinase activity is immunoprecipitated from insulin-stimulated CHO cells + by antiphosphotyrosine and anti-insulin receptor antibodies. Insulin as low + as 0.3 nM increased immunoprecipitable PI 3-kinase activity within 1 min. + Increases in activity were much greater in CHO cells expressing the human + insulin receptor (100,000 receptors per cell) than in control CHO cells (2000 + receptors per cell). During insulin stimulation, various lipid products of + the PI 3-kinase either appeared or increased in quantity in intact cells, + suggesting that the appearance of immunoprecipitable PI 3-kinase reflects + an increase in its activity in vivo. These results indicate that insulin at + physiological concentrations regulates the PI 3-kinase and suggest that this + regulation involves a physical association between the insulin receptor and + the PI 3-kinase and tyrosyl phosphorylation.", "venue": "Proceedings of the + National Academy of Sciences of the United States of America", "year": 1990, + "referenceCount": 5, "citationCount": 451, "influentialCitationCount": 12, + "isOpenAccess": true, "openAccessPdf": {"url": "http://www.pnas.org/content/87/4/1411.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1990-02-01", "journal": {"volume": "87", "pages": "1411 + - 1415", "name": "Proceedings of the National Academy of Sciences of the United + States of America"}, "authors": [{"authorId": "3978573", "name": "N. Ruderman"}, + {"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": "2343034", "name": + "M. White"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "3a38cc52e2fbf9f5767e3983fa2443d69f07d5f7", "externalIds": {"MAG": "2185282572", + "CorpusId": 97883248}, "corpusId": 97883248, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/3a38cc52e2fbf9f5767e3983fa2443d69f07d5f7", + "title": "Comparison with the Muscarinic Agonist Carbachol", "abstract": "The + effects of extracellular ATP on ion fluxes and the intracellular free Ca 2\u00a7 + concentration ((Ca~+)i) were examined using a suspension of rat parotid acinar + cells and were contrasted with the effects of the muscarinic agonist carba- + chol. Although ATP and carbachol both rapidly increased (Ca2+) i about threefold + above the resting level (200-250 nM), the effect of ATP was due primarily + to an influx of Ca ~+ across the plasma membrane, while the initial response + to carbachol was due to a release of Ca ~\u00a7 from intracellular stores. + Within 10 s, ATP (1 mM) and carbachol (20 #M) reduced the cellular C1- content + by 39-50% and cell vol- ume by 15-25%. Both stimuli reduced the cytosolic + K + content by 57-65%, but there were marked differences in the rate and pattern + of net K \u00a7 movement as well as the effects of K + channel inhibitors + on the effluxes initiated by the two stimuli. The maximum rate of the ATP-stimulated + K \u00a7 efflux (~2,200 nmol K+/mg protein per min) was about two-thirds that + of the carbachol-initiated efflux rate, and was reduced by ~30% (vs. 60% for + the carbachol-stimulated K + efflux) by TEA (tetra- ethylammonium), an inhibitor + of the large conductance (BK) K \u00a7 channel. Charyb- dotoxin, another K + \u00a7 channel blocker, was markedly more effective than TEA on the effects + of both agonists, and reduced the rate of K \u00a7 effiux initiated by both + ATP and carbachol by ~80%. The removal of extracellular Ca ~\u00a7 reduced + the ATP- and the carbachol-stimulated rates of K + efflux by 55 and 17%, respectively. + The rate of K + effiux initiated by either agonist was reduced by 78-95% in + cells that were loaded with BAPTA to slow the elevation of (Ca2+)i. These + results indicated that ATP and carbachol stimulated the effiux of K + through + multiple types of K \u00a7 permeable channels, and demonstrated that the relative + proportion of efflux", "venue": "", "year": 1990, "referenceCount": 47, "citationCount": + 6, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "name": ""}, "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": + "144664118", "name": "M. McMillian"}, {"authorId": "5783113", "name": "E. + Cragoe"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3683975", + "name": "B. Talamo"}]}, {"paperId": "3fdd62cb9174c24c737e7ba46e72491588c54336", + "externalIds": {"PubMedCentral": "2216318", "MAG": "2171783790", "DOI": "10.1085/JGP.95.2.319", + "CorpusId": 13505799, "PubMed": "1689766"}, "corpusId": 13505799, "publicationVenue": + {"id": "eb5b7fda-8fd6-48a1-bfed-2aac4b99cbee", "name": "The Journal of General + Physiology", "type": "journal", "alternate_names": ["J Gen Physiol"], "issn": + "0022-1295", "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=484", + "alternate_urls": ["http://jgp.rupress.org/"]}, "url": "https://www.semanticscholar.org/paper/3fdd62cb9174c24c737e7ba46e72491588c54336", + "title": "Effects of extracellular ATP on ion transport systems and [Ca2+]i + in rat parotid acinar cells. Comparison with the muscarinic agonist carbachol", + "abstract": "The effects of extracellular ATP on ion fluxes and the intracellular + free Ca2+ concentration ([Ca2+]i) were examined using a suspension of rat + parotid acinar cells and were contrasted with the effects of the muscarinic + agonist carbachol. Although ATP and carbachol both rapidly increased [Ca2+]i + about threefold above the resting level (200-250 nM), the effect of ATP was + due primarily to an influx of Ca2+ across the plasma membrane, while the initial + response to carbachol was due to a release of Ca2+ from intracellular stores. + Within 10 s, ATP (1 mM) and carbachol (20 microM) reduced the cellular Cl- + content by 39-50% and cell volume by 15-25%. Both stimuli reduced the cytosolic + K+ content by 57-65%, but there were marked differences in the rate and pattern + of net K+ movement as well as the effects of K+ channel inhibitors on the + effluxes initiated by the two stimuli. The maximum rate of the ATP- stimulated + K+ efflux (approximately 2,200 nmol K+/mg protein per min) was about two-thirds + that of the carbachol-initiated efflux rate, and was reduced by approximately + 30% (vs. 60% for the carbachol-stimulated K+ efflux) by TEA (tetraethylammonium), + an inhibitor of the large conductance (BK) K+ channel. Charybdotoxin, another + K+ channel blocker, was markedly more effective than TEA on the effects of + both agonists, and reduced the rate of K+ efflux initiated by both ATP and + carbachol by approximately 80%. The removal of extracellular Ca2+ reduced + the ATP- and the carbachol-stimulated rates of K+ efflux by 55 and 17%, respectively. + The rate of K+ efflux initiated by either agonist was reduced by 78-95% in + cells that were loaded with BAPTA to slow the elevation of [Ca2+]i. These + results indicated that ATP and carbachol stimulated the efflux of K+ through + multiple types of K(+)-permeable channels, and demonstrated that the relative + proportion of efflux through the different pathways was different for the + two stimuli. ATP and carbachol also stimulated the rapid entry of Na+ into + the parotid cell, and elevated the intracellular Na+ content to 4.4 and 2.6 + times the normal level, respectively. The rate of Na+ entry through Na(+)- + K(+)-2Cl- cotransport and Na(+)-H+ exchange was similar whether stimulated + by ATP, carbachol, or ionomycin, and uptake through these two carrier-mediated + transporters accounted for 50% of the ATP-promoted Na+ influx. The remainder + may be due to a nonselective cation channel and an ATP-gated cation channel + that is also permeable to Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)", "venue": + "The Journal of General Physiology", "year": 1990, "referenceCount": 61, "citationCount": + 82, "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": + {"url": "https://rupress.org/jgp/article-pdf/95/2/319/1249408/319.pdf", "status": + null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle", + "Study"], "publicationDate": "1990-02-01", "journal": {"volume": "95", "pages": + "319 - 346", "name": "The Journal of General Physiology"}, "authors": [{"authorId": + "4324390", "name": "S. Soltoff"}, {"authorId": "144664118", "name": "M. McMillian"}, + {"authorId": "5783113", "name": "E. Cragoe"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "3683975", "name": "B. Talamo"}]}, {"paperId": + "4a945a71468432a8c691957d6518b571bb436e5f", "externalIds": {"MAG": "2915750128", + "CorpusId": 104472401}, "corpusId": 104472401, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/4a945a71468432a8c691957d6518b571bb436e5f", + "title": "Phosphatidylinositol 3 kinase is activated by insulin", "abstract": + null, "venue": "", "year": 1990, "referenceCount": 0, "citationCount": 10, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "1990-08-16", "journal": null, + "authors": [{"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": "3978573", + "name": "N. Ruderman"}, {"authorId": "2343034", "name": "M. White"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "4abf293420ac6fabe46bc886619bfdccfa99b60c", + "externalIds": {"MAG": "2021855501", "DOI": "10.1016/0955-2863(90)90054-O", + "CorpusId": 25103037, "PubMed": "15539189"}, "corpusId": 25103037, "publicationVenue": + {"id": "cff0222c-6e21-445c-881c-3c9da8b7c947", "name": "Journal of Nutritional + Biochemistry", "type": "journal", "alternate_names": ["J Nutr Biochem"], "issn": + "0955-2863", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/525013/description#description", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/09552863", + "http://www.journals.elsevier.com/the-journal-of-nutritional-biochemistry/", + "https://www.journals.elsevier.com/the-journal-of-nutritional-biochemistry/"]}, + "url": "https://www.semanticscholar.org/paper/4abf293420ac6fabe46bc886619bfdccfa99b60c", + "title": "1,25(OH)2D3 increases calcium and phosphatidylinositol metabolism + in differentiating cultured human keratinocytes.", "abstract": null, "venue": + "Journal of Nutritional Biochemistry", "year": 1990, "referenceCount": 23, + "citationCount": 52, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1990-02-01", "journal": {"volume": + "1 2", "pages": "\n 81-7\n ", "name": "The Journal of nutritional + biochemistry"}, "authors": [{"authorId": "144606947", "name": "J. MacLaughlin"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4873870", "name": + "M. Holick"}]}, {"paperId": "7dd7d4d8ea9f4ae216a0411393fac1a960fe2a98", "externalIds": + {"MAG": "2066874852", "DOI": "10.1111/j.1749-6632.1990.tb37663.x", "CorpusId": + 36146594, "PubMed": "1705402"}, "corpusId": 36146594, "publicationVenue": + {"id": "fa1f0815-0811-4291-b4fc-8230a6c9bf5b", "name": "Annals of the New + York Academy of Sciences", "type": "journal", "alternate_names": ["Ann n y + Acad Sci"], "issn": "0077-8923", "url": "http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1749-6632", + "alternate_urls": ["http://www.annalsnyas.org/", "http://www.nyas.org/publications/annals/default.aspx", + "https://onlinelibrary.wiley.com/journal/17496632"]}, "url": "https://www.semanticscholar.org/paper/7dd7d4d8ea9f4ae216a0411393fac1a960fe2a98", + "title": "Elevation of [Ca2+]i and the Activation of Ion Channels and Fluxes + by Extracellular ATP and Phospholipase C\u2010Linked Agonists in Rat Parotid + Acinar Cells", "abstract": "Extracellular ATP initiates a variety of changes + in the parotid acinar cell. The initial effect appears to be the entry of + Ca2+ (and perhaps Na+), and a series of ion transport events result from the + subsequent elevation of [Ca2+]i. Agonists of phospholipase C-linked receptors + elevate [Ca2+]i by a different pathway, involving the generation of inositol + polyphosphate compounds, but share in the subsequent initiation of the ion + transport events. Although the maintenance of the physiological changes may + depend on specific inositol polyphosphate intermediates, the critical initiating + factor is the elevation of [Ca2+]i. Fluid secretion by the parotid gland is + triggered by the action of neurotransmitters, which alter the membrane permeability + of the acinar cell. The similarities between the two receptor-mediated activation + pathways suggests that ATP may act as a neurotransmitter and play a role in + the control of fluid secretion. Basing our analysis on the purinoceptor characteristics + outlined by Gordon, we suggest that the parotid receptor belongs to the P2Z + class, which is highly sensitive to ATP4-. Basing his analysis on the earlier + report by Gallacher of the effects of ATP on mouse parotid cells, Gordon placed + the parotid purinoceptor in a different P2 subclass (P2Y). However, our findings + of an increased potency of ATP in the absence of Mg2+, as well as the potency + order of different nucleotides, indicate that the P2Z class is a more appropriate + category.", "venue": "Annals of the New York Academy of Sciences", "year": + 1990, "referenceCount": 34, "citationCount": 43, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "1990-12-01", "journal": {"volume": "603", "name": "Annals of the New York + Academy of Sciences"}, "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, + {"authorId": "144664118", "name": "M. McMillian"}, {"authorId": "144776879", + "name": "J. Lechleiter"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3683975", "name": "B. Talamo"}]}, {"paperId": "aa8f12da64f41d14a9519e92c549bceb06680fe9", + "externalIds": {"MAG": "2014852355", "DOI": "10.1111/j.1749-6632.1990.tb37700.x", + "CorpusId": 84482224}, "corpusId": 84482224, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/aa8f12da64f41d14a9519e92c549bceb06680fe9", + "title": "ATP Produces Two Cai Responses in Rat Parotid Cells", "abstract": + "Extracellular ATP increased intracellular calcium (Ca,) in a biphasic manner + in Fura2-loaded rat parotid acinar cells, with a small effect apparent between + 0.1 and 10 p M ATP and a much larger effect observed between 50 and 300 p + M ATP (in the absence of Mg\u2019+ with 1 mM Ca\u2019 \u2019 present). This + latter effect, which we previously described,\u2019 appears to be mediated + by a P,,-purinergic receptor; blockade by high Mg\u2019 \u2019 or Ca2 \u2019 + suggests that ATP4 is the actual agonist, and the selective P,z agonist 3\u2019-0-(4benzoyl)benz.oyl-ATP + (Bz-ATP) was about 30-fold more potent and 3-fold more efficacious than ATP + (these differences being due, at least in part, to covalent activation by + Bz-ATP). In contrast, the more sensitive ATP response was only slightly diminished + by elevated Mg2 \u2019 or Ca\u2019 \u2019( 10 mM) in the buffer (this difference + probably being due to increased degradation of ATP and/or production of ADP, + which blocked the ATP response). Bz-ATP was ineffective as an agonist on the + more sensitive response to ATP, but other P,-purinergic agonists showed a + similar potency series for both ATP responses in parotid cells: ATP > ATP-y-S + 2 2I-MeS-ATP > > ITP and AMPCPP. Thus, the more sensitive response, though + not mediated through a P22 receptor, is more similar to this response than + to P2,or P,,-purinergic responses. 4,4\u2018-Diisothiocyano-2,2\u2019-stilbene + disulfonate (DIDS) and reactive blue 2 (Cibacron blue) blocked the large ATP4 + effect on Ca, and also inhibited [\u2018*P]ATP binding to parotid cells under + conditions (phosphate-buffered saline with no added Mg\u201d or Ca2+) selective + for ATP4. Reactive blue 2 pretreatment blocked irreversible effects of DIDS + and Bz-ATP, presumably by blocking the P2, receptor and protecting it from + covalent inactivation or activation, respectively. In contrast to Ca, responses + to ATP4 , the more sensitive response to ATP was slightly potentiated by both + DIDS and reactive blue 2 (this difference probably being due to inhibition + of ATPases). Both P,-receptors on parotid cells may open Ca\u2019 \u2019 -permeable + channels, since both responses are largely dependent on extracellular calcium + and are quenched by extracellular Mn2 \u2019 , in contrast to muscarinic agonists + and substance P. A weak effect of ATP on phosphatidylinositol turnover and + Ca, mobilization was due to ATP4 , since this effect required high concentrations + of ATP, was mimicked by Bz-ATP, and was blocked by DIDS and MgZ \u2019 . The + more sensitive ATP response may be physiologically important, since parasympathetic + denervation produced a 3-fold increase in the maximal Ca, response to 3 p + M ATP, with no change in the ATP4 response or in maximal carbachol or substance + P responses.", "venue": "", "year": 1990, "referenceCount": 1, "citationCount": + 3, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "1990-12-01", "journal": {"volume": + "603", "name": "Annals of the New York Academy of Sciences"}, "authors": [{"authorId": + "144664118", "name": "M. McMillian"}, {"authorId": "4324390", "name": "S. + Soltoff"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "3683975", + "name": "B. Talamo"}]}, {"paperId": "b2838fdd768aa383ce1f7e345c8dc8826ac8f7ad", + "externalIds": {"MAG": "1545503281", "DOI": "10.1016/S0021-9258(17)45429-9", + "CorpusId": 20077714, "PubMed": "2174051"}, "corpusId": 20077714, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/b2838fdd768aa383ce1f7e345c8dc8826ac8f7ad", + "title": "Purification and characterization of phosphoinositide 3-kinase from + rat liver.", "abstract": null, "venue": "Journal of Biological Chemistry", + "year": 1990, "referenceCount": 35, "citationCount": 533, "influentialCitationCount": + 11, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1990-11-15", "journal": + {"volume": "265 32", "pages": "\n 19704-11\n ", "name": "The + Journal of biological chemistry"}, "authors": [{"authorId": "2972505", "name": + "C. Carpenter"}, {"authorId": "21162853", "name": "B. Duckworth"}, {"authorId": + "6603909", "name": "K. Auger"}, {"authorId": "2055611224", "name": "B. Cohen"}, + {"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "d7021ed3b8cb53a59fca98463dc80d948e864a7a", + "externalIds": {"MAG": "1617300304", "DOI": "10.1111/J.1749-6632.1990.TB37699.X", + "CorpusId": 83965272}, "corpusId": 83965272, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/d7021ed3b8cb53a59fca98463dc80d948e864a7a", + "title": "Extracellular ATP Gates a Ca2+\u2010Permeable Nonselective Cation + Channel in Rat Parotid Acinar Cells", "abstract": "We investigated the effect + of ATP4on 4sCa2+ entry into rat parotid acinar cells. The maximum ATP-stimulated + influx rate (6 nmol/mg/min, with a of 150 pM) was about 20 times the basal + rate. 3''-0-( 4-Benzoy1)benzoyl-ATP ( Bz-ATP) was 30 times more potent and + nearly twice as effective as ATP in stimulating Ca2+ influx. Other analogues + were much less effective than ATP. The order of effectiveness of nucleotide + analogues on 45Ca2+ entry was Bz-ATP > ATP > ATP-y-S > 2-methylthio-ATP > + a$-methylene ATP, ADP. The potency and effectiveness of ATP were increased + 2-3-fold in the absence of extracellular Na2+, which may compete with Ca2+ + for entry through an ATP-gated Na+and Ca*+-permeable channel. 4,4''Diisothiocyano-2,2''-stilbene + disulfonate (DIDS), which has two -NCS groups, at 100 pM completely blocked + the ATP-stimulated influx (EC,,, = 40 pM). 4-Acetamino4''-isothiocyanostilbene-2,2''-disulfonate + (SITs), which has one -NCS group, was about 50% as potent as DIDS. 4,4''-Dinitrostilbene-2,2''-disulfonate + (DNDS), which lacks -NCS groups, at 1 mM was ineffective, as was K+SCN-. Reactive + blue 2 (Cibacron Blue), a nonstilbene compound, also blocked 45Ca2+ entry + (EC,, = 50 FM). The effect of DIDS was irreversible, but the effect of reactive + blue 2 was reversible by washing the cells. Reactive blue 2, added before + DIDS, blocked the irreversible effect of DIDS. Our conclusions are as follows: + 1) ATP activates a nonselective cation channel. 2) Stilbene compounds with + -NCS groups covalently block the binding of ATP to its receptor. 3 ) Reactive + blue 2 binds noncovalently to prevent DIDS and ATP binding.", "venue": "", + "year": 1990, "referenceCount": 0, "citationCount": 2, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": "1990-12-01", + "journal": {"volume": "603", "name": "Annals of the New York Academy of Sciences"}, + "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "144664118", + "name": "M. McMillian"}, {"authorId": "3683975", "name": "B. Talamo"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "ecc6ad0cd6f5143b26a6388d6b0e2d2d2c6f526f", + "externalIds": {"DOI": "10.1021/bi00503a001", "CorpusId": 35406982, "PubMed": + "2176895"}, "corpusId": 35406982, "publicationVenue": {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", + "name": "Biochemistry", "type": "journal", "issn": "0006-2960", "alternate_issns": + ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", "alternate_urls": + ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/ecc6ad0cd6f5143b26a6388d6b0e2d2d2c6f526f", + "title": "Phosphoinositide kinases.", "abstract": null, "venue": "Biochemistry", + "year": 1990, "referenceCount": 0, "citationCount": 147, "influentialCitationCount": + 13, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": null, "journal": {"volume": "29 51", "pages": "\n 11147-56\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "2972505", "name": "C. Carpenter"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "ed04a19ea30e280224800323560c7f435fd3a8ce", + "externalIds": {"MAG": "2917446036", "CorpusId": 104420985}, "corpusId": 104420985, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/ed04a19ea30e280224800323560c7f435fd3a8ce", + "title": "Phosphatidylinositol pathways in growth and transformation", "abstract": + null, "venue": "", "year": 1990, "referenceCount": 0, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": "1990-02-15", "journal": {"volume": + "", "pages": "246", "name": ""}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "5260667", "name": "L. Serunian"}, {"authorId": + "6603909", "name": "K. Auger"}, {"authorId": "10119277", "name": "L. Varticovski"}, + {"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": "2972505", "name": + "C. Carpenter"}, {"authorId": "2056828167", "name": "B. Drucker"}, {"authorId": + "3978573", "name": "N. Ruderman"}, {"authorId": "2343034", "name": "M. White"}]}, + {"paperId": "f2db7bcf4b61271d8264c8580726e6ae9dfe6141", "externalIds": {"MAG": + "1595741577", "DOI": "10.1016/s0021-9258(18)45672-4", "CorpusId": 24034131, + "PubMed": "2176203"}, "corpusId": 24034131, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/f2db7bcf4b61271d8264c8580726e6ae9dfe6141", + "title": "A novel pathway for the formation of phosphatidylinositol 3,4-bisphosphate. + Phosphorylation of phosphatidylinositol 3-monophosphate by phosphatidylinositol-3-monophosphate + 4-kinase.", "abstract": null, "venue": "Journal of Biological Chemistry", + "year": 1990, "referenceCount": 0, "citationCount": 41, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}, {"category": "Physics", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1990-12-25", "journal": {"volume": "265 36", "pages": "\n 22086-9\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "2107575636", + "name": "K. Yamamoto"}, {"authorId": "144157656", "name": "A. Graziani"}, + {"authorId": "2972505", "name": "C. Carpenter"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "7004693", "name": "E. Lapetina"}]}, {"paperId": + "fe00566546f2876557cd00b0ac501bd3990ca98e", "externalIds": {"MAG": "1789958833", + "DOI": "10.1128/jvi.64.10.4718-4725.1990", "CorpusId": 33672361, "PubMed": + "2168961"}, "corpusId": 33672361, "publicationVenue": {"id": "dd4e1ddc-2cf4-4384-9544-cc9a88639c1e", + "name": "Journal of Virology", "type": "journal", "alternate_names": ["J Virol"], + "issn": "0022-538X", "url": "https://jvi.asm.org/", "alternate_urls": ["http://jvi.asm.org/"]}, + "url": "https://www.semanticscholar.org/paper/fe00566546f2876557cd00b0ac501bd3990ca98e", + "title": "Production of novel polyphosphoinositides in vivo is linked to cell + transformation by polyomavirus middle T antigen", "abstract": "Phosphatidylinositol + 3-kinase associates with the polyomavirus middle T antigen (PyMTAg)-pp60c-src + complex in polyomavirus-transformed cells. Here we show that anti-PyMTAg immunoprecipitates + from PyMTAg-transformed NIH 3T3 cells have lipid kinase activities that phosphorylate + phosphatidylinositol, phosphatidylinositol-4-bisphosphate, and phosphatidylinositol-4,5-bisphosphate + at the D-3 position of the inositol ring to produce three new polyphosphoinositides: + phosphatidylinositol-3-phosphate (PI-3-P), phosphatidylinositol-3,4-bisphosphate + (PI-3,4-P2), and phosphatidylinositol trisphosphate (PIP3), respectively. + PI-3-P was detected in intact parental and PyMTAg-transformed NIH 3T3 fibroblasts + at both low and high cell densities. However, parental NIH 3T3 fibroblasts + produced no detectable PI-3,4-P2 or PIP3 at high density. In contrast, growing, + subconfluent cells and wild-type PyMTAg-transformed cells at high density + had greatly enhanced incorporation of [3H]-inositol into these highly phosphorylated + lipids. Cells transfected with a transformation-defective mutant of PyMTAg + had undetectable levels of PI-3,4-P2 and PIP3 at high density. Thus, the synthesis + of novel polyphosphoinositides by lipid kinase activity associated with PyMTAg + correlates with cell growth and transformation.", "venue": "Journal of Virology", + "year": 1990, "referenceCount": 31, "citationCount": 79, "influentialCitationCount": + 1, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc247958?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1990-10-01", "journal": {"volume": + "64", "pages": "4718 - 4725", "name": "Journal of Virology"}, "authors": [{"authorId": + "5260667", "name": "L. Serunian"}, {"authorId": "6603909", "name": "K. Auger"}, + {"authorId": "6665338", "name": "T. Roberts"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "4e9acf3c918479f1ac0585c4cc237e46fc212d0d", "externalIds": + {"MAG": "1975642651", "DOI": "10.1016/0092-8674(89)90182-7", "CorpusId": 22154860, + "PubMed": "2467744"}, "corpusId": 22154860, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/4e9acf3c918479f1ac0585c4cc237e46fc212d0d", + "title": "PDGF-dependent tyrosine phosphorylation stimulates production of + novel polyphosphoinositides in intact cells", "abstract": null, "venue": "Cell", + "year": 1989, "referenceCount": 33, "citationCount": 800, "influentialCitationCount": + 22, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1989-04-07", "journal": {"volume": "57", "pages": "167-175", "name": "Cell"}, + "authors": [{"authorId": "6603909", "name": "K. Auger"}, {"authorId": "5260667", + "name": "L. Serunian"}, {"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": + "145096401", "name": "P. Libby"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "833c06d33753a4c676bad7474647f714e00e12cb", "externalIds": {"MAG": + "2118044213", "PubMedCentral": "2216206", "DOI": "10.1085/JGP.93.2.285", "CorpusId": + 475047, "PubMed": "2467962"}, "corpusId": 475047, "publicationVenue": {"id": + "eb5b7fda-8fd6-48a1-bfed-2aac4b99cbee", "name": "The Journal of General Physiology", + "type": "journal", "alternate_names": ["J Gen Physiol"], "issn": "0022-1295", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=484", + "alternate_urls": ["http://jgp.rupress.org/"]}, "url": "https://www.semanticscholar.org/paper/833c06d33753a4c676bad7474647f714e00e12cb", + "title": "Effects of muscarinic, alpha-adrenergic, and substance P agonists + and ionomycin on ion transport mechanisms in the rat parotid acinar cell. + The dependence of ion transport on intracellular calcium", "abstract": "The + relationship between receptor-mediated increases in the intracellular free + calcium concentration [( Ca]i) and the stimulation of ion fluxes involved + in fluid secretion was examined in the rat parotid acinar cell. Agonist-induced + increases in [Ca]i caused the rapid net loss of up to 50-60% of the total + content of intracellular chloride (Cli) and potassium (Ki), which is consistent + with the activation of calcium-sensitive chloride and potassium channels. + These ion movements were accompanied by a 25% reduction in the intracellular + volume. The relative magnitudes of the losses of Ki and the net potassium + fluxes promoted by carbachol (a muscarinic agonist), phenylephrine (an alpha-adrenergic + agonist), and substance P were very similar to their characteristic effects + on elevating [Ca]i. Carbachol stimulated the loss of Ki through multiple efflux + pathways, including the large-conductance Ca-activated K channel. Carbachol + and substance P increased the levels of intracellular sodium (Nai) to more + than 2.5 times the normal level by stimulating the net uptake of sodium through + multiple pathways; Na-K-2Cl cotransport accounted for greater than 50% of + the influx, and approximately 20% was via Na-H exchange, which led to a net + alkalinization of the cells. Ionomycin stimulated similar fluxes through these + two pathways, but also promoted sodium influx through an additional pathway + which was nearly equivalent in magnitude to the combined uptake through the + other two pathways. The carbachol- induced increase in Nai and decrease in + Ki stimulated the activity of the sodium pump, measured by the ouabain-sensitive + rate of oxygen consumption, to nearly maximal levels. In the absence of extracellular + calcium or in cells loaded with the calcium chelator BAPTA (bis[o- aminophenoxy]ethane-N,N,N'',N''-tetraacetic + acid) the magnitudes of agonist- or ionomycin-stimulated ion fluxes were greatly + reduced. The parotid cells displayed a marked desensitization to substance + P; within 10 min the elevation of [Ca]i and alterations in Ki, Nai, and cell + volume spontaneously returned to near baseline levels. In addition to quantitating + the activation of various ion flux pathways in the rat parotid acinar cell, + these results demonstrate that the activation of ion transport systems responsible + for fluid secretion in this tissue is closely linked to the elevation of [Ca]i.", + "venue": "The Journal of General Physiology", "year": 1989, "referenceCount": + 65, "citationCount": 84, "influentialCitationCount": 6, "isOpenAccess": true, + "openAccessPdf": {"url": "http://jgp.rupress.org/content/93/2/285.full.pdf", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1989-02-01", "journal": + {"volume": "93", "pages": "285 - 319", "name": "The Journal of General Physiology"}, + "authors": [{"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "144664118", + "name": "M. McMillian"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5783113", "name": "E. Cragoe"}, {"authorId": "3683975", "name": "B. Talamo"}]}, + {"paperId": "8b5517878829f57e4375a3e145f6a425c7320acd", "externalIds": {"MAG": + "1938975553", "CorpusId": 23621756, "PubMed": "2553693"}, "corpusId": 23621756, + "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": + "Journal of Biological Chemistry", "type": "journal", "alternate_names": ["J + Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/8b5517878829f57e4375a3e145f6a425c7320acd", + "title": "Polyphosphoinositides produced by phosphatidylinositol 3-kinase + are poor substrates for phospholipases C from rat liver and bovine brain.", + "abstract": "The ability of three pure types of bovine brain phospholipase + C (PLC) and one pure rat liver PLC to utilize as substrates the recently discovered + phosphatidylinositol 3-phosphate (PI-3-P), a putative phosphatidylinositol + 3,4-bisphosphate (PI-3,4-P2), and phosphatidylinositol trisphosphate (PIP3) + was investigated. PI-3-P, PI-3,4-P2, and PIP3 are the products of phosphorylation + of PI, PI-4-P, and PI-4,5-P2, respectively, by phosphoinositide 3-kinase activities + that are associated with certain protein-tyrosine kinases. Although these + new phospholipids have been found in intact cells, PI-3,4-P2 and PIP3 appear + only after stimulation of quiescent cells with growth factors such as platelet-derived + growth factor (Auger, K. R., Serunian, L. A., Soltoff, S. P., Libby, P., and + Cantley, L. C. (1989) Cell 57, 167-175) and after transformation by certain + oncoproteins (L. A. Serunian, K. R. Auger, T. M. Roberts, and L. C. Cantley, + manuscript in preparation). Mixtures of [3H]PI-4-P plus [32P]PI-3-P or [3H]PI-4,5-P2 + plus [32P]PI-3,4-P2 or PIP3 alone were used as substrates for PLCs in vitro. + After incubation with enzyme followed by extraction with chloroform/methanol/HCl, + the ratio of 3H/32P in the aqueous layer revealed the selective hydrolysis + of PI-4-P and PI-4,5-P2 over PI-3-P and PI-3,4-P2. High performance liquid + chromatography analysis of the aqueous layer containing reaction products + confirmed that only PI-4-P and PI-4,5-P2, were hydrolyzed to inositol 1,4-P2 + and inositol 1,4,5-P3, respectively. These findings suggest that the turnover + of PI-3-P, PI-3,4-P2, and PIP3 occurs independently of the turnover of PI-4-P + and PI-4,5-P2.", "venue": "Journal of Biological Chemistry", "year": 1989, + "referenceCount": 0, "citationCount": 180, "influentialCitationCount": 3, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1989-10-25", "journal": {"volume": "264 30", "pages": "\n 17809-15\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "5260667", + "name": "L. Serunian"}, {"authorId": "48688109", "name": "M. T. Haber"}, {"authorId": + "5890639", "name": "T. Fukui"}, {"authorId": "46454995", "name": "J. W. Kim"}, + {"authorId": "3034828", "name": "S. Rhee"}, {"authorId": "3654758", "name": + "J. Lowenstein"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "962591ccd9e5f3b492f957b3cdcb064cb3ae9fbc", "externalIds": {"MAG": "1529762732", + "DOI": "10.1016/s0021-9258(18)83702-4", "CorpusId": 39911699, "PubMed": "2538472"}, + "corpusId": 39911699, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/962591ccd9e5f3b492f957b3cdcb064cb3ae9fbc", + "title": "Characterization and purification of membrane-associated phosphatidylinositol-4-phosphate + kinase from human red blood cells.", "abstract": null, "venue": "Journal of + Biological Chemistry", "year": 1989, "referenceCount": 2, "citationCount": + 77, "influentialCitationCount": 2, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1989-03-25", "journal": {"volume": "264 9", "pages": "\n 5080-8\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "50678030", + "name": "L. Ling"}, {"authorId": "152355108", "name": "J. Schulz"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "9a311dc0a3d841e86a1bee1c8ae905deaedb34e5", + "externalIds": {"MAG": "2005536723", "DOI": "10.1038/342699A0", "CorpusId": + 4358862, "PubMed": "2556641"}, "corpusId": 4358862, "publicationVenue": {"id": + "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/9a311dc0a3d841e86a1bee1c8ae905deaedb34e5", + "title": "The colony stimulating factor-1 receptor associates with and activates + phosphatidylinositol-3 kinase", "abstract": null, "venue": "Nature", "year": + 1989, "referenceCount": 22, "citationCount": 246, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1989-12-07", "journal": + {"volume": "342", "pages": "699-702", "name": "Nature"}, "authors": [{"authorId": + "10119277", "name": "L. Varticovski"}, {"authorId": "122361032", "name": "Brian + Druker"}, {"authorId": "31828216", "name": "D. Morrison"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "48074942", "name": "Thomas Roberts"}]}, + {"paperId": "d1a62b401c71f5790a08f31c2dea535b9914b527", "externalIds": {"MAG": + "2106495708", "DOI": "10.1016/0304-419X(89)90005-X", "CorpusId": 34196580, + "PubMed": "2537660"}, "corpusId": 34196580, "publicationVenue": {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", + "name": "Biochimica et Biophysica Acta", "type": "journal", "alternate_names": + ["Biochim Biophys Acta"], "issn": "0006-3002", "alternate_issns": ["1878-2434"], + "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/d1a62b401c71f5790a08f31c2dea535b9914b527", + "title": "Phosphoinositide metabolism and the control of cell proliferation.", + "abstract": null, "venue": "Biochimica et Biophysica Acta", "year": 1989, + "referenceCount": 125, "citationCount": 138, "influentialCitationCount": 2, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "1989-02-01", "journal": {"volume": "948 3", "pages": "\n 327-44\n ", + "name": "Biochimica et biophysica acta"}, "authors": [{"authorId": "32113608", + "name": "M. Whitman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "f868ca3a398863e6f96a92c7a4d352aa235eb808", "externalIds": {"MAG": "1527514147", + "DOI": "10.1016/s0021-9258(19)47043-9", "CorpusId": 23866260, "PubMed": "2555343"}, + "corpusId": 23866260, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/f868ca3a398863e6f96a92c7a4d352aa235eb808", + "title": "Phosphatidylinositol 3-kinase and its novel product, phosphatidylinositol + 3-phosphate, are present in Saccharomyces cerevisiae.", "abstract": null, + "venue": "Journal of Biological Chemistry", "year": 1989, "referenceCount": + 0, "citationCount": 96, "influentialCitationCount": 2, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1989-12-05", "journal": {"volume": + "264 34", "pages": "\n 20181-4\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "6603909", "name": "K. Auger"}, + {"authorId": "2972505", "name": "C. Carpenter"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "10119277", "name": "L. Varticovski"}]}, {"paperId": + "2e0a5a511f14462ed1cadfb15d830e79b62bc0cb", "externalIds": {"MAG": "2064463412", + "DOI": "10.1021/BI00410A024", "CorpusId": 33815801, "PubMed": "2457390"}, + "corpusId": 33815801, "publicationVenue": {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", + "name": "Biochemistry", "type": "journal", "issn": "0006-2960", "alternate_issns": + ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", "alternate_urls": + ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/2e0a5a511f14462ed1cadfb15d830e79b62bc0cb", + "title": "Location of sites in human lipocortin I that are phosphorylated + by protein tyrosine kinases and protein kinases A and C.", "abstract": "Lipocortin + I is a 39-kilodalton membrane-associated protein that in A431 cells is phosphorylated + on tyrosine in response to epidermal growth factor (EGF). We have used recombinant + human lipocortin I as a substrate for several protein kinases and identified + phosphorylated residues by a combination of peptide mapping and sequence analysis. + Lipocortin I was phosphorylated near the amino terminus at Tyr-21 by recombinant + pp60c-src. The same tyrosine residue was phosphorylated by polyoma middle + T/pp60c-src complex, by recombinant pp50v-abl, and with A431 cell membranes + by the EGF receptor/kinase. The primary site of phosphorylation by protein + kinase C was also near the amino terminus at Ser-27. The major site of phosphorylation + by adenosine cyclic 3'',5''-phosphate dependent protein kinase was on the + carboxy-terminal half of the molecule at Thr-216. These sites are compared + to the phosphorylation sites previously located in the structurally related + protein lipocortin II.", "venue": "Biochemistry", "year": 1988, "referenceCount": + 35, "citationCount": 90, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1988-05-17", "journal": {"volume": "27 10", "pages": "\n 3682-90\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "10119277", "name": "L. + Varticovski"}, {"authorId": "8044764", "name": "S. Chahwala"}, {"authorId": + "32113608", "name": "M. Whitman"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "40386317", "name": "D. Schindler"}, {"authorId": "143918133", + "name": "E. Chow"}, {"authorId": "37411304", "name": "L. K. Sinclair"}, {"authorId": + "5562211", "name": "R. Pepinsky"}]}, {"paperId": "30bbb2b5fadd900c508bfe05722ca55649f6e389", + "externalIds": {"MAG": "2340979889", "DOI": "10.1152/AJPCELL.1988.255.4.C531", + "CorpusId": 45736808, "PubMed": "3177626"}, "corpusId": 45736808, "publicationVenue": + {"id": "998813ea-da72-494a-90fc-783751929f3c", "name": "American Journal of + Physiology", "type": "journal", "alternate_names": ["Am J Physiol"], "issn": + "0002-9513", "alternate_issns": ["2163-5773"], "url": "http://search.epnet.com/direct.asp?db=aph&jid=AHY", + "alternate_urls": ["http://www.physiology.org/", "http://www.physiology.org/journal/ajplegacy", + "https://www.physiology.org/journal/ajpcell", "http://ajpcon.physiology.org/", + "https://www.biodiversitylibrary.org/bibliography/38917"]}, "url": "https://www.semanticscholar.org/paper/30bbb2b5fadd900c508bfe05722ca55649f6e389", + "title": "Cell cycle dependence of inositol phosphate levels in neuroblastoma + cells.", "abstract": "To investigate the timing of inositol lipid turnover + in relation to the cell cycle, inositol phosphates and lipids were measured + in neuroblastoma (Neuro-2A) cells that were prelabeled with [3H]inositol and + synchronized by a mitotic shakeoff technique. Distinct early and late phases + of inositol phosphate production were identified. The early peak occurs between + the 2nd and 4th hour after mitosis near the G1/S transition. A later peak + occurs around the peak of S phase (DNA synthesis) at 7-8 h after mitosis. + These findings suggest that activation of phosphatidylinositol turnover generates + signals that play a role in cell cycle progression.", "venue": "American Journal + of Physiology", "year": 1988, "referenceCount": 26, "citationCount": 5, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1988-10-01", "journal": {"volume": "255 4 Pt 1", "pages": "\n C531-5\n ", + "name": "The American journal of physiology"}, "authors": [{"authorId": "4459392", + "name": "L. Fleischman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "420e719f6076d2aae02650579b06ee4b49e9ec90", "externalIds": {"MAG": + "2039744950", "DOI": "10.1146/annurev.physiol.50.1.205", "CorpusId": 84417138}, + "corpusId": 84417138, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/420e719f6076d2aae02650579b06ee4b49e9ec90", + "title": "Cell and molecular physiology. Modulation of membrane transport + systems", "abstract": null, "venue": "", "year": 1988, "referenceCount": 0, + "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": null, "authors": + [{"authorId": "4742485", "name": "J. Hoffman"}, {"authorId": "4324390", "name": + "S. Soltoff"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "5839611", "name": "P. Weer"}, {"authorId": "5028893", "name": "D. Gadsby"}, + {"authorId": "144647718", "name": "R. Rakowski"}, {"authorId": "144999726", + "name": "H. Kaback"}, {"authorId": "7612148", "name": "A. Carruthers"}, {"authorId": + "4377194", "name": "D. Melchior"}, {"authorId": "3234098", "name": "T. Tsong"}, + {"authorId": "2450724", "name": "R. Astumian"}, {"authorId": "3929882", "name": + "D. Yingst"}]}, {"paperId": "568951378ddfba2d59712a23383ab16a46b978c6", "externalIds": + {"MAG": "1591713964", "DOI": "10.1016/s0021-9258(19)35398-0", "CorpusId": + 25676403, "PubMed": "2826456"}, "corpusId": 25676403, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/568951378ddfba2d59712a23383ab16a46b978c6", + "title": "CV-1 cell recipients of the mouse ouabain resistance gene express + a ouabain-insensitive Na,K-ATPase after growth in cardioactive steroids.", + "abstract": null, "venue": "Journal of Biological Chemistry", "year": 1988, + "referenceCount": 0, "citationCount": 5, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1988-01-15", "journal": {"volume": + "263 2", "pages": "\n 624-32\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "152355108", "name": "J. + Schulz"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "5da7fa85f7bcbfe706fbc1deb773f39a44a6ec97", + "externalIds": {"MAG": "106302169", "CorpusId": 43154169, "PubMed": "2848507"}, + "corpusId": 43154169, "publicationVenue": {"id": "64838252-a209-4424-a778-3b86b4a83c48", + "name": "Biochemical Journal", "type": "journal", "alternate_names": ["Biochem + J"], "issn": "0264-6021", "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, + "url": "https://www.semanticscholar.org/paper/5da7fa85f7bcbfe706fbc1deb773f39a44a6ec97", + "title": "Extracellular ATP increases free cytosolic calcium in rat parotid + acinar cells. Differences from phospholipase C-linked receptor agonists.", + "abstract": "The effects of extracellular ATP on intracellular free calcium + concentration [( Ca2+]i), phosphatidylinositol (PtdIns) turnover, amylase + release and Ca2+-activated membrane currents were examined in isolated rat + parotid acinar cells and contrasted with the effects of receptor agonists + known to activate phospholipase C. ATP was more effective than muscarinic + and alpha-adrenergic agonists and substance P as a stimulus for elevating + [Ca2+]i (as measured with quin2). The ATP effect was selectively antagonized + by pretreating parotid cells with the impermeant anion-exchange blocker 4,4''-di-isothiocyano-2,2''-stilbenedisulphonate + (DIDS), which also inhibited binding of [alpha-32P]ATP to parotid cells. By + elevating [Ca2+]i, ATP and the muscarinic agonist carbachol both activated + Ca2+-sensitive membrane currents, which were measured by whole-cell and cell-attached + patch-clamp recordings. However, there were marked contrasts between the effects + of ATP and the receptor agonists linked to phospholipase C, as follows. (1) + Although the combination of maximally effective concentrations of carbachol, + substance P and phenylephrine had no greater effect on [Ca2+]i than did carbachol + alone, there was some additivity between maximal ATP and carbachol effects. + (2) Intracellular dialysis with guanosine 5''-[beta-thio]diphosphate did not + block activation of ion channels by ATP, but did block channel activation + by the muscarinic agonist carbachol. This suggests that a G-protein is involved + in the muscarinic response, but not in the response to ATP. (3) Despite its + pronounced effect on [Ca2+]i, ATP had little effect on PtdIns turnover in + these cells, in contrast with the effects of carbachol and other Ca2+-mobilizing + agents. (4) Although ATP was able to stimulate amylase release from parotid + acinar cells, the stimulation was only 33 +/- 9% of that obtained with phospholipase + C-linked receptor agonists. These differences suggest that ATP increases [Ca2+]i + through specific activation of a pathway which is distinct from that shared + by the classical phospholipase C-linked receptor agonists.", "venue": "Biochemical + Journal", "year": 1988, "referenceCount": 0, "citationCount": 97, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1988-10-01", "journal": {"volume": + "255 1", "pages": "\n 291-300\n ", "name": "The Biochemical + journal"}, "authors": [{"authorId": "144664118", "name": "M. McMillian"}, + {"authorId": "4324390", "name": "S. Soltoff"}, {"authorId": "144776879", "name": + "J. Lechleiter"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3683975", "name": "B. Talamo"}]}, {"paperId": "6b5de5123efd8a796ed2c870754af8ace3fcb262", + "externalIds": {"DOI": "10.1007/BF02919091", "CorpusId": 198225131}, "corpusId": + 198225131, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/6b5de5123efd8a796ed2c870754af8ace3fcb262", + "title": "From meetings", "abstract": null, "venue": "", "year": 1988, "referenceCount": + 0, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": + "Mathematics", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": {"volume": "18", "pages": "330-373", "name": "Ricerca in + clinica e in laboratorio"}, "authors": [{"authorId": "5933076", "name": "I. + Arias"}, {"authorId": "118265567", "name": "A. J\u00e9z\u00e9quel"}, {"authorId": + "2060736759", "name": "P. Berg"}, {"authorId": "2805899", "name": "A. Gatta"}, + {"authorId": "118664996", "name": "P. Angeli"}, {"authorId": "5047464", "name": + "B. Galanti"}, {"authorId": "144936110", "name": "G. Gaeta"}, {"authorId": + "120787627", "name": "C. Gallo"}, {"authorId": "145318321", "name": "G. Giusti"}, + {"authorId": "2081288527", "name": "C. Pourcel"}, {"authorId": "4550486", + "name": "A. Zignego"}, {"authorId": "2051645", "name": "C. Br\u00e9chot"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5616087", "name": + "M. Rizzetto"}, {"authorId": "4329279", "name": "R. Mazzanti"}, {"authorId": + "3810221", "name": "S. Moscarella"}, {"authorId": "3356672", "name": "P. Gentilini"}, + {"authorId": "11428061", "name": "G. Buzzelli"}, {"authorId": "14011613", + "name": "C. Smorlesi"}, {"authorId": "34576755", "name": "P. Dattolo"}, {"authorId": + "13756706", "name": "G. Focardi"}, {"authorId": "4132949", "name": "G. Laffi"}, + {"authorId": "35153679", "name": "E. Meacci"}, {"authorId": "3338065", "name": + "F. Marra"}, {"authorId": "2055821366", "name": "T. Reynolds"}, {"authorId": + "2071055800", "name": "V. Arroyo"}, {"authorId": "6466373", "name": "G. T. + Haupert"}, {"authorId": "6140128", "name": "A. Gerbes"}, {"authorId": "10119277", + "name": "L. Varticovski"}, {"authorId": "3245818", "name": "N. Villari"}, + {"authorId": "48627488", "name": "S. Bartoletti"}, {"authorId": "6759392", + "name": "M. Strazzabosco"}, {"authorId": "5439418", "name": "M. Muraca"}, + {"authorId": "102183061", "name": "M. Venuti"}, {"authorId": "80536931", "name": + "A. Varotto"}, {"authorId": "4823916", "name": "R. Iemmolo"}, {"authorId": + "79710689", "name": "A. Fragasso"}, {"authorId": "15885247", "name": "D. Passera"}, + {"authorId": "11481605", "name": "L. Okolics\u00e0nyi"}, {"authorId": "6673479", + "name": "L. Capocaccia"}, {"authorId": "15244710", "name": "F. Ariosto"}, + {"authorId": "143882801", "name": "M. Merli"}, {"authorId": "5827445", "name": + "O. Riggio"}, {"authorId": "144872574", "name": "A. Romiti"}, {"authorId": + "6012728", "name": "L. Pagliaro"}, {"authorId": "1393649265", "name": "G. + D\u2019Amico"}, {"authorId": "4372293", "name": "M. Traina"}, {"authorId": + "5907570", "name": "L. Montalbano"}, {"authorId": "3319034", "name": "G. Gatto"}, + {"authorId": "4194472", "name": "R. Pisa"}, {"authorId": "7204493", "name": + "S. Maisano"}, {"authorId": "4960432", "name": "F. Politi"}, {"authorId": + "2878630", "name": "P. Colletti"}, {"authorId": "5813229", "name": "F. Tin\u00e9"}, + {"authorId": "143653588", "name": "L. Barbara"}, {"authorId": "4689162", "name": + "R. Corinaldesi"}, {"authorId": "3666705", "name": "R. Giorgio"}, {"authorId": + "3764545", "name": "V. Stanghellini"}, {"authorId": "7495889", "name": "L. + Scuro"}, {"authorId": "6063806", "name": "I. Vantini"}, {"authorId": "7407346", + "name": "G. Dobrilla"}, {"authorId": "10331365", "name": "S. Amplatz"}, {"authorId": + "5052234", "name": "R. Naccarato"}, {"authorId": "83442733", "name": "F. Mario"}, + {"authorId": "145503196", "name": "A. Blasi"}, {"authorId": "5269597", "name": + "A. Mangiameli"}, {"authorId": "47442841", "name": "G. Bianchi porro"}, {"authorId": + "2237164", "name": "M. Petrillo"}, {"authorId": "66110219", "name": "M. Forg\u00e1c"}, + {"authorId": "5469802", "name": "M. Donowitz"}, {"authorId": "49027465", "name": + "R. Rood"}, {"authorId": "32150266", "name": "J. Wesolek"}, {"authorId": "14115329", + "name": "E. Emmer"}, {"authorId": "143827072", "name": "M. Cohen"}, {"authorId": + "50308731", "name": "J. McCullen"}, {"authorId": "145235879", "name": "R. + Braithwaite"}, {"authorId": "35359539", "name": "G. Sharp"}, {"authorId": + "4082230", "name": "H. Murer"}, {"authorId": "77333781", "name": "H. D. Ward"}, + {"authorId": "2140477333", "name": "M. Pereira"}]}, {"paperId": "7a7ad425fc39d1f8f200b547c00b2fed98523261", + "externalIds": {"MAG": "2153534403", "DOI": "10.1146/ANNUREV.PH.50.030188.001231", + "CorpusId": 26846658, "PubMed": "2454071"}, "corpusId": 26846658, "publicationVenue": + {"id": "eedc6e61-e846-485a-a273-0cc8bb06d7d3", "name": "Annual Review of Physiology", + "type": "journal", "alternate_names": ["Annu Rev Physiol"], "issn": "0066-4278", + "url": "https://www.annualreviews.org/journal/physiol", "alternate_urls": + ["https://www.annualreviews.org/loi/physiol", "http://physiol.annualreviews.org/", + "http://arjournals.annualreviews.org/loi/physiol"]}, "url": "https://www.semanticscholar.org/paper/7a7ad425fc39d1f8f200b547c00b2fed98523261", + "title": "Mitogens and ion fluxes.", "abstract": "The response of growth-arrested + cells to a variety of growth factors and pharmacological mitogens involves + a cascade of biochemical and ionic changes that occur within minutes and are + believed to play critical roles in the initiation of cell proliferation. In + general, investigations of these phenomena have used proliferating cells in + culture that can be made to reversibly enter the nonproliferative Go/Gt state, + usually by the withdrawal of serum. The bio\u00ad chemical changes observed + within the first few minutes of the addition of growth factors and mitogens + include protein phosphorylation, an increased turnover of inositol lipids, + and increased transcription of several proto\u00ad oncogenes. The ionic alterations + include rapid increases in the cytosolic free calcium concentration ([Ca2+l) + from intracellular calcium stores andlor ,via influx through channels in the + plasma membrane and the stimulation of the plasma membrane Na+ -H+ exchanger, + which promotes an increase in sodium influx and cytoplasmic alkalinization. + The relationship between these early changes and the increase in DNA synthesis + that occurs many hours later is a key question in the understanding of mitogenesis. + This article focuses on the alterations in ion fluxes that have been observed + in response to mitogens in a variety of cells. In addition, the association + of biochemical events with ion fluxes and the association of these eady events + with the subsequent initiation of DNA synthesis are discussed. Important considerations + that arc addressed are whether there are multiple pathways by which different + mitogens induce proliferation and whether a single mitogen can induce proliferation + by multi\u00ad ple pathways.", "venue": "Annual Review of Physiology", "year": + 1988, "referenceCount": 51, "citationCount": 96, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + null, "journal": {"volume": "50", "pages": "\n 207-23\n ", + "name": "Annual review of physiology"}, "authors": [{"authorId": "4324390", + "name": "S. Soltoff"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "831cd0bf50765d0cf08d236f62df8b6548f76d80", "externalIds": {"MAG": "2485622678", + "DOI": "10.1515/9783110846713.340", "CorpusId": 102455003}, "corpusId": 102455003, + "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/831cd0bf50765d0cf08d236f62df8b6548f76d80", + "title": "INCREASE IN [Ca2+]i IN CULTURED HUMAN KERATINOCYTES BY 1,25(OH)2D3 + IS CALCIUM DEPENDENT AND COINCIDES WITH AN INCREASE IN PHOSPHATIDYLINOSITOL + METABOLISM.", "abstract": null, "venue": "", "year": 1988, "referenceCount": + 1, "citationCount": 0, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "1988-01-31", + "journal": {"volume": "", "name": ""}, "authors": [{"authorId": "145531353", + "name": "J. MacLaughlin"}, {"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4873870", "name": "M. Holick"}]}, {"paperId": "9c23ce7db2c9ba311c9e584892c951cfcf78c025", + "externalIds": {"MAG": "2017499074", "DOI": "10.1038/332644A0", "CorpusId": + 4326568, "PubMed": "2833705"}, "corpusId": 4326568, "publicationVenue": {"id": + "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/9c23ce7db2c9ba311c9e584892c951cfcf78c025", + "title": "Type I phosphatidylinositol kinase makes a novel inositol phospholipid, + phosphatidylinositol-3-phosphate", "abstract": null, "venue": "Nature", "year": + 1988, "referenceCount": 15, "citationCount": 930, "influentialCitationCount": + 38, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle", "Study"], "publicationDate": "1988-04-14", + "journal": {"volume": "332", "pages": "644-646", "name": "Nature"}, "authors": + [{"authorId": "32113608", "name": "M. Whitman"}, {"authorId": "144639842", + "name": "C. Downes"}, {"authorId": "40332617", "name": "M. Keeler"}, {"authorId": + "47254988", "name": "T. Keller"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "dce25b42f36ae7528fd335f286e9dab1eb73ddcd", "externalIds": {"MAG": + "2026101018", "DOI": "10.1111/j.1749-6632.1988.tb22357.x", "CorpusId": 20394909, + "PubMed": "2854424"}, "corpusId": 20394909, "publicationVenue": {"id": "fa1f0815-0811-4291-b4fc-8230a6c9bf5b", + "name": "Annals of the New York Academy of Sciences", "type": "journal", "alternate_names": + ["Ann n y Acad Sci"], "issn": "0077-8923", "url": "http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1749-6632", + "alternate_urls": ["http://www.annalsnyas.org/", "http://www.nyas.org/publications/annals/default.aspx", + "https://onlinelibrary.wiley.com/journal/17496632"]}, "url": "https://www.semanticscholar.org/paper/dce25b42f36ae7528fd335f286e9dab1eb73ddcd", + "title": "Growth Factor and Oncogene Influences on Cell Growth Regulation", + "abstract": "Efforts to understand the mechanisms that control cell growth + have, in a variety of scientific fields, stimulated research in which different + cell types and proliferative agents such as retroviruses and mitogens are + used. Progress in unraveling the complexities of growth regulation has been + facilitated by studies of growth factor receptor structure, viral oncogenes, + and their cellular homologues called protooncogenes. Moreover, the realization + that cell transformation involves the same biochemical processes that regulate + nontransformed cell growth, but with loss of the normal restraints, has provided + new insights into the mechanisms of cell proliferation. Recent biochemical + and molecular information about growth factors and their receptors has shed + light on their relationships to both normal and abnormal cell growth. Several + peptide growth factor receptors have now been purified and, with a few notable + exceptions, constitute a family of homologous proteins with growth-factorstimulated + tyrosine kinase activities. These tryosine kinases undergo autophosphorylation, + which appears to be critical for their regulation; other physiologically relevant + targets of these tyrosine kinases have not yet been determined. Furthermore, + the peptide growth factor receptors that have been purified are structurally + very distinct from the hormone receptors whose signals are known to be transduced + by GTP-binding proteins. In spite of the structural similarities among growth + factor receptors, the primary responses to different growth factors are quite + distinct. For example, whereas a t least some of the primary responses to + platelet-derived growth factor (PDGF) and bombesin are due to elevation of + second messengers produced from turnover of products in the phosphatidylinositol + (PI) pathway, many other growth factors do not appear to involve the classical + PI pathway. Recent evidence that insulin stimulates the production of a novel + second messenger derived from glycosylated PI raises the interesting possibility + that other growth factors may act through other novel second-messenger molecules + derived from PI. A link between elevation of second messengers and the growth + response is based primarily on activators of protein kinase C that affect + cell proliferation. However, this activation only partially explains growth + responses to some factors and is irrelevant to growth responses to other factors. + Like certain growth factor receptors, may oncoproteins are enzymes with proteintyrosine + kinase activity toward as yet unidentified target molecules which, in turn, + convey a growth signal to the cell nucleus. In contrast, a distinct subset + of oncoproteins target directly to the nucleus, where at least some are thought + to act as specific", "venue": "Annals of the New York Academy of Sciences", + "year": 1988, "referenceCount": 45, "citationCount": 5, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + "1988-12-01", "journal": {"volume": "551", "name": "Annals of the New York + Academy of Sciences"}, "authors": [{"authorId": "5260667", "name": "L. Serunian"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "33f573f8e3b629702c0e2135226aea851582e317", + "externalIds": {"MAG": "123919963", "CorpusId": 30001443, "PubMed": "2835058"}, + "corpusId": 30001443, "publicationVenue": {"id": "e441f16f-e93a-44b5-8dfb-e035124977e2", + "name": "Anti-Cancer Drug Design", "type": "journal", "alternate_names": ["Anti-cancer + Drug Design", "Anti-cancer Drug Des"], "issn": "0266-9536"}, "url": "https://www.semanticscholar.org/paper/33f573f8e3b629702c0e2135226aea851582e317", + "title": "The role of lipid-derived second messengers in cell growth and transformation.", + "abstract": "Recent information on the structure of growth factor receptors + and oncogenes has advanced our understanding of the biochemical mechanism + of growth control. Several peptide growth factor receptors have now been purified + and, with a few notable exceptions, they fall into a family of homologous + proteins with growth factor-stimulated protein-tyrosine kinase (PTK) activity. + Mutations in the genes encoding for both the growth factors and the growth + factor receptors of this family have been shown to cause cell transformation. + Thus, PTKs have been implicated both in normal growth control and in cell + transformation. The critical targets for these PTKs have not been determined. + Several but not all growth factors stimulate production of the phosphatidylinositol + (PI)-derived second messengers, diacylglycerol and inositol-1,4,5-trisphosphate. + By purifying and characterizing the enzymes involved in PI turnover we are + attempting to determine how this system is regulated by growth factors and + oncogene products. We have found that fibroblasts contain two distinct PI + kinases, and that one of these enzymes can be precipitated with antibodies + against phosphotyrosine only after addition of platelet-derived growth factor. + The relevance of the PI turnover pathway in propagation of growth signals + is discussed.", "venue": "Anti-Cancer Drug Design", "year": 1987, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1987-10-01", "journal": + {"volume": "2 2", "pages": "\n 129-38\n ", "name": "Anti-cancer + drug design"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "4459392", "name": "L. Fleischman"}, {"authorId": "32113608", + "name": "M. Whitman"}]}, {"paperId": "6b9937082a77dc23aeef7c79f23262ba569ce5de", + "externalIds": {"MAG": "2029201128", "DOI": "10.1021/BI00376A037", "CorpusId": + 29272153, "PubMed": "3548823"}, "corpusId": 29272153, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/6b9937082a77dc23aeef7c79f23262ba569ce5de", + "title": "Kinetic analysis of guanosine 5''-O-(3-thiotriphosphate) effects + on phosphatidylinositol turnover in NRK cell homogenates.", "abstract": "Addition + of the guanine nucleotide analogue guanosine 5''-O-(3-thiotriphosphate) (GTP + gamma S) to [3H]inositol-labeled NRK cell homogenates resulted in rapid breakdown + of cellular polyphosphoinositides. GTP gamma S stimulated phospholipase C, + resulting in a more than 4-fold increase in the hydrolysis rates of phosphatidylinositol + 4-phosphate (PIP) and phosphatidylinositol 4,5-bis(phosphate) (PIP2). No significant + effect of GTP gamma S on direct phosphatidylinositol (PI) hydrolysis was detected. + There was an increase in water-soluble inositols, with inositol tris(phosphate) + (IP3) levels increasing at least 10 times over the decrease seen in PIP2, + indicating that PIP kinase activity was also accelerated following GTP gamma + S addition. Inositol 1,4,5-tris(phosphate) peaked rapidly after GTP gamma + S addition (less than 2 min) while inositol 1,3,4-tris-(phosphate) was produced + more slowly and leveled off after approximately 10 min. The differential equations + describing conversion between intermediates in the PI turnover pathway were + solved and fitted to data obtained from both [3H]inositol and [32P]phosphate + fluxes by nonlinear least-squares analysis. GTP gamma S effects on the pseudo-first-order + rate constants for the lipase, kinase, and phosphatase steps were determined + from the analysis. From these measurements it can be estimated that, in the + presence of GTP gamma S and calcium buffered to 130 nM, hydrolysis of PIP2 + accounts for at least 10 times as much diacylglycerol as direct PI breakdown + despite the 100-fold excess of PI over PIP2. From the kinetic model it is + predicted that small changes in the activities of PI and PIP kinases can have + large but different effects on the level of IP3 and diacylglycerol following + GTP gamma S addition. These results argue that regulation of PI and PIP kinases + may be important for determining both cellular IP3 and diacylglycerol levels.", + "venue": "Biochemistry", "year": 1987, "referenceCount": 40, "citationCount": + 20, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1987-01-27", "journal": {"volume": "26 2", "pages": "\n 612-22\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "8044764", "name": "S. Chahwala"}, + {"authorId": "4459392", "name": "L. Fleischman"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "73506ded20f72635d68a3a8a4b4be80748e4a63a", + "externalIds": {"MAG": "2094116330", "DOI": "10.1021/BI00395A039", "CorpusId": + 34559516, "PubMed": "2827737"}, "corpusId": 34559516, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/73506ded20f72635d68a3a8a4b4be80748e4a63a", + "title": "Bovine brain contains two types of phosphatidylinositol kinase.", + "abstract": "Two phosphatidylinositol (PI) kinases from bovine brain were + separated by rate zonal sucrose gradient centrifugation of detergent-solubilized + membranes. Of the total PI kinase activity, 43% migrates on sucrose gradients + with a size of approximately 55 kilodaltons (kDa); this kinase has properties + similar to one of two PI kinase activities characterized in fibroblasts [Whitman, + M., Kaplan, D. R., Roberts, T., & Cantley, L. (1987) Biochem. J. (in press)] + and has been termed type 2. The remainder of the activity migrates in a second + peak with a size of approximately 230 kDa. This enzyme possesses properties + which are unlike both fibroblast PI kinase activities and has been termed + type 3. The type 2 and type 3 enzymes have very different affinities for adenine + nucleotides and are readily distinguishable by their sensitivities to inhibition + by adenosine. The KMs of types 2 and 3 kinases for ATP are 54 and 742 microM, + and the Kis for adenosine are 18 and 1520 microM, respectively. The two enzymes + also differ in their affinities for PI, phosphatidylinositol 4-phosphate, + and Mg2+ as well as in stimulation and inhibition by other phospholipids. + When PI kinase from erythrocyte ghosts is fractionated by sucrose gradient + centrifugation, only one peak of activity is observed which is indistinguishable + from brain type 2 PI kinase.", "venue": "Biochemistry", "year": 1987, "referenceCount": + 31, "citationCount": 97, "influentialCitationCount": 2, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1987-10-20", "journal": {"volume": "26 21", "pages": "\n 6845-52\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "10330714", "name": "G. + Endemann"}, {"authorId": "90552269", "name": "S. Dunn"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "7ec9910fa2854b9c9f0915a51f4d981ce77fd659", + "externalIds": {"MAG": "2149452654", "DOI": "10.1161/01.HYP.10.5_PT_2.I93", + "CorpusId": 27854076, "PubMed": "2824373"}, "corpusId": 27854076, "publicationVenue": + {"id": "066fa0b1-bbd7-4e12-a6ad-cafd76ba0811", "name": "HYPERTENSION", "type": + "journal", "alternate_names": ["Hypertension"], "issn": "2224-1485", "alternate_issns": + ["0194-911X"], "url": "http://hypertension.zaslavsky.com.ua/", "alternate_urls": + ["http://hyper.ahajournals.org/", "http://ovidsp.ovid.com/ovidweb.cgi?AN=00004268-000000000-00000&CSC=Y&D=yrovft&NEWS=n&PAGE=toc&T=JS"]}, + "url": "https://www.semanticscholar.org/paper/7ec9910fa2854b9c9f0915a51f4d981ce77fd659", + "title": "Membrane biochemistry of the ouabain-resistant potassium transport + system.", "abstract": "A 6.5-kilobase fragment of genomic DNA from mutant + mouse cells under ouabain selection pressure conferred ouabain resistance + when transfected into ouabain-sensitive CV1 green monkey fibroblasts. Ouabain + resistance was induced in the presence of 10 microM ouabain. Amiloride (500 + microM) completely blocked ouabain-insensitive 86Rb+ uptake into these cells. + Plasma membranes from these cells demonstrated little sodium-dependent adenosine + triphosphatase (ATPase) activity but had potassium-dependent and ouabain-resistant + p-nitrophenylphosphatase activity. Like Na+,K+-ATPase this activity was vanadate- + and sodium-inhibitable. Also, like the Na+,K+-ATPase, sodium inhibition of + the p-nitrophenylphosphatase was reversed by 10 microM adenosine 5''-triphosphate.", + "venue": "HYPERTENSION", "year": 1987, "referenceCount": 8, "citationCount": + 0, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1987-11-01", "journal": {"volume": "10 5 Pt 2", "pages": "\n I93-4\n ", + "name": "Hypertension"}, "authors": [{"authorId": "34784769", "name": "L. + English"}, {"authorId": "33469167", "name": "B. White"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "a1d1b7a4adc579f3aeb7b2c7c18da65ec28c0c12", + "externalIds": {"MAG": "2260076009", "DOI": "10.1042/BJ2470165", "CorpusId": + 20432411, "PubMed": "2825654"}, "corpusId": 20432411, "publicationVenue": + {"id": "64838252-a209-4424-a778-3b86b4a83c48", "name": "Biochemical Journal", + "type": "journal", "alternate_names": ["Biochem J"], "issn": "0264-6021", + "alternate_issns": ["0006-2936"], "url": "http://www.biochemj.org/"}, "url": + "https://www.semanticscholar.org/paper/a1d1b7a4adc579f3aeb7b2c7c18da65ec28c0c12", + "title": "Evidence for two distinct phosphatidylinositol kinases in fibroblasts. + Implications for cellular regulation.", "abstract": "Phosphatidylinositol + (PtdIns) kinase activities from non-transformed and polyoma-middle-T-transformed + murine fibroblasts were examined. Both normal and transformed 3T3 fibroblasts + have two PtdIns kinases, which can be separated by anion-exchange chromatography. + One of these activities (Type I) has a Km for ATP of 10 microM, is resistant + to inhibition by adenosine, AMP or ADP, and is inhibited by non-ionic detergents. + The other activity (Type II) has a somewhat higher Km for ATP (35 microM) + and is inhibited competitively by ADP, AMP and adenosine at concentrations + suggesting regulation of this activity by the energy charge of the cell. The + Type II PtdIns kinase is activated by non-ionic detergents. We have previously + reported the specific association of a PtdIns kinase activity with polyoma-middle-T + immunoprecipitates [Whitman, Kaplan, Schaffhausen, Cantley & Roberts (1985) + Nature (London) 315, 239-242; Kaplan, Whitman, Schaffhausen, Raptis, Garcea, + Pallas, Roberts & Cantley (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3624-3628]. + Comparison of the immunoprecipitated PtdIns kinase with the activities identified + by ion-exchange chromatography indicates that it is the Type I enzyme which + specifically associates with the middle-T/pp60c-src complex. This PtdIns kinase + activity is separable from both middle T and pp60c-src. Type I PtdIns kinase + also associates with pp60v-src immunoprecipitates from Rous-sarcoma-virus-transformed + cells. Furthermore, this PtdIns kinase appears to co-precipitate with partially + purified platelet derived growth factor (PDGF) receptor. The amount of this + activity found in anti-phosphotyrosine immunoprecipitates or in wheat-germ-lectin-agarose + precipitates is increased 50-fold by stimulation of quiescent Balb/C 3T3 fibroblasts + with PDGF. These results suggest that the Type I PtdIns kinase is regulated + by agents which affect cell growth and transformation, whereas the Type II + PtdIns kinase may be regulated by the local [ATP]/[ADP] ratio.", "venue": + "Biochemical Journal", "year": 1987, "referenceCount": 2, "citationCount": + 206, "influentialCitationCount": 2, "isOpenAccess": true, "openAccessPdf": + {"url": "https://europepmc.org/articles/pmc1148384?pdf=render", "status": + null}, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1987-10-01", "journal": {"volume": "247 1", "pages": "\n 165-74\n ", + "name": "The Biochemical journal"}, "authors": [{"authorId": "32113608", "name": + "M. Whitman"}, {"authorId": "32389352", "name": "D. Kaplan"}, {"authorId": + "6665338", "name": "T. Roberts"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "f15c813981dcfab217717b4a45425931cab89c59", "externalIds": {"MAG": + "2062602000", "DOI": "10.1016/0006-291X(87)90399-8", "CorpusId": 37332388, + "PubMed": "3426590"}, "corpusId": 37332388, "publicationVenue": {"id": "1a9c698b-7fe4-4444-b391-208b4b2326e2", + "name": "Biochemical and Biophysical Research Communications - BBRC", "type": + "journal", "alternate_names": ["Biochem Biophys Res Commun", "Biochemical + and Biophysical Research Communications", "Biochem Biophys Res Commun BBRC"], + "issn": "0006-291X", "url": "http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description", + "alternate_urls": ["http://www.idealibrary.com/links/toc/bbrc", "https://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/", + "http://www.sciencedirect.com/science/journal/0006291X"]}, "url": "https://www.semanticscholar.org/paper/f15c813981dcfab217717b4a45425931cab89c59", + "title": "Extracellular ATP elevates intracellular free calcium in rat parotid + acinar cells.", "abstract": null, "venue": "Biochemical and Biophysical Research + Communications - BBRC", "year": 1987, "referenceCount": 17, "citationCount": + 42, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1987-12-16", "journal": {"volume": "149 2", "pages": "\n 523-30\n ", + "name": "Biochemical and biophysical research communications"}, "authors": + [{"authorId": "144664118", "name": "M. McMillian"}, {"authorId": "4324390", + "name": "S. Soltoff"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "3683975", "name": "B. Talamo"}]}, {"paperId": "020866d124a5e04cda4d33112890966d4a59d0ae", + "externalIds": {"MAG": "1506627435", "CorpusId": 45199369, "PubMed": "3003059"}, + "corpusId": 45199369, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/020866d124a5e04cda4d33112890966d4a59d0ae", + "title": "Delta endotoxin is a potent inhibitor of the (Na,K)-ATPase.", "abstract": + "A 68-kDa protein, delta endotoxin, produced by Bacillus thuringiensis ssp. + Kurstaki inhibits ion transport, (Na,K)-ATPase, and K+-p-nitrophenylphosphatase + activity catalyzed by the Na+ pump. The Ki for inhibition of the K+-p-nitrophenylphosphatase + activity of purified dog kidney (Na,K)-ATPase was approximately 0.37 microM. + Delta endotoxin had a similar Ki for inhibition of (Na,K)-ATPase activity + when assayed at low Na+ concentration (10 mM) but the inhibition was reversed + when high concentrations of Na+ (100 mM NaCl) were added to the assay. Phosphorylation + of the active site aspartyl residue with 32PO3-4 was also blocked by delta + endotoxin. Ouabain-sensitive 86Rb+ uptake into intact human red blood cells + was not inhibited by externally added toxin; however, strophanthidin-inhibitable + 22Na+ uptake into inside-out vesicles from red blood cells was completely + blocked by delta endotoxin (Ki = 0.73 microM). These data suggest that delta + endotoxin must enter the cell before it can inhibit the Na+ pump.", "venue": + "Journal of Biological Chemistry", "year": 1986, "referenceCount": 4, "citationCount": + 38, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1986-01-25", "journal": {"volume": "261 3", "pages": "\n 1170-3\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "34784769", + "name": "L. English"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "0eea62e1f266f8b86ac52ade7ee3ceb70e9f62d2", "externalIds": {"MAG": "2136900732", + "DOI": "10.1146/ANNUREV.BI.55.070186.002455", "CorpusId": 36746866, "PubMed": + "3527050"}, "corpusId": 36746866, "publicationVenue": {"id": "9e5ab0fc-a36d-4a05-bc89-12dd1cb12e2b", + "name": "Annual Review of Biochemistry", "type": "journal", "alternate_names": + ["Annu Rev Biochem"], "issn": "0066-4154", "url": "https://www.annualreviews.org/journal/biochem", + "alternate_urls": ["http://www.annualreviews.org/journal/biochem", "http://biochem.annualreviews.org/", + "https://www.annualreviews.org/loi/biochem", "http://intl-biomedical.annualreviews.org/", + "http://arjournals.annualreviews.org/loi/biochem", "http://arjournals.annualreviews.org/loi/biochem?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/0eea62e1f266f8b86ac52ade7ee3ceb70e9f62d2", + "title": "Structural aspects of the red cell anion exchange protein.", "abstract": + "PERSPECTIVES AND SUMMARy 512 STRUCTURE OF THE BAND 3 PROTEIN 513 Proteolytic + Cleavage Sites 513 Sequence ... , . . . . . . . . . . . . . . . . . . . . + . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . + . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 514 Chemical Modifications + 517 Topology oj Membrane Domain 519 Topology oJ Cytoplasmic Domain 523 POSTTRANSLATIONAL + MODIFICATIONS 523 Glycosylation . . . . . . . . . . . . . . . . . . . . . + . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . + . . . . . . . . . . . . . . . . . . . . . . . . . . . . 523 Phosphorylation + .. ........ 524 Methylation ....... . . ....... . .. . ....... . . , 524 BIOSYNTHESIS + AND ASSEMBLy 524", "venue": "Annual Review of Biochemistry", "year": 1986, + "referenceCount": 0, "citationCount": 125, "influentialCitationCount": 3, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["Review", "JournalArticle"], "publicationDate": null, "journal": {"volume": + "55", "pages": "\n 511-38\n ", "name": "Annual review of biochemistry"}, + "authors": [{"authorId": "4860515", "name": "D. Jay"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "1933bbfb32fa01db38664c8ae31531cda4db257d", + "externalIds": {"MAG": "2034431401", "DOI": "10.1111/j.1749-6632.1986.tb54426.x", + "CorpusId": 84367254}, "corpusId": 84367254, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/1933bbfb32fa01db38664c8ae31531cda4db257d", + "title": "Oncogenes and Phosphatidylinositol Turnover a", "abstract": "Products + of phosphatidylinositol turnover have recently been implicated as regulators + of cell growth and differentiation. Transformation of cells in culture by + infection with certain viruses (Rous sarcoma virus, Kirsten sarcoma virus, + and polyoma virus) or by transfection with the oncogenes carried by these + viruses affect the steady-state level of intermediates in the PI turnover + pathway. In addition, immunoprecipitates of the transforming gene products + of Rous sarcoma virus and polyoma virus contain activities of certain enzymes + in the PI turnover pathway. We have previously reported that polyoma middle + T immunoprecipitates can catalyze phosphorylation of PI to phosphatidylinositol-4-phosphate + (PIP). This activity is not intrinsic to middle T or c-src but is due to a + cellular enzyme that specifically associates with this complex. The PI kinase + is found in immunoprecipitates of the middle T protein from polyoma viruses + that are capable of cell transformation but does not associate with mutants + of middle T defective in transformation suggesting that this association may + be important for transformation.", "venue": "", "year": 1986, "referenceCount": + 26, "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": "1986-12-01", + "journal": {"volume": "488", "name": "Annals of the New York Academy of Sciences"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "79989587", + "name": "M. Whitman"}, {"authorId": "8044764", "name": "S. Chahwala"}, {"authorId": + "4459392", "name": "L. Fleischman"}, {"authorId": "32389352", "name": "D. + Kaplan"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": + "6665338", "name": "T. Roberts"}]}, {"paperId": "28b1a45babdcf7676c1fc78bef49e163888d0912", + "externalIds": {"MAG": "2467678472", "CorpusId": 29918419, "PubMed": "3019785"}, + "corpusId": 29918419, "publicationVenue": {"id": "c9cbc673-d571-425e-ad6e-edb23bb759e9", + "name": "Federation proceedings", "alternate_names": ["Fed proc"], "issn": + "0014-9446"}, "url": "https://www.semanticscholar.org/paper/28b1a45babdcf7676c1fc78bef49e163888d0912", + "title": "Phosphoinositide kinase activity and transformation.", "abstract": + "We have used the DNA tumor virus polyoma as a model system to examine whether + the phosphatidylinositol (PI) turnover pathway is a critical target for transforming + gene products. Polyoma-infected cells show elevated levels of polyphosphoinositides + and polyphosphoinositols, and a PI kinase activity is associated with middle + T antigen, a transforming gene product of polyoma virus. In anti-T immunoprecipitates + from polyoma-infected or -transformed cells, comparisons of wild-type and + polyoma mutants defective for transformation show a strong correlation between + middle T-associated PI kinase activity and transforming ability. Middle T + has previously been found to associate at the plasma membrane with pp60 c-src + and to activate it as a tyrosine kinase. c-src itself does not appear to phosphorylate + PI; however, the middle T/pp60 c-src tyrosine kinase activity may be important + for activation of PI kinase. Ammonium orthovanadate, a tyrosine phosphatase + inhibitor, elevates the middle T/pp60 c-src-associated PI kinase activity. + We propose that middle T/pp60 c-src activates a PI kinase and modulates PI + turnover in vivo by tyrosine phosphorylation.", "venue": "Federation proceedings", + "year": 1986, "referenceCount": 0, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1986-10-01", "journal": + {"volume": "45 11", "pages": "\n 2647-52\n ", "name": "Federation + proceedings"}, "authors": [{"authorId": "32113608", "name": "M. Whitman"}, + {"authorId": "32389352", "name": "D. Kaplan"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6665338", "name": "T. Roberts"}, {"authorId": + "4362128", "name": "B. Schaffhausen"}]}, {"paperId": "3daeb661d851e4d7bc4ffd92e125a48ccd485e64", + "externalIds": {"MAG": "1408723449", "DOI": "10.1016/S0070-2161(08)60733-9", + "CorpusId": 82727337}, "corpusId": 82727337, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/3daeb661d851e4d7bc4ffd92e125a48ccd485e64", + "title": "Chapter 11 B Lymphocyte Differentiation: Role of Phosphoinositides, + C Kinase, and Na+-H+ Exchange", "abstract": null, "venue": "", "year": 1986, + "referenceCount": 23, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + {"volume": "26", "pages": "193-199", "name": "Current topics in membranes + and transport"}, "authors": [{"authorId": "4078651", "name": "P. Rosoff"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "4e448176d72cf9f227c28af699be535e61c1cb94", + "externalIds": {"MAG": "1979715535", "DOI": "10.1016/0167-4889(86)90048-0", + "CorpusId": 33545013, "PubMed": "3013320"}, "corpusId": 33545013, "publicationVenue": + {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", "name": "Biochimica et Biophysica + Acta", "type": "journal", "alternate_names": ["Biochim Biophys Acta"], "issn": + "0006-3002", "alternate_issns": ["1878-2434"], "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/4e448176d72cf9f227c28af699be535e61c1cb94", + "title": "Protein kinase C of human erythrocytes phosphorylates bands 4.1 + and 4.9.", "abstract": null, "venue": "Biochimica et Biophysica Acta", "year": + 1986, "referenceCount": 33, "citationCount": 20, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1986-07-11", "journal": {"volume": "887 2", "pages": "\n 142-9\n ", + "name": "Biochimica et biophysica acta"}, "authors": [{"authorId": "5052888", + "name": "W. Faquin"}, {"authorId": "8044764", "name": "S. Chahwala"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "6913699", "name": "D. Branton"}]}, + {"paperId": "50655e6df66bdbb388459e8c52b64949466af1f0", "externalIds": {"MAG": + "2396781587", "CorpusId": 24113374, "PubMed": "2827283"}, "corpusId": 24113374, + "publicationVenue": {"id": "8dd9c381-1194-487b-b007-8aa1dfe260f4", "name": + "Symposium on Fundamental Cancer Research", "alternate_names": ["Symp Fundam + Cancer Res"], "issn": "0190-1214"}, "url": "https://www.semanticscholar.org/paper/50655e6df66bdbb388459e8c52b64949466af1f0", + "title": "Phosphatidylinositol kinases and cell transformation.", "abstract": + "Products of phosphatidylinositol (PI) turnover have recently been implicated + as regulators of cell growth and differentiation. Transformation of cells + in culture by infection with certain viruses (Rous sarcoma virus, Kirsten + sarcoma virus, and polyoma virus) or by transfection with the oncogenes carried + by these viruses affect the steady-state level of intermediates in the PI + turnover pathway. In addition, immunoprecipitates of the transforming gene + products of Rous sarcoma virus and polyoma virus contain activities of certain + enzymes in the PI turnover pathway. We have previously reported that polyoma + middle T immunoprecipitates can catalyze phosphorylation of PI to phosphatidylinositol-4-phosphate + (PIP). This activity is not intrinsic to middle T or pp60c-src but is due + to a cellular enzyme that specifically associates with the middle T/pp60c-src + complex. The PI kinase is found in immunoprecipitates of the middle t protein + from polyoma viruses that are capable of cell transformation but does not + associate with mutants of middle t defective in transformation, suggesting + that this association may be important for transformation. Two PI kinases + from fibroblasts (type I and type II) that are separable by anion exchange + chromatography have been partially purified and characterized. These enzymes + differ in their Km for ATP as well as their Ki for adenosine and ADP. Only + the type I PI kinase specifically associates with the transformation-competent + mutants of middle T.", "venue": "Symposium on Fundamental Cancer Research", + "year": 1986, "referenceCount": 0, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], "publicationDate": + null, "journal": {"volume": "39", "pages": "\n 165-72\n ", + "name": "Symposium on Fundamental Cancer Research"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "32113608", "name": "M. Whitman"}, + {"authorId": "32389352", "name": "D. Kaplan"}, {"authorId": "8044764", "name": + "S. Chahwala"}, {"authorId": "4459392", "name": "L. Fleischman"}, {"authorId": + "10330714", "name": "G. Endemann"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, + {"authorId": "6665338", "name": "T. Roberts"}]}, {"paperId": "870784461424be9a388da21961018326ced401f1", + "externalIds": {"DOI": "10.1111/j.1749-6632.1986.tb46580.x", "CorpusId": 25171573, + "PubMed": "2437850"}, "corpusId": 25171573, "publicationVenue": {"id": "fa1f0815-0811-4291-b4fc-8230a6c9bf5b", + "name": "Annals of the New York Academy of Sciences", "type": "journal", "alternate_names": + ["Ann n y Acad Sci"], "issn": "0077-8923", "url": "http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1749-6632", + "alternate_urls": ["http://www.annalsnyas.org/", "http://www.nyas.org/publications/annals/default.aspx", + "https://onlinelibrary.wiley.com/journal/17496632"]}, "url": "https://www.semanticscholar.org/paper/870784461424be9a388da21961018326ced401f1", + "title": "Oncogenes and phosphatidylinositol turnover.", "abstract": "Products + of phosphatidylinositol turnover have recently been implicated as regulators + of cell growth and differentiation. Transformation of cells in culture by + infection with certain viruses (Rous sarcoma virus, Kirsten sarcoma virus, + and polyoma virus) or by transfection with the oncogenes carried by these + viruses affect the steady-state level of intermediates in the PI turnover + pathway. In addition, immunoprecipitates of the transforming gene products + of Rous sarcoma virus and polyoma virus contain activities of certain enzymes + in the PI turnover pathway. We have previously reported that polyoma middle + T immunoprecipitates can catalyze phosphorylation of PI to phosphatidylinositol-4-phosphate + (PIP). This activity is not intrinsic to middle T or c-src but is due to a + cellular enzyme that specifically associates with this complex. The PI kinase + is found in immunoprecipitates of the middle T protein from polyoma viruses + that are capable of cell transformation but does not associate with mutants + of middle T defective in transformation suggesting that this association may + be important for transformation.", "venue": "Annals of the New York Academy + of Sciences", "year": 1986, "referenceCount": 0, "citationCount": 7, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine"], + "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": null, "journal": {"volume": "488", "pages": "\n 481-90\n ", + "name": "Annals of the New York Academy of Sciences"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "32113608", "name": "M. Whitman"}, + {"authorId": "8044764", "name": "S. Chahwala"}, {"authorId": "4459392", "name": + "L. Fleischman"}, {"authorId": "32389352", "name": "D. Kaplan"}, {"authorId": + "4362128", "name": "B. Schaffhausen"}, {"authorId": "6665338", "name": "T. + Roberts"}]}, {"paperId": "b3e5245b9784a5fbff52a1570469ab75f8bdbdd3", "externalIds": + {"MAG": "2036744157", "DOI": "10.1126/SCIENCE.3001936", "CorpusId": 44327583, + "PubMed": "3001936"}, "corpusId": 44327583, "publicationVenue": {"id": "f59506a8-d8bb-4101-b3d4-c4ac3ed03dad", + "name": "Science", "type": "journal", "issn": "0193-4511", "alternate_issns": + ["0036-8075"], "url": "https://www.jstor.org/journal/science", "alternate_urls": + ["https://www.sciencemag.org/", "http://www.sciencemag.org/", "http://www.jstor.org/journals/00368075.html", + "http://www.sciencemag.org/archive/"]}, "url": "https://www.semanticscholar.org/paper/b3e5245b9784a5fbff52a1570469ab75f8bdbdd3", + "title": "ras-transformed cells: altered levels of phosphatidylinositol-4,5-bisphosphate + and catabolites.", "abstract": "Steady-state cellular levels of phosphatidylinositol-4,5-bisphosphate + (PIP2), 1,2-diacylglycerol (DAG), and inositol phosphates have been measured + in two different fibroblast cell lines (NIH 3T3 and NRK cells) before and + after transformation with three different ras genes. At high cell density + the ratio of DAG to PIP2 was 2.5- to 3-fold higher in the ras-transformed + cells than in their untransformed counterparts. The sum of the water-soluble + breakdown products of the polyphosphoinositides, inositol-1,4-bisphosphate + and inositol-1,4,5-trisphosphate, was also elevated in ras-transformed NRK + cells compared with nontransformed NRK cells. These findings suggest that + the ras (p21) protein may act by affecting these levels, possibly as a regulatory + element in the PIP2 breakdown pathway.", "venue": "Science", "year": 1986, + "referenceCount": 53, "citationCount": 367, "influentialCitationCount": 4, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1986-01-24", "journal": {"volume": "231 4736", "pages": "\n 407-10\n ", + "name": "Science"}, "authors": [{"authorId": "4459392", "name": "L. Fleischman"}, + {"authorId": "8044764", "name": "S. Chahwala"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "d9e6538d636f195d4bb8b6c4942f2fe7bce9d10a", "externalIds": + {"MAG": "57097630", "DOI": "10.1007/978-1-4684-5062-0_12", "CorpusId": 81108690}, + "corpusId": 81108690, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d9e6538d636f195d4bb8b6c4942f2fe7bce9d10a", + "title": "Comparison of the Na+ Pump and the Ouabain-Resistant K+ Transport + System with Other Metal Ion Transport ATPases", "abstract": null, "venue": + "", "year": 1986, "referenceCount": 32, "citationCount": 1, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + null, "journal": {"volume": "", "pages": "249-259", "name": ""}, "authors": + [{"authorId": "34784769", "name": "L. English"}, {"authorId": "33469167", + "name": "B. White"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "ddf80e3bda0cd0f5fa91378bf34f02b26f42228b", "externalIds": {"MAG": "2065447875", + "DOI": "10.1073/PNAS.83.11.3624", "CorpusId": 40508765, "PubMed": "2424008"}, + "corpusId": 40508765, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/ddf80e3bda0cd0f5fa91378bf34f02b26f42228b", + "title": "Phosphatidylinositol metabolism and polyoma-mediated transformation.", + "abstract": "The effect of polyoma middle-sized tumor antigen (MTAg) on phosphatidylinositol + metabolism has been characterized in vivo and in vitro using polyoma-transformed + and polyoma-infected cells. Cells infected with transformation-competent polyoma + virus exhibit increased levels of inositol phospholipids and the second messenger + inositol trisphosphate. MTAg or pp60c-src immunoprecipitates from MTAg-transformed + cells contain an activity that phosphorylates phosphatidylinositol and phosphatidylinositol + 4-phosphate. This activity is induced in parallel with MTAg when the MTAg + synthesis is regulated by hormonal or heavy metal inducers. Immunoprecipitates + from one class of polyoma mutants defective in transformation have a reduced + level of associated phosphatidylinositol kinase activity in vitro yet are + capable of tyrosine phosphorylation on exogenous protein substrates at rates + comparable to wild-type virus. Thus, for these mutants, phosphatidylinositol + kinase activity is more tightly correlated with transformation than is protein + kinase activity. These results suggest that alterations in phosphatidylinositol + metabolism by MTAg play a role in transformation by polyoma virus.", "venue": + "Proceedings of the National Academy of Sciences of the United States of America", + "year": 1986, "referenceCount": 0, "citationCount": 168, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://europepmc.org/articles/pmc323575?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1986-06-01", "journal": {"volume": + "83 11", "pages": "\n 3624-8\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "32389352", "name": "D. Kaplan"}, {"authorId": "32113608", "name": + "M. Whitman"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, {"authorId": + "77741236", "name": "L. Raptis"}, {"authorId": "5539122", "name": "R. Garcea"}, + {"authorId": "1958759811", "name": "D. Pallas"}, {"authorId": "6665338", "name": + "T. Roberts"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "093ac1569ef5833ababe3e30fb198ef2a48706c9", "externalIds": {"MAG": "2090940799", + "DOI": "10.1038/315239A0", "CorpusId": 4337999, "PubMed": "2987699"}, "corpusId": + 4337999, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/093ac1569ef5833ababe3e30fb198ef2a48706c9", + "title": "Association of phosphatidylinositol kinase activity with polyoma + middle-T competent for transformation", "abstract": null, "venue": "Nature", + "year": 1985, "referenceCount": 27, "citationCount": 696, "influentialCitationCount": + 15, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1985-05-16", "journal": {"volume": "315", "pages": "239-242", "name": "Nature"}, + "authors": [{"authorId": "32113608", "name": "M. Whitman"}, {"authorId": "32389352", + "name": "D. Kaplan"}, {"authorId": "4362128", "name": "B. Schaffhausen"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "6665338", "name": + "T. Roberts"}]}, {"paperId": "42d5440c808ed4397b5f66d61bdbfd03bbeb4eb9", "externalIds": + {"MAG": "1507900720", "CorpusId": 31043389, "PubMed": "2981832"}, "corpusId": + 31043389, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/42d5440c808ed4397b5f66d61bdbfd03bbeb4eb9", + "title": "Expression of an ouabain resistance gene in transfected cells. Ouabain + treatment induces a K+-transport system.", "abstract": "We have investigated + the expression of a cloned mouse gene which confers ouabain resistance to + African green monkey kidney (CV1) cells. CV1 cells carrying the transfected + ouabain resistance (ouaR) gene express an ouabain-inducible K+-transport system. + This K+-transport system is not a normal (Na,K)-ATPase since plasma membranes + prepared from the transfected cells have significantly reduced Na+-stimulated + ATPase activity. RNA sequences homologous to the transfected gene are observed + in abundance only following exposure of transfectants to ouabain. The small + size of the message induced (1.2 kilobases) also argues that the gene does + not code for the alpha-subunit of the (Na,K)-ATPase. Ouabain-treated transfected + cells maintain an internal [K+] of 113 mM; a level close to the 139 mM of + control cells. However, ouabain-treated transfectants exhibit an internal + [Na+] of 61 mM, which is 3-6 times the level in untreated cells (11-21 mM). + These results suggest: ouabain resistance can be conferred by a gene which + codes for an ouabain-inducible K+-transport system; induction of this transport + system by ouabain is due to increased levels of mRNA coded for by the ouabain + resistance gene; and the ouabain resistance gene does not encode for the alpha-subunit + of the (Na,K)-ATPase.", "venue": "Journal of Biological Chemistry", "year": + 1985, "referenceCount": 0, "citationCount": 22, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1985-01-25", "journal": {"volume": "260 2", "pages": "\n 1114-9\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "34784769", + "name": "L. English"}, {"authorId": "48381149", "name": "J. Epstein"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "10127476", "name": "D. Housman"}, + {"authorId": "144579743", "name": "R. Levenson"}]}, {"paperId": "43749da62aab459c50dc1422c5deaf4e03bd3ae7", + "externalIds": {"MAG": "2185507322", "CorpusId": 23876147, "PubMed": "2981828"}, + "corpusId": 23876147, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/43749da62aab459c50dc1422c5deaf4e03bd3ae7", + "title": "Hypothalamic factor inhibits the (Na,K)ATPase from the extracellular + surface. Mechanism of inhibition.", "abstract": "We have characterized the + effect of a stable small molecule isolated from bovine hypothalamus (Haupert, + G. T., and Sancho, J. M. (1979) Proc. Natl. Acad. Sci. 76, 4658-4660) on mammalian + (Na,K)ATPase. This hypothalamus-derived inhibitory factor, HIF, has been shown + to inhibit ATPase activity of purified dog kidney enzyme reversibly with high + affinity (Haupert, G. T., Carilli, C. T., and Cantley, L. C. (1984) Am. J. + Physiol. 247, F919-F924). In this report it is shown that HIF inhibits the + ouabain sensitive component of 86Rb+ uptake into human red blood cells. HIF + also inhibited (Na,K)ATPase activity of unsealed red cell membranes but not + that of sealed inside-out vesicles, indicating that HIF is impermeant to red + cell membranes and inhibits the (Na,K)ATPase from the extracellular side. + In unsealed human red cell membranes, concentrations of HIF which caused 70% + inhibition of the (Na,K)ATPase did not inhibit ATP hydrolysis by plasma membrane + (Ca2+)ATPase or (Mg2+)ATPase. However, at a similar concentration, HIF was + shown to inhibit rabbit muscle sarcoplasmic reticulum (Ca2+)ATPase. HIF also + inhibited p-nitrophenylphosphatase activity of unmodified or fluorescein-5''-iso-thiocyanate + labeled dog kidney (Na,K)ATPase. As judged by fluorescein fluorescence of + the modified enzyme, HIF stabilized the low fluorescent \"E2\" conformation + of the enzyme similar to that stabilized by ouabain. However, unlike ouabain, + HIF blocked covalent phosphorylation of dog kidney (Na,K)ATPase by inorganic + phosphate. These studies show that HIF is an inhibitor of (Na,K)ATPase which + acts from the extracellular side of the membrane by a mechanism similar to + but not identical to that of cardiac glycosides.", "venue": "Journal of Biological + Chemistry", "year": 1985, "referenceCount": 0, "citationCount": 56, "influentialCitationCount": + 2, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1985-01-25", "journal": {"volume": + "260 2", "pages": "\n 1027-31\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "2060790666", "name": "C. + Carilli"}, {"authorId": "40289180", "name": "M. Berne"}, {"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "6466373", "name": "G. T. Haupert"}]}, + {"paperId": "8aed6016a5f08f28a308166e557b2d32bdfb11a7", "externalIds": {"MAG": + "2412355881", "CorpusId": 11472520, "PubMed": "2996016"}, "corpusId": 11472520, + "publicationVenue": {"id": "736e8a50-08e5-4fdf-a56c-1288eae28f3c", "name": + "Progress in clinical and biological research", "type": "journal", "alternate_names": + ["Progress in Clinical and Biological Research", "Prog Clin Biological Res", + "Prog clin biological res"], "issn": "0361-7742"}, "url": "https://www.semanticscholar.org/paper/8aed6016a5f08f28a308166e557b2d32bdfb11a7", + "title": "The role of ion fluxes in hematopoietic cell differentiation.", + "abstract": null, "venue": "Progress in clinical and biological research", + "year": 1985, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + null, "journal": {"volume": "184", "pages": "\n 331-9\n ", + "name": "Progress in clinical and biological research"}, "authors": [{"authorId": + "4078651", "name": "P. Rosoff"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "9656af04e36107ac2516b775151125166d9c3b85", "externalIds": {"MAG": + "1603620343", "DOI": "10.1016/s0021-9258(17)38683-0", "CorpusId": 6202775, + "PubMed": "2997191"}, "corpusId": 6202775, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/9656af04e36107ac2516b775151125166d9c3b85", + "title": "Stimulation of the T3-T cell receptor-associated Ca2+ influx enhances + the activity of the Na+/H+ exchanger in a leukemic human T cell line.", "abstract": + null, "venue": "Journal of Biological Chemistry", "year": 1985, "referenceCount": + 2, "citationCount": 65, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1985-11-15", "journal": + {"volume": "260 26", "pages": "\n 14053-9\n ", "name": "The + Journal of biological chemistry"}, "authors": [{"authorId": "4078651", "name": + "P. Rosoff"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "a4821cc4667211847f23810a3f7dafdc368027ed", "externalIds": {"MAG": "1509406829", + "DOI": "10.1016/s0021-9258(17)39354-7", "CorpusId": 36602004, "PubMed": "3874870"}, + "corpusId": 36602004, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/a4821cc4667211847f23810a3f7dafdc368027ed", + "title": "Lipopolysaccharide and phorbol esters induce differentiation but + have opposite effects on phosphatidylinositol turnover and Ca2+ mobilization + in 70Z/3 pre-B lymphocytes.", "abstract": null, "venue": "Journal of Biological + Chemistry", "year": 1985, "referenceCount": 0, "citationCount": 106, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Computer Science", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1985-08-05", "journal": + {"volume": "260 16", "pages": "\n 9209-15\n ", "name": "The + Journal of biological chemistry"}, "authors": [{"authorId": "4078651", "name": + "P. Rosoff"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "c25f85524acff9fe905be75c28da2979d78cc5b2", "externalIds": {"MAG": "106263185", + "CorpusId": 39958523, "PubMed": "2984780"}, "corpusId": 39958523, "publicationVenue": + {"id": "15ff847f-6fb7-4298-88a5-9604bbd7baec", "name": "Society of General + Physiologists series", "type": "journal", "alternate_names": ["Soc Gen Physiol + ser"], "issn": "0094-7733"}, "url": "https://www.semanticscholar.org/paper/c25f85524acff9fe905be75c28da2979d78cc5b2", + "title": "Ion fluxes and differentiation in transformed cell lines.", "abstract": + null, "venue": "Society of General Physiologists series", "year": 1985, "referenceCount": + 0, "citationCount": 6, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}], "publicationTypes": ["Review", "JournalArticle"], + "publicationDate": null, "journal": {"volume": "39", "pages": "\n 193-204\n ", + "name": "Society of General Physiologists series"}, "authors": [{"authorId": + "4078651", "name": "P. Rosoff"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "df8e7cf49fc5eeb55b7286cf4aeecc1f3a35466c", "externalIds": {"MAG": + "2243707934", "DOI": "10.1007/978-1-4613-2377-8_20", "CorpusId": 101149200}, + "corpusId": 101149200, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/df8e7cf49fc5eeb55b7286cf4aeecc1f3a35466c", + "title": "Na+ and Ca2+ Fluxes and Differentiation of Transformed Cells", "abstract": + null, "venue": "", "year": 1985, "referenceCount": 20, "citationCount": 0, + "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": null, + "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "", + "pages": "173-178", "name": ""}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4078651", "name": "P. Rosoff"}, {"authorId": + "144579743", "name": "R. Levenson"}, {"authorId": "5583964", "name": "I. Macara"}, + {"authorId": "34912412", "name": "L. Yeh"}, {"authorId": "50678030", "name": + "L. Ling"}, {"authorId": "34784769", "name": "L. English"}]}, {"paperId": + "f74e8f673b4b1f9ed804f34af9b5b2ee96c4ab2b", "externalIds": {"MAG": "2054320393", + "DOI": "10.1016/0092-8674(85)90206-5", "CorpusId": 38617826, "PubMed": "2578888"}, + "corpusId": 38617826, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/f74e8f673b4b1f9ed804f34af9b5b2ee96c4ab2b", + "title": "Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive + calcium influx", "abstract": null, "venue": "Cell", "year": 1985, "referenceCount": + 57, "citationCount": 238, "influentialCitationCount": 1, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Medicine", "Biology"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1985-03-01", "journal": {"volume": + "40", "pages": "583-590", "name": "Cell"}, "authors": [{"authorId": "12579610", + "name": "H. Oettgen"}, {"authorId": "4658870", "name": "C. Terhorst"}, {"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "4078651", "name": "P. Rosoff"}]}, + {"paperId": "4917b16b5e37b0538c3efbad7bf0458523e11235", "externalIds": {"MAG": + "183187594", "DOI": "10.1152/AJPRENAL.1984.247.6.F919", "CorpusId": 32623618, + "PubMed": "6095682"}, "corpusId": 32623618, "publicationVenue": {"id": "998813ea-da72-494a-90fc-783751929f3c", + "name": "American Journal of Physiology", "type": "journal", "alternate_names": + ["Am J Physiol"], "issn": "0002-9513", "alternate_issns": ["2163-5773"], "url": + "http://search.epnet.com/direct.asp?db=aph&jid=AHY", "alternate_urls": ["http://www.physiology.org/", + "http://www.physiology.org/journal/ajplegacy", "https://www.physiology.org/journal/ajpcell", + "http://ajpcon.physiology.org/", "https://www.biodiversitylibrary.org/bibliography/38917"]}, + "url": "https://www.semanticscholar.org/paper/4917b16b5e37b0538c3efbad7bf0458523e11235", + "title": "Hypothalamic sodium-transport inhibitor is a high-affinity reversible + inhibitor of Na+-K+-ATPase.", "abstract": "Bovine hypothalamus contains a + stable, low molecular weight substance with ouabain-like properties. To further + study its mechanism of action and potential physiological importance we examined + its effects on purified Na+-K+-ATPase in a kinetic coupled-enzyme assay. Under + optimal conditions up to 95% of Na+-K+-ATPase activity could be inhibited + by the factor. Mg2+ is required for maximal inhibitory activity, but ligand + requirements for optimal activity are otherwise distinct from those of both + ouabain and vanadate. Inhibition is reversed by high concentrations of sodium + chloride plus EDTA. Kinetic analysis yielded a Ki = 1.4 nM. The hypothalamic + factor is a high-affinity reversible inhibitor of Na+-K+-ATPase, being at + least as potent as the cardiac glycoside ouabain and may be a circulating + inhibitor of sodium transport, which appears to be associated with experimental + volume-expanded hypertension and human essential hypertension.", "venue": + "American Journal of Physiology", "year": 1984, "referenceCount": 0, "citationCount": + 50, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1984-12-01", "journal": {"volume": "247 6 Pt 2", "pages": "\n F919-24\n ", + "name": "The American journal of physiology"}, "authors": [{"authorId": "6466373", + "name": "G. T. Haupert"}, {"authorId": "2060790666", "name": "C. Carilli"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "68e6babe5546eb91d99134e348e1afc7ec292e1e", + "externalIds": {"MAG": "1971333358", "DOI": "10.1073/PNAS.81.7.2117", "CorpusId": + 22275277, "PubMed": "6326105"}, "corpusId": 22275277, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/68e6babe5546eb91d99134e348e1afc7ec292e1e", + "title": "Evidence that the Rous sarcoma virus transforming gene product phosphorylates + phosphatidylinositol and diacylglycerol.", "abstract": "The ability of purified + Rous sarcoma virus transforming gene product, pp60v-src, to phosphorylate + phosphatidylinositol and diacylglycerol was investigated. Phosphatidylinositol + was phosphorylated to form both mono- and diphosphorylated derivatives. 1,2-Diacylglycerol + was phosphorylated to form phosphatidic acid. These activities showed the + same thermolability and the same sensitivity to inhibitors as shown by the + casein kinase activity of pp60v-src. In addition, when serum-starved chicken + embryo fibroblasts transformed by a virus mutant temperature-sensitive for + transformation were shifted from the nonpermissive to permissive temperature, + an increase of 50-100% in the labeling of phosphatidylinositol 4-phosphate, + phosphatidylinositol 4,5-bisphosphate, and phosphatidic acid was observed, + as compared to uninfected cells.", "venue": "Proceedings of the National Academy + of Sciences of the United States of America", "year": 1984, "referenceCount": + 1, "citationCount": 357, "influentialCitationCount": 4, "isOpenAccess": true, + "openAccessPdf": {"url": "http://www.pnas.org/content/81/7/2117.full.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Computer Science", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1984-04-01", "journal": {"volume": "81 7", "pages": "\n 2117-21\n ", + "name": "Proceedings of the National Academy of Sciences of the United States + of America"}, "authors": [{"authorId": "2052521806", "name": "Y. Sugimoto"}, + {"authorId": "39063562", "name": "M. Whitman"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "6286526", "name": "R. Erikson"}]}, {"paperId": + "8110a2ca685475b976654d14d4a0ca50321add66", "externalIds": {"MAG": "1585242164", + "DOI": "10.1016/s0021-9258(17)39836-8", "CorpusId": 7721367, "PubMed": "6144681"}, + "corpusId": 7721367, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/8110a2ca685475b976654d14d4a0ca50321add66", + "title": "Phorbol esters induce differentiation in a pre-B-lymphocyte cell + line by enhancing Na+/H+ exchange.", "abstract": null, "venue": "Journal of + Biological Chemistry", "year": 1984, "referenceCount": 1, "citationCount": + 147, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1984-06-10", "journal": {"volume": "259 11", "pages": + "\n 7056-60\n ", "name": "The Journal of biological chemistry"}, + "authors": [{"authorId": "4078651", "name": "P. Rosoff"}, {"authorId": "87374149", + "name": "L. Stein"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "be525f6f4cb36e8dcb6c58b2e4da2d88b3200a63", "externalIds": {"MAG": "1580187066", + "DOI": "10.1016/s0021-9258(17)39699-0", "CorpusId": 44937037, "PubMed": "6145711"}, + "corpusId": 44937037, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/be525f6f4cb36e8dcb6c58b2e4da2d88b3200a63", + "title": "Characterization of the ATP-dependent proton pump of clathrin-coated + vesicles.", "abstract": null, "venue": "Journal of Biological Chemistry", + "year": 1984, "referenceCount": 0, "citationCount": 41, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1984-07-10", "journal": {"volume": "259 13", "pages": "\n 8101-5\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "145289081", + "name": "M. Forgac"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d7638f17c6bcf162c56a6a1d4670c48399989a05", "externalIds": {"MAG": "1574702655", + "CorpusId": 25502233, "PubMed": "6594338"}, "corpusId": 25502233, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/d7638f17c6bcf162c56a6a1d4670c48399989a05", + "title": "Extracellular ATP induces ion fluxes and inhibits growth of Friend + erythroleukemia cells.", "abstract": "Extracellular ATP (1 mM) inhibited the + growth of Friend virus-infected murine erythroleukemia cells (MEL cells) but + had no effect on dimethyl sulfoxide-induced differentiation. ATP (1 mM) also + caused changes in the permeability of MEL cells to ions. There was an increased + influx of 45Ca2+ from a basal level of 5 pmol/min to 18 pmol/min/10(6) cells + to achieve a 2-fold increase in steady-state Ca2+ as measured at isotopic + equilibration. Ca2+ influx was blocked by diisothiocyanostilbene disulfonate + (DIDS), an inhibitor of anion transport. ATP also stimulated Cl- uptake, and + this flux was inhibited by DIDS. The ratio of ATP stimulated Cl- to Ca2+ uptake + was 1.6:1. K+ and Na+ influx were also stimulated by ATP, but phosphate uptake + was inhibited; the Na+ influx dissipated the Na+ gradient and thus inhibited + nutrient uptake. ATP-stimulated K+ influx was ouabain inhibitable; however, + the total cellular K+ decreased due to an ATP-stimulated ouabain-resistant + K+ efflux. Na+ influx and Ca2+ influx occurred by separate independent routes, + since Na+ influx was not inhibited by DIDS. The effects observed were specific + for ATP *K1/2 MgATP = 0.7 mM) since AMP, GTP, adenosine, and the slowly hydrolyzable + ATP analogue adenyl-5''-yl imidodiphosphate were without effect. The major + ionic changes in the cell were a decrease in K+ and increase in Na+; cytoplasmic + pH and free Ca2+ did not change appreciably. These ATP-induced changes in + ion flux are considered to be responsible for growth inhibition.", "venue": + "Journal of Biological Chemistry", "year": 1984, "referenceCount": 2, "citationCount": + 71, "influentialCitationCount": 3, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1984-11-25", "journal": {"volume": "259 22", "pages": + "\n 13717-22\n ", "name": "The Journal of biological chemistry"}, + "authors": [{"authorId": "8044764", "name": "S. Chahwala"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "e2ff03903fb47314482c2603f926f7cd5265f63d", + "externalIds": {"MAG": "2090761406", "DOI": "10.1002/JCP.1041210115", "CorpusId": + 22010992, "PubMed": "6480706"}, "corpusId": 22010992, "publicationVenue": + {"id": "cdf4bb1c-e624-482e-8289-da2009c4c31a", "name": "Journal of Cellular + Physiology", "type": "journal", "alternate_names": ["J Cell Physiol"], "issn": + "0021-9541", "url": "http://eu.wiley.com/WileyCDA/WileyTitle/productCd-JCP.html", + "alternate_urls": ["http://www3.interscience.wiley.com/cgi-bin/jhome/109898032", + "http://onlinelibrary.wiley.com/journal/10.1002/%28issn%291097-4652", "http://onlinelibrary.wiley.com/journal/10.1002/(issn)1097-4652", + "https://onlinelibrary.wiley.com/journal/10974652", "http://www3.interscience.wiley.com/cgi-bin/jhome/31010"]}, + "url": "https://www.semanticscholar.org/paper/e2ff03903fb47314482c2603f926f7cd5265f63d", + "title": "Characterization of monovalent ion transport systems in an insect + cell line (Manduca sexta embryonic cell line che)", "abstract": "The monovalent + ion transport systems of an immortalized insect cell line (CHE) have been + investigated. These cells are unusual in that unlike most vertebrate cells, + their normal extracellular environment consists of high potassium and low + sodium concentrations. CHE cells maintained high intracellular [K+] through + both a furosemide\u2010inhibitable and a vanadate\u2010inhibitable transport + system. Intracellular exchangeable [Na+] was slightly lower than the extracellular + [Na+] and was maintained at this level through a vanadate\u2010sensitive transport + system. Na+ uptake was also inhibited by furosemide: however, the stoichiometry + of furosemide\u2010sensitive Na+ uptake when compared with furosemide\u2010sensitive + K+ uptake indicated that these cations are not cotransported. 4,4\u2032\u2010Diisothiocyano\u20102,2\u2032\u2010disulfonic + acid stilbene (DIDS) inhibited Na+, K+, and Cl\u2212 uptake. Vanadate and + furosemide decreased cytoplasmimic pH, while cytoplasmic pH increased in the + presence of DIDS. A model is presented explaining how Na+, K+, Cl\u2212, H+ + and HCO3 \u2212 fluxes are regulated in these cells.", "venue": "Journal of + Cellular Physiology", "year": 1984, "referenceCount": 30, "citationCount": + 19, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], + "publicationDate": "1984-10-01", "journal": {"volume": "121", "name": "Journal + of Cellular Physiology"}, "authors": [{"authorId": "34784769", "name": "L. + English"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "1ca4e503c84fc64ffb789f5033ea4e049538e89a", + "externalIds": {"MAG": "1185978304", "DOI": "10.1016/S0070-2161(08)60564-X", + "CorpusId": 82338418}, "corpusId": 82338418, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/1ca4e503c84fc64ffb789f5033ea4e049538e89a", + "title": "The Active Site Structure of Na,K-ATPase: Location of a Specific + Fluorescein Isothiocyanate-Reactive Site", "abstract": null, "venue": "", + "year": 1983, "referenceCount": 4, "citationCount": 3, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + {"volume": "19", "pages": "149-151", "name": "Current topics in membranes + and transport"}, "authors": [{"authorId": "2060790666", "name": "C. Carilli"}, + {"authorId": "2284479", "name": "R. Farley"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "3198c7f92cd7bc3b6d6099d5cefed911304cd82c", "externalIds": + {"MAG": "2197834256", "DOI": "10.1016/S0070-2161(08)60637-1", "CorpusId": + 86259996}, "corpusId": 86259996, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/3198c7f92cd7bc3b6d6099d5cefed911304cd82c", + "title": "Role of Na+ andCa2+ Fluxes in Terminal Differentiation of Murine + Erythroleukemia Cells", "abstract": null, "venue": "", "year": 1983, "referenceCount": + 8, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": [{"category": + "Biology", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "19", + "pages": "797-802", "name": "Current topics in membranes and transport"}, + "authors": [{"authorId": "5583964", "name": "I. Macara"}, {"authorId": "29327352", + "name": "R. Smith"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "3d2a4cafcf11e90cd15f2bfd445543044a1e174a", "externalIds": {"MAG": "2053803291", + "DOI": "10.1073/PNAS.80.24.7547", "CorpusId": 38391710, "PubMed": "6608724"}, + "corpusId": 38391710, "publicationVenue": {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", + "name": "Proceedings of the National Academy of Sciences of the United States + of America", "type": "journal", "alternate_names": ["Proc National Acad Sci + u s Am"], "issn": "0027-8424", "url": "https://www.jstor.org/journal/procnatiacadscie", + "alternate_urls": ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", + "http://www.pnas.org/"]}, "url": "https://www.semanticscholar.org/paper/3d2a4cafcf11e90cd15f2bfd445543044a1e174a", + "title": "Increasing the intracellular Na+ concentration induces differentiation + in a pre-B lymphocyte cell line.", "abstract": "The ability of lipopolysaccharide + (LPS), a polyclonal B-cell mitogen, to induce differentiation in the pre-B + cell tumor line 70Z/3 can be mimicked by drugs that increase the intracellular + Na+ concentration. Pharmacologically increasing the cellular Na+ content with + monensin, a sodium ionophore, or ouabain, a specific inhibitor of Na+, K+-ATPase, + induces surface IgM expression in these cells. We have shown that LPS stimulates + uptake of Na+ through an amiloride-sensitive pathway. These results show that + the essential action of LPS to induce surface IgM expression is activation + of a Na+ uptake system.", "venue": "Proceedings of the National Academy of + Sciences of the United States of America", "year": 1983, "referenceCount": + 1, "citationCount": 56, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc389989?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1983-12-01", "journal": {"volume": + "80 24", "pages": "\n 7547-50\n ", "name": "Proceedings of + the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "4078651", "name": "P. Rosoff"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "4946a3ab3de02737180767f925ea67f8f67e17ec", "externalIds": + {"MAG": "1501557066", "DOI": "10.1016/s0021-9258(18)33056-4", "CorpusId": + 33811079, "PubMed": "6185490"}, "corpusId": 33811079, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/4946a3ab3de02737180767f925ea67f8f67e17ec", + "title": "Evidence that inhibitors of anion exchange induce a transmembrane + conformational change in band 3.", "abstract": null, "venue": "Journal of + Biological Chemistry", "year": 1983, "referenceCount": 1, "citationCount": + 48, "influentialCitationCount": 2, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1983-02-10", "journal": {"volume": "258 3", "pages": "\n 1785-92\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "5583964", + "name": "I. Macara"}, {"authorId": "2056251182", "name": "S. Kuo"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "6454c578d54c0d7e94ee061c205fe8ccb21146ae", + "externalIds": {"MAG": "2083822287", "PubMedCentral": "2112600", "DOI": "10.1083/JCB.97.4.1299", + "CorpusId": 84974704, "PubMed": "6311842"}, "corpusId": 84974704, "publicationVenue": + {"id": "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/6454c578d54c0d7e94ee061c205fe8ccb21146ae", + "title": "Vanadium stimulates the (Na+,K+) pump in friend erythroleukemia + cells and blocks erythropoiesis", "abstract": "Friend murine erythroleukemia + cells underwent apparently normal erythropoiesis when treated with dimethyl + sulfoxide. One of the earliest events associated with this induction was a + decrease in ouabain sensitive 86Rb+ uptake, an assay of the plasma membrane + Na,K(ATPase). Ammonium vanadate (10 microM) blocked differentiation of these + cells without affecting cell viability. Vanadium was taken up by Friend cells + and prevented the dimethyl sulfoxide-induced decrease in ouabain sensitive + 86Rb+ uptake. Vanadate reactivated 86Rb+ transport previously inhibited by + dimethyl sulfoxide treatment but had no affect on 86Rb+ transport in untreated + cells. These results suggest an essential role for the (Na,K)ATPase in cell + differentiation.", "venue": "Journal of Cell Biology", "year": 1983, "referenceCount": + 21, "citationCount": 30, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc2112600?pdf=render", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}, {"category": + "Medicine", "source": "s2-fos-model"}, {"category": "Chemistry", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1983-10-01", "journal": {"volume": "97", "pages": "1299 - 1302", "name": + "The Journal of Cell Biology"}, "authors": [{"authorId": "34784769", "name": + "L. English"}, {"authorId": "5583964", "name": "I. Macara"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "715270708d9fedd8049b38d956ee4e91790bfd85", + "externalIds": {"MAG": "2497890084", "DOI": "10.1007/978-1-4684-4511-4_2", + "CorpusId": 100424663}, "corpusId": 100424663, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/715270708d9fedd8049b38d956ee4e91790bfd85", + "title": "The Structure and Function of Band 3", "abstract": null, "venue": + "", "year": 1983, "referenceCount": 121, "citationCount": 34, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}], "publicationTypes": + null, "publicationDate": null, "journal": {"volume": "", "pages": "41-87", + "name": ""}, "authors": [{"authorId": "5583964", "name": "I. Macara"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "76ff34d7bd418aa1b010f62e1eff13158d72c818", + "externalIds": {"MAG": "1890087866", "DOI": "10.1016/S0070-2161(08)60582-1", + "CorpusId": 83862727}, "corpusId": 83862727, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/76ff34d7bd418aa1b010f62e1eff13158d72c818", + "title": "Conformational Changes of Na,K-ATPase Necessary for Transport", + "abstract": null, "venue": "", "year": 1983, "referenceCount": 11, "citationCount": + 14, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry"], "s2FieldsOfStudy": [{"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": null, "publicationDate": null, "journal": {"volume": "19", + "pages": "315-322", "name": "Current topics in membranes and transport"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "2060790666", + "name": "C. Carilli"}, {"authorId": "2108905883", "name": "Roderick L. Smith"}, + {"authorId": "49822428", "name": "D. Perlman"}]}, {"paperId": "893b1a85ff6a99305816184cadc1425bde2538a2", + "externalIds": {"MAG": "2068231523", "DOI": "10.1002/JCB.240210102", "CorpusId": + 35710616, "PubMed": "6575972"}, "corpusId": 35710616, "publicationVenue": + {"id": "95e54b20-e12b-4788-9db7-436c24f5bf7d", "name": "Journal of Cellular + Biochemistry", "type": "journal", "alternate_names": ["J Cell Biochem"], "issn": + "0730-2312", "url": "http://www3.interscience.wiley.com/journal/117933916/grouphome/home.html", + "alternate_urls": ["http://www.interscience.wiley.com/jpages/0730-2312/info.html", + "http://www.interscience.wiley.com/jpages/0730-2312/", "https://onlinelibrary.wiley.com/journal/10974644"]}, + "url": "https://www.semanticscholar.org/paper/893b1a85ff6a99305816184cadc1425bde2538a2", + "title": "Ionic regulation of MEL cell commitment", "abstract": "A key event + in the initiation of the dimethyl sulfoxide (DMSO)\u2010induced program of + murine erythroleukemia (MEL) cell differentiation is a rise in the level of + cytoplasmic calcium ions. Our interest in the present study is whether other + inducers of the terminal erythroid differentiation program also act via a + calcium\u2010dependent pathway. Inhibition of calcium transport has been found + to prevent the induction of MEL cell commitment by DMSO, butyric acid (BA), + or hypoxanthine (HX). Enhancement of the calcium flux rate with A23187 or + elevation of cytoplasmic calcium levels with FCCP stimulates the kinetics + of commitment in response to all three inducers. These results suggest that + of the inducers we have tested (DMSO, BA, and HX), all three act to initiate + commitment via a common mechanism which involves modulation of cytoplasmic + calcium levels.", "venue": "Journal of Cellular Biochemistry", "year": 1983, + "referenceCount": 11, "citationCount": 7, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Medicine", "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle", "Study"], "publicationDate": null, + "journal": {"volume": "21", "name": "Journal of Cellular Biochemistry"}, "authors": + [{"authorId": "144579743", "name": "R. Levenson"}, {"authorId": "5583964", + "name": "I. Macara"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": + "10127476", "name": "D. Housman"}]}, {"paperId": "bbb60de51755ffe10991a3d69d227bdfbb20f1a7", + "externalIds": {"MAG": "232897932", "DOI": "10.1016/B978-0-444-80540-9.50013-3", + "CorpusId": 83186045}, "corpusId": 83186045, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/bbb60de51755ffe10991a3d69d227bdfbb20f1a7", + "title": "CHARACTERIZATION OF A PLASMA MEMBRANE KINASE WHICH SPECIFICALLY + PHOSPHORYLATES THE (NA,K)PUMP", "abstract": null, "venue": "", "year": 1983, + "referenceCount": 11, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": + false, "openAccessPdf": null, "fieldsOfStudy": ["Biology"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + {"volume": "", "pages": "73-79", "name": ""}, "authors": [{"authorId": "1723755", + "name": "L. Cantley"}, {"authorId": "34912412", "name": "L. Yeh"}, {"authorId": + "50678030", "name": "L. Ling"}, {"authorId": "152355108", "name": "J. Schulz"}, + {"authorId": "34784769", "name": "L. English"}]}, {"paperId": "fd22aee21ddca538eb038e9e91c0f8481c115d61", + "externalIds": {"MAG": "2005910022", "DOI": "10.1073/PNAS.80.5.1300", "CorpusId": + 20692720, "PubMed": "6131417"}, "corpusId": 20692720, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/fd22aee21ddca538eb038e9e91c0f8481c115d61", + "title": "Clathrin-coated vesicles contain an ATP-dependent proton pump.", + "abstract": "Clathrin-coated vesicles isolated from calf brain contain an + ATP-dependent proton pump. Proton movement was monitored by measuring [14C]methylamine + distribution. Addition of Mg2+ and ATP to coated vesicles equilibrated with + [14C]methylamine resulted in the generation of a 4- to 5-fold concentration + gradient, corresponding to a delta pH of 0.6-0.7 units between the medium + and the acidic inside of the coated vesicles. ATP-dependent [14C]methylamine + uptake was abolished by the proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone + (FCCP) and partially inhibited by the carboxyl reagent N,N''-dicyclohexylcarbodiimide + but was unaffected by the Na+, K+-ATPase inhibitors strophanthidin (100 microM) + and vanadate (10 microM) and the mitochondrial ATPase inhibitors oligomycin + (10 microgram/ml) and aurovertin (1 microgram/ml). GTP, but not the nonhydrolyzable + analog 5''-adenylyl imidodiphosphate, could support [14C]methylamine uptake. + Dissipation of the membrane potential with K+ and valinomycin resulted in + stimulation of [14C]methylamine uptake, whereas both FCCP and valinomycin + stimulated the strophanthidin-resistant ATPase activity. These results are + consistent with the existence of an electrogenic, ATP-dependent proton pump + in clathrin-coated vesicles. This proton pump may play a role in the acidification + events that are essential in receptor-mediated endocytosis.", "venue": "Proceedings + of the National Academy of Sciences of the United States of America", "year": + 1983, "referenceCount": 0, "citationCount": 209, "influentialCitationCount": + 5, "isOpenAccess": true, "openAccessPdf": {"url": "https://www.pnas.org/content/pnas/80/5/1300.full.pdf", + "status": null}, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": + [{"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1983-03-01", "journal": {"volume": + "80 5", "pages": "\n 1300-3\n ", "name": "Proceedings of the + National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "145289081", "name": "M. Forgac"}, {"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "4406446", "name": "B. Wiedenmann"}, {"authorId": + "3500691", "name": "L. Altstiel"}, {"authorId": "6913699", "name": "D. Branton"}]}, + {"paperId": "24c615f319e6c9c131d1f9bb5b749ea8d69adf16", "externalIds": {"MAG": + "2059911212", "DOI": "10.1016/0092-8674(82)90064-2", "CorpusId": 36543606, + "PubMed": "6807553"}, "corpusId": 36543606, "publicationVenue": {"id": "e4782337-db2d-4ab2-8eda-a71d1c60709b", + "name": "Cell", "type": "journal", "alternate_names": ["La Cellule"], "issn": + "0092-8674", "alternate_issns": ["0008-8757"], "url": "https://www.cell.com/", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00928674", + "http://www.cell.com/", "https://www.sciencedirect.com/journal/cell", "https://www.biodiversitylibrary.org/bibliography/7344"]}, + "url": "https://www.semanticscholar.org/paper/24c615f319e6c9c131d1f9bb5b749ea8d69adf16", + "title": "Role of mitochondrial membrane potential in the regulation of murine + erythroleukemia cell differentiation", "abstract": null, "venue": "Cell", + "year": 1982, "referenceCount": 21, "citationCount": 75, "influentialCitationCount": + 2, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Biology"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1982-04-01", "journal": {"volume": "28", "pages": "855-863", "name": "Cell"}, + "authors": [{"authorId": "144579743", "name": "R. Levenson"}, {"authorId": + "5583964", "name": "I. Macara"}, {"authorId": "2108905883", "name": "Roderick + L. Smith"}, {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "10127476", + "name": "D. Housman"}]}, {"paperId": "5384587f623d397dcc3892038184c7c0b8ac4333", + "externalIds": {"MAG": "1645602382", "DOI": "10.1016/s0021-9258(19)68263-3", + "CorpusId": 26044835, "PubMed": "7054181"}, "corpusId": 26044835, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/5384587f623d397dcc3892038184c7c0b8ac4333", + "title": "Evidence that a Na+/Ca2+ antiport system regulates murine erythroleukemia + cell differentiation.", "abstract": null, "venue": "Journal of Biological + Chemistry", "year": 1982, "referenceCount": 0, "citationCount": 147, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Biology", + "Medicine"], "s2FieldsOfStudy": [{"category": "Biology", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1982-01-25", "journal": {"volume": "257 2", "pages": "\n 773-80\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "2169607892", + "name": "R. Smith"}, {"authorId": "5583964", "name": "I. Macara"}, {"authorId": + "144579743", "name": "R. Levenson"}, {"authorId": "10127476", "name": "D. + Housman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "9f1e4e45adc7020f719f0037c74d221296a0485d", + "externalIds": {"MAG": "2002132938", "DOI": "10.1111/J.1749-6632.1982.TB25749.X", + "CorpusId": 32728616, "PubMed": "6301338"}, "corpusId": 32728616, "publicationVenue": + {"id": "fa1f0815-0811-4291-b4fc-8230a6c9bf5b", "name": "Annals of the New + York Academy of Sciences", "type": "journal", "alternate_names": ["Ann n y + Acad Sci"], "issn": "0077-8923", "url": "http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1749-6632", + "alternate_urls": ["http://www.annalsnyas.org/", "http://www.nyas.org/publications/annals/default.aspx", + "https://onlinelibrary.wiley.com/journal/17496632"]}, "url": "https://www.semanticscholar.org/paper/9f1e4e45adc7020f719f0037c74d221296a0485d", + "title": "LOCATION OF BINDING SITES ON THE (Na.K)\u2010ATPase FOR FLUORESCEIN\u20105\u2032\u2010ISOTHIOCYANATE + AND OUABAIN *", "abstract": "Fluorescein-5''-isothiocyanate (FITC) is a specific + inhibitor of the purified mammalian kidney (Na,K)-ATPase.'' This inhibition + is irreversible, is prevented by the presence of 1 mM ATP, and is due to reaction + of one FITC per ATP binding site on the purified Although the FITC-modified + enzyme will not hydrolyze ATP, it is still capable of binding other specific + ligands, including Na+, K'', M&+, phosphate, vanadate, and ouabain, and it + will still hydrolyze pnitrophenyl ph~sphate.''.~.'' For these reasons, and + since iodinated derivatives of FITC have been shown to specifically react + at the adenine ring binding site of lactate dehydrogenase'' and yeast hexokinase,'' + it seems likely that FITC also reacts at the adenine ring binding site of + (Na,K)-ATPase. It was of interest to determine the Iocation of the FITC site + in the primary sequence a n d in the native folded structure. Using specific + trypsin and chymotrypsin cleavage of the FITC-modified enzyme, we were able + to show that FITC reacts at a residue on the carboxy half of the a-subunit. + This result was surprising since the active site aspartate residue that is + phosphorylated is on the amino terminal half of the protein. In addition, + we found that in the presence of ouabain, a fraction of the protein containing + the FITC-modified residue can be completely excised from the protein and solubilized + away from the mernbranee3 This fragment was localized near the middle of the + 77,000-dalton carboxy terminal chymotryptic fragment of the a-chain (see FIGURE + 11. Since ouabain binding to the enzyme affects the environment of the FITC + modification site, it was of interest to determine the distance between these + sites in the native structure. Using 3H-anthroyl-ouabain as an energy-transfer + donor and FITC as the acceptor, we determined by fluorescence resonance energy + transfer that these two binding domains are separated by 66-83 A.3 This distance + is considerably greater than the width of a bilayer. Thus, an extensive conformational + change must occur during the transport cycle since these two sites alter their + affinities for their respective ligands as the enzyme switches from the El + to the E, conformational states. The drawing in FIGURE 1 is a hypothetical + proposal for the folding of the a-subunit in the membrane based on results + discussed here and previously published results from a number of other laboratories. + The critical points are: [I) The aspartate group that accepts the terminal + phosphate of ATP and the amino acids that make up the adenine ring binding + domain (i.e., the FITC-reactive site) are at least 150 residues apart in the + sequence. (2) These groups are separated by a trypsin-sensitive site, which + is blocked by ATP or Na+ but exposed in the", "venue": "Annals of the New + York Academy of Sciences", "year": 1982, "referenceCount": 10, "citationCount": + 11, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1982-12-01", "journal": {"volume": "402", "name": "Annals of the New York + Academy of Sciences"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "2060790666", "name": "C. Carilli"}, {"authorId": "2284479", + "name": "R. Farley"}, {"authorId": "49822428", "name": "D. Perlman"}]}, {"paperId": + "c7a27fc21d8639e0feb4ce48e7e44ad21bcf6261", "externalIds": {"MAG": "1564076413", + "CorpusId": 33714376, "PubMed": "6279607"}, "corpusId": 33714376, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/c7a27fc21d8639e0feb4ce48e7e44ad21bcf6261", + "title": "The active site structure of Na+- and K+-stimulated ATPase. Location + of a specific fluorescein isothiocyanate reactive site.", "abstract": "Fluorescein + 5''-isothiocyanate (FITC) has been shown to specifically inactivate the Na+- + and K+-stimulated adenosine triphosphatase ((Na,K)-ATPase) at low concentrations + (Karlish, S. J. D. (1979) Na+,K+ATPase Structure and Kinetics 115-128). The + site of modification of purified dog kidney (Na,K)-ATPase by FITC has been + investigated by enzymatic cleavage and fluorescence resonance energy transfer. + The binding of FITC, which occurs at a stoichiometry of approximately one + site per ATP binding site, causes an ATP-protectable inactivation of ATPase + activity suggesting that it is reacting at the ATP hydrolysis site. The FITC + reaction site apparently is located near the center of the COOH-terminal 77,000-dalton + peptide fragment obtained by chymotryptic cleavage of the alpha subunit. Addition + of ouabain to the native enzyme in the presence of chymotrypsin enhances cleavage + at this site and releases the fluorescein moiety from the membrane. It is + further shown that the distance from the FITC reaction site to the ouabain + binding site, as judged by fluorescence resonance energy transfer from anthroyl + ouabain to FITC, is approximately 74 A. These results demonstrate that ouabain + inhibits the (Na,K)-ATPase by causing a protein conformational change which + extends an unusually large distance across the membrane.", "venue": "Journal + of Biological Chemistry", "year": 1982, "referenceCount": 1, "citationCount": + 93, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1982-05-25", "journal": {"volume": "257 10", "pages": "\n 5601-6\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "2060790666", + "name": "C. Carilli"}, {"authorId": "2284479", "name": "R. Farley"}, {"authorId": + "49822428", "name": "D. Perlman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "7b0a02bd653b60e7b2960a568a2041011551a5d2", "externalIds": {"MAG": + "36684287", "DOI": "10.1016/B978-0-12-152511-8.50012-8", "CorpusId": 81930800}, + "corpusId": 81930800, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/7b0a02bd653b60e7b2960a568a2041011551a5d2", + "title": "Structure and Mechanism of the (Na,K)-ATPase", "abstract": null, + "venue": "", "year": 1981, "referenceCount": 148, "citationCount": 270, "influentialCitationCount": + 3, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Biology", "source": "s2-fos-model"}], "publicationTypes": ["Review"], "publicationDate": + null, "journal": {"volume": "11", "pages": "201-237", "name": ""}, "authors": + [{"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "9162b6ab998e995be916bb28ac8e70a67bb379bf", + "externalIds": {"MAG": "2021341443", "DOI": "10.1021/BI00523A009", "CorpusId": + 19370125, "PubMed": "7295699"}, "corpusId": 19370125, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/9162b6ab998e995be916bb28ac8e70a67bb379bf", + "title": "Mechanism of anion exchange across the red cell membrane by band + 3: interactions between stilbenedisulfonate and NAP-taurine binding sites.", + "abstract": "Anion exchange across the erythrocyte membrane can be inhibited + competitively by stilbenedisulfonates, which bind to the external transport + of the band 3 protein, and noncompetitively by external NAP-taurine [2-[N-(4-azido-2-nitrophenyl)amino]ethanesulfonate], + which it has been suggested binds to a \"modifier site\" [Knauf, P. A., Ship. + S., Breur, W., MCCulloch, L., & Rothstein, A. (1978) J. Gen. Physiol. 72, + 604-630]. The binding of the two types of inhibitor of erythrocyte membranes + is shown in the present study to be competitive, indicating that binding to + the same subunit of band 3 is mutually exclusive. Covalent labeling of red + cells with a stilbenedisulfonate [4-benzamido-4''-isothiocyano-stilbene-2,2''-disulfonate + (BIDS)] to 80% saturation had no detectable effect upon the Ki for inhibition + of [32P]phosphate influx by NAP-taurine, indicating that when bound to adjacent + subunits in the band 3 dimer, the two types of inhibitor do not interact. + In addition to the external NAP-taurine site, a second high-affinity NAP-taurine + site (Kd = 15 microM) was detected on the cytoplasmic side of red cell membranes. + This site is less than 51 A from the disulfonic stilbene binding site, as + judged by fluorescence resonance energy transfer from BIDS to NAP-taurine. + Binding at this site is not affected by covalent attachment of BIDS, and no + clear role for this site in transport could be determined. On the basis of + these studies we present a model indicating that disulfonic stilbenes bind + to a site which overlaps both the anion transport site and the modifier site + on a band 3 monomer and suggests that the modifier site may be part of a transporting + gate.", "venue": "Biochemistry", "year": 1981, "referenceCount": 16, "citationCount": + 45, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1981-09-29", "journal": {"volume": "20 20", "pages": "\n 5695-701\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "5583964", "name": "I. Macara"}, + {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": "d4487da1249d636d01e2b45ddebe82561f69665a", + "externalIds": {"MAG": "1968550320", "PubMedCentral": "2111862", "DOI": "10.1083/JCB.90.2.542", + "CorpusId": 18168731, "PubMed": "6793600"}, "corpusId": 18168731, "publicationVenue": + {"id": "bf59074e-18fd-4f9a-a1b0-a9bafc16f518", "name": "Journal of Cell Biology", + "type": "journal", "alternate_names": ["J Cell Biology"], "issn": "0021-9525", + "url": "http://www.pubmedcentral.nih.gov/tocrender.fcgi?action=archive&journal=482", + "alternate_urls": ["http://www.jstor.org/journals/00219525.html", "https://www.jstor.org/journal/jcellbiology", + "http://www.jcb.org/"]}, "url": "https://www.semanticscholar.org/paper/d4487da1249d636d01e2b45ddebe82561f69665a", + "title": "Calcium regulates the commitment of murine erythroleukemia cells + to terminal erythroid differentiation", "abstract": "An alteration in the + rate of calcium transport appears to be the rate- limiting event for the commitment + of murine erythroleukemia (MEL) cells to initiate a program of terminal erythroid + differentiation. The dimethyl sulfoxide (DMSO)-induced commitment of MEL cells + to erythroid differentiation can be inhibited by treatment of cells with the + calcium- chelating agent EGTA. Upon removal of EGTA, cells initiate commitment + without the 12-h lag normally observed after treatment with DMSO alone. Treatment + of cells with DMSO in the presence of calcium ionophore A23187 causes cells + to initiate commitment from time zero with no lag. These results suggest that + the lag is the time required for DMSO to alter the calcium transport properties + of the cell.", "venue": "Journal of Cell Biology", "year": 1981, "referenceCount": + 17, "citationCount": 74, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://rupress.org/jcb/article-pdf/90/2/542/1266884/542.pdf", + "status": null}, "fieldsOfStudy": ["Biology", "Medicine"], "s2FieldsOfStudy": + [{"category": "Biology", "source": "external"}, {"category": "Medicine", "source": + "external"}, {"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1981-08-01", "journal": {"volume": + "90", "pages": "542 - 544", "name": "The Journal of Cell Biology"}, "authors": + [{"authorId": "145912522", "name": "K. Bridges"}, {"authorId": "144579743", + "name": "R. Levenson"}, {"authorId": "10127476", "name": "D. Housman"}, {"authorId": + "1723755", "name": "L. Cantley"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '219401' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:57 GMT + Via: + - 1.1 5e55a7a4861ab03c7d80b37b8cc55e74.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - v_u7Y9XFzrAPQLwrcXykDAQB_boTMyTmUrEFpwiskIuFP6oKgK0lKA== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOcrF-pvHcFcjA= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '219401' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:57 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - a4602c41-58b8-4c32-8970-e49748655321 + status: + code: 200 + message: OK +- request: + body: null + headers: + Accept: + - '*/*' + Accept-Encoding: + - gzip, deflate + Connection: + - keep-alive + User-Agent: + - python-requests/2.28.1 + method: GET + uri: https://api.semanticscholar.org/graph/v1/author/1723755/papers?&fields=abstract,authors,citationCount,corpusId,externalIds,fieldsOfStudy,influentialCitationCount,isOpenAccess,journal,openAccessPdf,paperId,publicationDate,publicationTypes,publicationVenue,referenceCount,s2FieldsOfStudy,title,url,venue,year&offset=900&limit=100 + response: + body: + string: '{"offset": 900, "data": [{"paperId": "ed56f186df239bbff63f62a57e00123c91ad1610", + "externalIds": {"MAG": "2048328629", "DOI": "10.1021/BI00521A001", "CorpusId": + 1688960, "PubMed": "7295667"}, "corpusId": 1688960, "publicationVenue": {"id": + "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": "journal", + "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/ed56f186df239bbff63f62a57e00123c91ad1610", + "title": "Interactions between transport inhibitors at the anion binding sites + of the band 3 dimer.", "abstract": "Evidence is presented that the binding + of aromatic disulfonates to the external transport sites of the red cell anion-exchange + protein (band 3) can exhibit negative cooperativity. Fluorescence resonance + energy transfer has been used to compare the affinities of an aromatic disulfonate + 4,4''-bis-(4-nitro-2,1,3-benzoxadiazolyl)dihydrostilbene-2,2''-disulfonate[H2(NBD)2DS] + for \"empty\" band 3 dimers (in which neither external transport site is occupied) + and for \"half-filled\" dimers (in which one site per dimer is occupied by + a covalently attached fluorescent stilbenedisulfonate). H2(NBD)2DS apparently + binds to the external anion transport site since it is a potent inhibitor + of [35S]sulfate influx into red cells (Ki = 20-50 nM), binds reversibly to + approximately one site per band 3 monomer (1.6 X 10(6) sites/cell), and is + displaced by covalent labeling with a disulfonic stilbene. The affinity of + H2(NBD)2DS for membranes in which 80% of the transport sites are occupied + by covalently attached 4-benzamido-4''-isothiocyanostilbene-2,2''-disulfonate + (BIDS) was approximately 1 order of magnitude lower than that for unmodified + membranes. However, when a similar proportion of the transport sites on red + cells was blocked by reaction with BIDS, [35S]sulfate was taken up with a + lower Vmax but with a Km identical with that observed for unmodified cells, + suggesting that no subunit interactions are necessary for transport. Therefore, + in order to test whether the observed negative cooperativity of aromatic disulfonate + binding could be ascribed simply to steric hindrance, the distance between + transport sites was measured by fluorescence resonance energy transfer. H2(NBD)2DS + and eosin maleimide were used as acceptors, with BIDS as donor. Transfer efficiencies + were determined by donor fluorescence quenching, by acceptor fluorescence + enhancement, and from donor lifetime changes. Uncertainties in the distance + were estimated from measured depolarization factors. The donor-acceptor distance + was found to be only 28-52 A. Since the probes are large molecules, they could + therefore be very close together, and the observed negative cooperativity + might be explained by overlapping sites. The results suggest that the subunits + of a band 3 dimer transport anions independently but that access to the transport + sites may be provided by a cavity between the subunits.", "venue": "Biochemistry", + "year": 1981, "referenceCount": 20, "citationCount": 53, "influentialCitationCount": + 1, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1981-09-01", "journal": + {"volume": "20 18", "pages": "\n 5095-105\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "5583964", "name": "I. Macara"}, {"authorId": "1723755", + "name": "L. Cantley"}]}, {"paperId": "71cb4e8042446a747af14345c888677b882166b3", + "externalIds": {"MAG": "2070295305", "DOI": "10.1073/PNAS.77.10.5948", "CorpusId": + 25967675, "PubMed": "6934526"}, "corpusId": 25967675, "publicationVenue": + {"id": "bb95bf2e-8383-4748-bf9d-d6906d091085", "name": "Proceedings of the + National Academy of Sciences of the United States of America", "type": "journal", + "alternate_names": ["Proc National Acad Sci u s Am"], "issn": "0027-8424", + "url": "https://www.jstor.org/journal/procnatiacadscie", "alternate_urls": + ["https://www.pnas.org/", "http://www.jstor.org/journals/00278424.html", "http://www.pnas.org/"]}, + "url": "https://www.semanticscholar.org/paper/71cb4e8042446a747af14345c888677b882166b3", + "title": "Amiloride inhibits murine erythroleukemia cell differentiation: + evidence for a Ca2+ requirement for commitment.", "abstract": "The effect + of amiloride (an inhibitor of passive Na+ transport in many tissues) on the + differentiation of murine erythroleukemia cells was investigated. Amiloride + completely blocked the dimethyl sulfoxide (Me2SO)-induced erythroid differentiation + of cells at a concentration (10 microgram/ml) that did not affect cell proliferation. + Amiloride also prevented the decrease in cell volume normally observed afte + a 20-hr exposure to Me2SO. The ratio of total cell Na+ to total cell water + was essentially the same for control cells, Me2SO-treated cells, and cells + treated with Me2SO plus amiloride. However, cells treated for 24 hr with Me2SO + had a rate of Ca2+ uptake that was twice that of untreated cells and a similarly + higher Ca2+ content. Addition of amiloride plus Me2SO prevented both the increase + in Ca2+ uptake rate and the increase in Ca2+ content. Cells grown in the presence + of Me2SO plus amiloride initiated differentiation immediately after removal + of amiloride or addition of the Ca2+ ionophore A23187 (1 microgram/ml). Addition + of sufficient ethylene glycol bis(beta-aminoethyl ether)-N,N,N'',N''-tetraacetic + acid to reduce free extracellular Ca2+ to submicromolar levels prevented Me2SO-induced + differentiation while only slightly affecting cell proliferation. These results + suggest that an increase in in the Ca2+ level is an essential step in Me2SO + induction, that amiloride either directly or indirectly inhibits this process, + and that Me2SO has an early effect on cells that is necessary for differentiation + and is not mimicked by A23187.", "venue": "Proceedings of the National Academy + of Sciences of the United States of America", "year": 1980, "referenceCount": + 0, "citationCount": 96, "influentialCitationCount": 0, "isOpenAccess": true, + "openAccessPdf": {"url": "https://europepmc.org/articles/pmc350189?pdf=render", + "status": null}, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1980-10-01", "journal": + {"volume": "77 10", "pages": "\n 5948-52\n ", "name": "Proceedings + of the National Academy of Sciences of the United States of America"}, "authors": + [{"authorId": "144579743", "name": "R. Levenson"}, {"authorId": "10127476", + "name": "D. Housman"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "7c09c8649f040bbc281ecdce37ac8d9b9f3f09d2", "externalIds": {"MAG": "2092308816", + "DOI": "10.1016/0304-4165(80)90268-8", "CorpusId": 28159214, "PubMed": "6245716"}, + "corpusId": 28159214, "publicationVenue": {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", + "name": "Biochimica et Biophysica Acta", "type": "journal", "alternate_names": + ["Biochim Biophys Acta"], "issn": "0006-3002", "alternate_issns": ["1878-2434"], + "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/7c09c8649f040bbc281ecdce37ac8d9b9f3f09d2", + "title": "Glutathione reduces cytoplasmic vanadate. Mechanism and physiological + implications.", "abstract": null, "venue": "Biochimica et Biophysica Acta", + "year": 1980, "referenceCount": 29, "citationCount": 233, "influentialCitationCount": + 5, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1980-04-17", "journal": {"volume": + "629 1", "pages": "\n 95-106\n ", "name": "Biochimica et biophysica + acta"}, "authors": [{"authorId": "5583964", "name": "I. Macara"}, {"authorId": + "6237815", "name": "K. Kustin"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "7febd16c83d434aeed405d5bc8be94af173610a4", "externalIds": {"MAG": + "1480907586", "DOI": "10.1016/s0021-9258(18)43471-0", "CorpusId": 21175170, + "PubMed": "6253455"}, "corpusId": 21175170, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/7febd16c83d434aeed405d5bc8be94af173610a4", + "title": "A study of the vanadate-trapped state of the (Na,K)-ATPase. Evidence + against interacting nucleotide site models.", "abstract": null, "venue": "Journal + of Biological Chemistry", "year": 1980, "referenceCount": 1, "citationCount": + 90, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Medicine", "Chemistry"], "s2FieldsOfStudy": [{"category": + "Medicine", "source": "external"}, {"category": "Chemistry", "source": "external"}, + {"category": "Biology", "source": "s2-fos-model"}, {"category": "Chemistry", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1980-10-25", "journal": {"volume": "255 20", "pages": "\n 9852-9\n ", + "name": "The Journal of biological chemistry"}, "authors": [{"authorId": "2169607892", + "name": "R. Smith"}, {"authorId": "2073410407", "name": "K. Zinn"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "806692eef99ab815254437bdb974f233d2137c88", + "externalIds": {"MAG": "2024850488", "DOI": "10.1016/0005-2736(80)90189-3", + "CorpusId": 22762013, "PubMed": "6250591"}, "corpusId": 22762013, "publicationVenue": + {"id": "08ee3346-e195-4333-b008-be3a4f9e23cd", "name": "Biochimica et Biophysica + Acta", "type": "journal", "alternate_names": ["Biochim Biophys Acta"], "issn": + "0006-3002", "alternate_issns": ["1878-2434"], "url": "https://www.elsevier.com/life-sciences/biochemistry-genetics-and-molecular-biology/journals/bba", + "alternate_urls": ["http://www.sciencedirect.com/science/journal/00063002", + "http://www.elsevier.com/wps/find/journaldescription.cws_home/506062/description#description"]}, + "url": "https://www.semanticscholar.org/paper/806692eef99ab815254437bdb974f233d2137c88", + "title": "Structural changes in (Na+ + K+)-ATPase accompanying detergent inactivation.", + "abstract": null, "venue": "Biochimica et Biophysica Acta", "year": 1980, + "referenceCount": 29, "citationCount": 10, "influentialCitationCount": 0, + "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1980-07-04", "journal": {"volume": + "599 2", "pages": "\n 436-47\n ", "name": "Biochimica et biophysica + acta"}, "authors": [{"authorId": "2061032597", "name": "L. Powell"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "46a04a9aa293d297cdf93b7c3a96797b30e27525", + "externalIds": {"MAG": "2094264339", "DOI": "10.1021/BI00588A008", "CorpusId": + 38082120, "PubMed": "497152"}, "corpusId": 38082120, "publicationVenue": {"id": + "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": "journal", + "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/46a04a9aa293d297cdf93b7c3a96797b30e27525", + "title": "Location of the stilbenedisulfonate binding site of the human erythrocyte + anion-exchange system by resonance energy transfer.", "abstract": "The stilbenedisulfonate + inhibitory site of the human erythrocyte anion-exchange system has been characterized + by using serveral fluorescent stilbenedisulfonates. The covalent inhibitor + 4-benzamido-4''-isothiocyanostilbene-2,2''-disulfonate (BIDS) reacts specifically + with the band 3 protein of the plasma membrane when added to intact erythrocytes, + and the reversible inhibitors 4,4''-dibenzamidostilbene-2,2''-disulfonate + (DBDS) and 4-benzamido-4''-aminostilbene-2,2''-disulfonate (BADS) show a fluorescence + enhancement upon binding to the inhibitory site on erythrocyte ghosts. The + fluorescence properties of all three bound probes indicate a rigid, hydrophobic + site with nearby tryptophan residues. The Triton X-100 solublized and purified + band 3 protein has similar affinities for DBDS, BADS, and 4,4''-dinitrostilbene-2,2''-disulfonate + (DNDS) to those observed on intact erythrocytes and erythrocyte ghosts, showing + that the anion binding site is not perturbed by the solubilization procedure. + The distance between the stilbenedisulfonate binding site and a group of cysteine + residues on the 40 000-dalton amino-terminal cytoplasmic domain of band 3 + was measured by the fluorescence resonance energy transfer technique. Four + different fluorescent sulfhydryl reagents were used as either energy transfer + donors or energy transfer acceptors in combination with the stilbenedisulfonates + (BIDS, DBDS, BADS, and DNDS). Efficiencies of transfer were measured by sensitized + emisssion, donor quenching, and donor lifetime changes. Although these sites + are approachable from opposite sides of the membrane by impermeant reagents, + they are separated by only 34--42 A, indicating that the anion binding site + is located in a protein cleft which extends some distance into the membrane.", + "venue": "Biochemistry", "year": 1979, "referenceCount": 0, "citationCount": + 93, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": [{"category": + "Chemistry", "source": "external"}, {"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "s2-fos-model"}, {"category": "Biology", + "source": "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1979-10-16", "journal": {"volume": "18 21", "pages": "\n 4505-16\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "2113654796", "name": "A. + Rao"}, {"authorId": "2107715199", "name": "P. Martin"}, {"authorId": "3310395", + "name": "R. Reithmeier"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "8d1a31924429e4045ce8ef4417db41788aa52c55", "externalIds": {"MAG": + "1980265359", "DOI": "10.1038/282520A0", "CorpusId": 4306035, "PubMed": "503233"}, + "corpusId": 4306035, "publicationVenue": {"id": "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", + "name": "Nature", "type": "journal", "issn": "0028-0836", "url": "https://www.nature.com/", + "alternate_urls": ["http://www.nature.com/nature/", "https://www.nature.com/nature/", + "http://www.nature.com/nature/archive/index.html"]}, "url": "https://www.semanticscholar.org/paper/8d1a31924429e4045ce8ef4417db41788aa52c55", + "title": "Human erythrocyte anion exchange site characterised using a fluorescent + probe", "abstract": null, "venue": "Nature", "year": 1979, "referenceCount": + 4, "citationCount": 34, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}, + {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1979-11-29", "journal": {"volume": + "282", "pages": "520-522", "name": "Nature"}, "authors": [{"authorId": "6156118", + "name": "J. Dix"}, {"authorId": "4265624", "name": "A. Verkman"}, {"authorId": + "4595664", "name": "A. K. Solomon"}, {"authorId": "1723755", "name": "L. Cantley"}]}, + {"paperId": "9d3256dd8e7e75a9d8de4457630ae7ee8dddce49", "externalIds": {"MAG": + "1528985492", "DOI": "10.1016/s0021-9258(17)37721-9", "CorpusId": 32153077, + "PubMed": "217870"}, "corpusId": 32153077, "publicationVenue": {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", + "name": "Journal of Biological Chemistry", "type": "journal", "alternate_names": + ["J Biological Chem"], "issn": "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/9d3256dd8e7e75a9d8de4457630ae7ee8dddce49", + "title": "The fate of cytoplasmic vanadium. Implications on (NA,K)-ATPase + inhibition.", "abstract": null, "venue": "Journal of Biological Chemistry", + "year": 1979, "referenceCount": 0, "citationCount": 246, "influentialCitationCount": + 2, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1979-03-25", "journal": {"volume": + "254 6", "pages": "\n 1781-4\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "145150128", "name": "P. Aisen"}]}, {"paperId": "334f40046bdc39bcffc3a345de1fb83e2e145cd9", + "externalIds": {"MAG": "2033463478", "DOI": "10.1038/272552A0", "CorpusId": + 4253398, "PubMed": "211419"}, "corpusId": 4253398, "publicationVenue": {"id": + "6c24a0a0-b07d-4d7b-a19b-fd09a3ed453a", "name": "Nature", "type": "journal", + "issn": "0028-0836", "url": "https://www.nature.com/", "alternate_urls": ["http://www.nature.com/nature/", + "https://www.nature.com/nature/", "http://www.nature.com/nature/archive/index.html"]}, + "url": "https://www.semanticscholar.org/paper/334f40046bdc39bcffc3a345de1fb83e2e145cd9", + "title": "Vanadate inhibits the red cell (Na+, K+) ATPase from the cytoplasmic + side", "abstract": null, "venue": "Nature", "year": 1978, "referenceCount": + 14, "citationCount": 350, "influentialCitationCount": 8, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1978-04-06", "journal": + {"volume": "272", "pages": "552-554", "name": "Nature"}, "authors": [{"authorId": + "1723755", "name": "L. Cantley"}, {"authorId": "3397888", "name": "M. Resh"}, + {"authorId": "2219731", "name": "G. Guidotti"}]}, {"paperId": "6ab4b81575435abd775ca99bdf20923451991723", + "externalIds": {"MAG": "2051820316", "DOI": "10.1021/JA00484A053", "CorpusId": + 85222955}, "corpusId": 85222955, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/6ab4b81575435abd775ca99bdf20923451991723", + "title": "Norepinephrine complexes and reduced vanadium(V) to reverse vanadate + inhibition of the (sodium, potassium ion)-dependent ATPase", "abstract": null, + "venue": "", "year": 1978, "referenceCount": 0, "citationCount": 80, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry"], + "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, {"category": + "Chemistry", "source": "s2-fos-model"}], "publicationTypes": null, "publicationDate": + "1978-08-01", "journal": {"volume": "100", "pages": "5210-5212", "name": "Journal + of the American Chemical Society"}, "authors": [{"authorId": "1723755", "name": + "L. Cantley"}, {"authorId": "143945662", "name": "J. Ferguson"}, {"authorId": + "6237815", "name": "K. Kustin"}]}, {"paperId": "b4aa3804656faa15b4e890c790c3bb280b369665", + "externalIds": {"MAG": "2025657863", "DOI": "10.1021/BI00596A006", "CorpusId": + 20399818, "PubMed": "145873"}, "corpusId": 20399818, "publicationVenue": {"id": + "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": "journal", + "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/b4aa3804656faa15b4e890c790c3bb280b369665", + "title": "Reaction of (Na-K)ATPase with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole: + evidence for an essential tyrosine at the active site.", "abstract": "The + reaction of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole [NBD-Cl] with purified + eel electrophax Na+ and K+ stimulated adenosine triphosphatase [(Na-K)ATPase] + has been monitored by changes in the (Na-K)ATPase activity, the K+ stimulated + p-nitrophenyl phosphatase [PNPase] activity, and the protein ultraviolet absorption + spectrum. The NBD-Cl reacts with two tyrosine residues per mol of enzyme (approximately + 6-7 nmol/mg of protein), as judged by changes in protein absorption spectra + and incorporation of [14C]NBD-Cl. The modified tyrosine groups are located + on the Mr = 95 000 polypeptide chain and react at different rates. Only one + tyrosine modification is necessary for complete inhibition of (Na-K)ATPase + activity, although both must be modified for complete inhibition of PNPase + activity. Reversal of these modifications by 2-mercaptoethanol restores 65% + of both activities. Na+ increases the rate of tyrosine modification, K+ decreases + the rate, and ATP affords the more reactive tyrosine group complete protection. + NBD-Cl modification of approximately 6-7 nmol of tyrosine groups/mg of protein + results in a large decrease in ATP affinity as judged by equilibrium binding. + These results are compared with similar results obtained from NBD-Cl modification + of the coupling factors of oxidative phosphorylation and photophosphorylation. + A model is presented suggesting an asymmetric arrangement of two 95 000 polypeptide + chains with a single tyrosine residue at the ATP site.", "venue": "Biochemistry", + "year": 1978, "referenceCount": 46, "citationCount": 64, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1978-02-07", "journal": {"volume": + "17 3", "pages": "\n 418-25\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "4616517", + "name": "J. Gelles"}, {"authorId": "5095505", "name": "L. Josephson"}]}, {"paperId": + "fc2e434d53c2fcf193dd89519c278e5a676bcfc0", "externalIds": {"MAG": "1824817217", + "CorpusId": 41917525, "PubMed": "212422"}, "corpusId": 41917525, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/fc2e434d53c2fcf193dd89519c278e5a676bcfc0", + "title": "A characterization of vanadate interactions with the (Na,K)-ATPase. + Mechanistic and regulatory implications.", "abstract": "The interaction of + vanadium in the +5 oxidation state (vanadate) with purified dog kidney Na+ + and K+-stim- ulated adenosine trlphosphatase [(Na,K)-ATPase] has been studied + using equilibrium binding, steady state kinetics, and measurements of relaxation + kinetics. Van- adate binds to one high affinity site (Kl = 4 no) and one low + afinity site (Kz = 0.5", "venue": "Journal of Biological Chemistry", "year": + 1978, "referenceCount": 3, "citationCount": 451, "influentialCitationCount": + 6, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1978-10-25", "journal": {"volume": + "253 20", "pages": "\n 7361-8\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5601835", "name": "L. Cantley"}, {"authorId": "5095505", "name": + "L. Josephson"}]}, {"paperId": "94a9c6dd32da30388c035b8ffa3e362adcf81a13", + "externalIds": {"MAG": "2071273962", "DOI": "10.1021/BI00640A006", "CorpusId": + 12403766, "PubMed": "143955"}, "corpusId": 12403766, "publicationVenue": {"id": + "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": "journal", + "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/94a9c6dd32da30388c035b8ffa3e362adcf81a13", + "title": "Isolation of a potent (Na-K)ATPase inhibitor from striated muscle.", + "abstract": null, "venue": "Biochemistry", "year": 1977, "referenceCount": + 16, "citationCount": 224, "influentialCitationCount": 3, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", "Medicine"], "s2FieldsOfStudy": + [{"category": "Chemistry", "source": "external"}, {"category": "Medicine", + "source": "external"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1977-10-18", "journal": + {"volume": "16 21", "pages": "\n 4572-8\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "5095505", "name": "L. Josephson"}, {"authorId": + "1723755", "name": "L. Cantley"}]}, {"paperId": "c07c1345f4b920f35507ddeb521e30a9f119e58f", + "externalIds": {"MAG": "1520021552", "DOI": "10.1016/s0021-9258(17)40978-1", + "CorpusId": 44622950, "PubMed": "144127"}, "corpusId": 44622950, "publicationVenue": + {"id": "099a2ecc-54f9-42d3-9ea0-0189027aa04f", "name": "Journal of Biological + Chemistry", "type": "journal", "alternate_names": ["J Biological Chem"], "issn": + "0021-9258", "url": "http://ejournals.ebsco.com/direct.asp?JournalID=101729", + "alternate_urls": ["https://www.jbc.org/", "http://www.jbc.org/"]}, "url": + "https://www.semanticscholar.org/paper/c07c1345f4b920f35507ddeb521e30a9f119e58f", + "title": "Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived + from muscle.", "abstract": null, "venue": "Journal of Biological Chemistry", + "year": 1977, "referenceCount": 0, "citationCount": 764, "influentialCitationCount": + 18, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + ["JournalArticle"], "publicationDate": "1977-11-10", "journal": {"volume": + "252 21", "pages": "\n 7421-3\n ", "name": "The Journal of + biological chemistry"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5095505", "name": "L. Josephson"}, {"authorId": "50212668", + "name": "R. Warner"}, {"authorId": "2285635", "name": "M. Yanagisawa"}, {"authorId": + "4383026", "name": "C. Lechene"}, {"authorId": "2219731", "name": "G. Guidotti"}]}, + {"paperId": "1933b03efcc743de8ffcfac014a539327914a3f8", "externalIds": {"MAG": + "2035636114", "DOI": "10.1021/BI00646A001", "CorpusId": 32111571, "PubMed": + "1247500"}, "corpusId": 32111571, "publicationVenue": {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", + "name": "Biochemistry", "type": "journal", "issn": "0006-2960", "alternate_issns": + ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", "alternate_urls": + ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/1933b03efcc743de8ffcfac014a539327914a3f8", + "title": "Investigation of quercetin binding sites on chloroplast coupling + factor 1.", "abstract": "The quercetin binding sites on spinach chloroplast + coupling factor 1 (CF1) have been investigated using direct and competitive + binding, stopped-flow, temperature-jump, and fluorescence resonance energy + transfer measurements. It was found that 8-anilino-1-naphthalensulfonic acid + (ANS) competes with quercetin binding at two sites on the solubilized enzyme + which are distinct from the two tight nucleotide binding sites and the 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole + (NBD-Cl) reactive site. The bimolecular association of quercetin with CF1 + is too fast to measure directly and is followed by two slower conformational + changes. The distances from the tight nucleotide sites to the quercetin-ANS + sites were estimated as 40-48 A by fluorescence resonance energy transfer + using 1,N6-ethenoadenosine diphosphate and 1,N6-ethenoadenylyl imidodiphosphate + as donors and quercetin as the acceptor. The distance from the quercetin-ANS + site to the NBD-C1 reactive site was found to be about 30 A using ANS as a + donor and NBD-C1 reacted with a tyrosine group on CF1 as the energy acceptor. + A model is proposed for the relative location of these sites on CF1.", "venue": + "Biochemistry", "year": 1976, "referenceCount": 21, "citationCount": 57, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1976-01-13", "journal": + {"volume": "15 1", "pages": "\n 1-8\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5738308", + "name": "G. Hammes"}]}, {"paperId": "8658daf8f8dab887596f8a62f5a2be942e6d7d28", + "externalIds": {"MAG": "2035688421", "DOI": "10.1021/BI00646A002", "CorpusId": + 1211586, "PubMed": "129152"}, "corpusId": 1211586, "publicationVenue": {"id": + "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": "journal", + "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/8658daf8f8dab887596f8a62f5a2be942e6d7d28", + "title": "Characterization of sulfhydryl groups on chloroplast coupling factor + 1 exposed by heat activation.", "abstract": "Two sulfhydryl groups in the + gamma subunit of solubilized chloroplast coupling factor 1 (CF1) are exposed + by heat activating the enzyme. These two groups have been selectively labeled + with [3H]-N-ethylmaleimide, N-[p-(2-benzoxazolyl)phenyl]maleimide (NBPM), + and N-(4-dimethylamino-3,5-dinitrophenyl)maleimide (DDPM). Modifying these + groups did not appreciably effect Ca2+-ATPase activity, the ability of the + enzyme to bind quercetin and 1,N6-ethenoadenosine diphosphate (epsilonADP), + or the ability of the enzyme to react with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole + (NBD-C1). Fluorescence resonance energy transfer was used to measure the distance + from the sulfhydryl groups on the gamma subunit to the quercetin sites, the + NBD-C1 reactive sites, and the tight nucleotide sites on CF1 using the donor-acceptor + pairs NBPM-quercetin, NBPM-NBD, and epsilonADP-DDPM, respectively. The distance + from the sulfhydryl groups to the quercetin sites was found to be less than + 30 A, the distance to the NBD-C1 reactive was 34-41 A, and the distance to + the tight nucleotide sites as greater than 40 A. A three-dimensional symmetrical + model is proposed for the relative positions of sites on CF1.", "venue": "Biochemistry", + "year": 1976, "referenceCount": 27, "citationCount": 30, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1976-01-13", "journal": + {"volume": "15 1", "pages": "\n 9-14\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5738308", + "name": "G. Hammes"}]}, {"paperId": "988933ac97cd043955512a566ce3b19a0c8aa3e9", + "externalIds": {"MAG": "1967263378", "DOI": "10.1021/BI00669A013", "CorpusId": + 33424448, "PubMed": "136980"}, "corpusId": 33424448, "publicationVenue": {"id": + "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": "journal", + "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/988933ac97cd043955512a566ce3b19a0c8aa3e9", + "title": "A slow interconversion between active and inactive states of the + (Na-K)ATPase.", "abstract": "We have examined slow changes in the rate of + ATP hydrolysis for purified dog kidney Na+ and K+ stimulated adenosine triphosphatase + [(Na-K)ATPase] at various concentrations of free Mg2+, Mg-ATP, K+, and Na+. + The effect of these ligands on the rate of ATP hydrolysis is explained by + a rapid binding step determining the initial rate of turnover followed by + a slow conformational change. Inactivation of enzyme stored in the presence + of ethylenediaminetetraacetic acid occurs upon adding free Mg2+, Mg-ATP, and + K+; reactivation may be achieved if the concentration of these ligands is + reduced. Because of the slow conformational change, the affinities for ligands + affecting inactivation are time dependent. A model is presented to explain + the effects of free Mg2+ and Ma-ATP on (Na-K)ATPase activity.", "venue": "Biochemistry", + "year": 1976, "referenceCount": 26, "citationCount": 25, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Medicine", + "Chemistry"], "s2FieldsOfStudy": [{"category": "Medicine", "source": "external"}, + {"category": "Chemistry", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1976-11-30", "journal": {"volume": "15 24", "pages": "\n 5280-7\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5095505", "name": "L. Josephson"}]}, {"paperId": "a42ba50dfd6939496fc0d25e5c3c3accf057c814", + "externalIds": {"MAG": "2080861877", "DOI": "10.1021/BI00684A027", "CorpusId": + 36277958, "PubMed": "1148187"}, "corpusId": 36277958, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/a42ba50dfd6939496fc0d25e5c3c3accf057c814", + "title": "Characterization of nucleotide binding sites on chloroplast coupling + factor 1.", "abstract": "A study of the equilibrium binding of ADP, 1,N6-ethenoadenosine + diphosphate, adenylyl imidodiphosphate, and 1,N6-ethenoadenylyl imidodiphosphate + to solubilized spinach chloroplast coupling factor 1 (CF1) has been carried + out. All four nucleotides were found to bind to two apparently identical \"tight\" + sites, with characteristic dissociation contants generally less than 10 muM. + The binding to these \"tight\" sites is similar in the presence of Mg2+ and + Ca2+, is stronger in 0.1 M NaC1 than in 20 mM Tris-C1, and is only slightly + altered by heat activation. The slow rate of association of ADP and 1,N6-ethenoadenosine + diphosphate at these sites rules out the possibility that they are catalytic + sites for ATPase activity on the solubilized enzyme. A third tight site for + adenylyl imidodiphosphate was found on the heat-activated enzyme. The dissociation + constant for this interaction (7.6 muM) is similar to the adenylyl imidodiphosphate + competitive inhibition constant for ATPase activity (4 muM). ADP, which inhibits + ATPase activity but is not a strong competitive inhibitor, binds only weakly + at a third site (dissociation constant greater than 70 muM). One mole of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole + reacted per mole of CF1 prevents ADP and adenylyl imidodiphosphate binding + at the \"catalytic\" site and abolishes the ATPase activity. A model is proposed + in which the \"tight\" nucleotide binding sites act as allosteric conformational + switches for the ATPase activity of solubilizedCF1.", "venue": "Biochemistry", + "year": 1975, "referenceCount": 23, "citationCount": 93, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1975-07-01", "journal": + {"volume": "14 13", "pages": "\n 2968-75\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5738308", + "name": "G. Hammes"}]}, {"paperId": "bbfdb526852c4c10aabe021b41cc3e2739458ff4", + "externalIds": {"MAG": "2031413887", "DOI": "10.1021/BI00684A028", "CorpusId": + 31588230, "PubMed": "1148188"}, "corpusId": 31588230, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/bbfdb526852c4c10aabe021b41cc3e2739458ff4", + "title": "Fluorescence energy transfer between ligand binding sites on chloroplast + coupling factor 1.", "abstract": "The method of fluorescence energy transfer + is used to measure the distance from the tight nucleotide binding sites to + the 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole reactive sites on solubilized + spinach chloroplast coupling factor 1 (CF1). The fluorescent adenine nucleotide + analogs 1,N-6-ethenoadenosine diphosphate and 1,N-6-ethenoadenylyl imidodiphosphate + were used as donors and 4-nitrobenzo-2-oxa-1,3-diazole bound to a tyrosine + group and to an amino group were used as acceptors of energy transfer. Using + three different donor-acceptor pairs, the distance measured varied from 38 + to 43 A assuming both donor sites are equidistant from the acceptor site. + A model is proposed for the location of the tight nucleotide binding sites + and the active site on the alpha and beta subunits of CF1.", "venue": "Biochemistry", + "year": 1975, "referenceCount": 16, "citationCount": 68, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Chemistry", + "source": "s2-fos-model"}, {"category": "Biology", "source": "s2-fos-model"}], + "publicationTypes": ["JournalArticle"], "publicationDate": "1975-07-01", "journal": + {"volume": "14 13", "pages": "\n 2976-81\n ", "name": "Biochemistry"}, + "authors": [{"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5738308", + "name": "G. Hammes"}]}, {"paperId": "8dacd1423377b87714687115f8287fb8555c1923", + "externalIds": {"MAG": "2068021516", "DOI": "10.1021/BI00748A014", "CorpusId": + 30213623, "PubMed": "4271561"}, "corpusId": 30213623, "publicationVenue": + {"id": "ae7a3201-e479-4666-8a93-3d35d6bf7cd1", "name": "Biochemistry", "type": + "journal", "issn": "0006-2960", "alternate_issns": ["2632-0983"], "url": "https://pubs.acs.org/journal/bichaw", + "alternate_urls": ["http://pubs.acs.org/journal/bichaw", "https://mts.intechopen.com/series/biochemistry", + "http://pubs.acs.org/journals/bichaw/index.html", "http://pubs.acs.org/journal/bichaw?cookieSet=1"]}, + "url": "https://www.semanticscholar.org/paper/8dacd1423377b87714687115f8287fb8555c1923", + "title": "Activation of beef heart mitochondrial adenosine triphosphatase + by 2,4-dinitrophenol.", "abstract": null, "venue": "Biochemistry", "year": + 1973, "referenceCount": 15, "citationCount": 57, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": ["Chemistry", + "Medicine"], "s2FieldsOfStudy": [{"category": "Chemistry", "source": "external"}, + {"category": "Medicine", "source": "external"}, {"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": ["JournalArticle"], "publicationDate": + "1973-11-20", "journal": {"volume": "12 24", "pages": "\n 4900-4\n ", + "name": "Biochemistry"}, "authors": [{"authorId": "1723755", "name": "L. Cantley"}, + {"authorId": "5738308", "name": "G. Hammes"}]}, {"paperId": "50e70f931b25f06d0d2085529580c973aede55b8", + "externalIds": {"CorpusId": 207793454}, "corpusId": 207793454, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/50e70f931b25f06d0d2085529580c973aede55b8", + "title": "Cell Metabolism Previews PI 3 K Enters Beta-Testing", "abstract": + "Adam J. Shaywitz,1,2 Kevin D. Courtney,1,3 Akash Patnaik,1,4 and Lewis C. + Cantley1,5,* 1Division of Signal Transduction 2Division of Endocrinology Beth + Israel Deaconess Medical Center, Boston, MA 02215, USA 3Department of Medical + Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA 4Division of + Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, + USA 5Department of Systems Biology, Harvard Medical School, Boston, MA 02115, + USA *Correspondence: lewis_cantley@hms.harvard.edu DOI 10.1016/j.cmet.2008.08.011", + "venue": "", "year": null, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Medicine", "source": "s2-fos-model"}], "publicationTypes": + ["Review"], "publicationDate": null, "journal": null, "authors": [{"authorId": + "4635185", "name": "A. Shaywitz"}, {"authorId": "13782167", "name": "K. Courtney"}, + {"authorId": "40501341", "name": "A. Patnaik"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "86e16b2299ef230a67506a9a93d0310a972d7763", "externalIds": + {"CorpusId": 5698342}, "corpusId": 5698342, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/86e16b2299ef230a67506a9a93d0310a972d7763", + "title": "Methionine-Labeled Proteins in CHO / IR Cells", "abstract": null, + "venue": "", "year": null, "referenceCount": 0, "citationCount": 0, "influentialCitationCount": + 0, "isOpenAccess": false, "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": + [{"category": "Biology", "source": "s2-fos-model"}], "publicationTypes": null, + "publicationDate": null, "journal": null, "authors": [{"authorId": "3978573", + "name": "N. Ruderman"}, {"authorId": "2028875", "name": "R. Kapeller"}, {"authorId": + "2104916910", "name": "Morris F. Whites"}, {"authorId": "1723755", "name": + "L. Cantley"}]}, {"paperId": "cfab756f944676f58c653d205bcf932f10fa0020", "externalIds": + {"CorpusId": 22941542}, "corpusId": 22941542, "publicationVenue": null, "url": + "https://www.semanticscholar.org/paper/cfab756f944676f58c653d205bcf932f10fa0020", + "title": "Synthesis and Activity of C 11-Modified Wortmannin Probes for PI + 3 Kinase", "abstract": "The key role played by PI3 kinase in cancer, hormone + action, and a host of other biological functions suggests that specific inhibitors + whose disposition could be ascertained in vivo would be useful in biological + research or, potentially, for imaging PI3K in a clinical setting. Wortmannin + (Wm, 1) is an inhibitor of PI3 kinase with high specificity for this enzyme. + We synthesized three modified Wm probes, a biotinylated Wm (7a), a 4-hydroxy-3-iodophenylated + Wm, which was obtained both unlabeled (7b) and labeled with 125I (8), and + a fluoresceinated Wm (7c), through modification at C-11, and evaluated their + inhibitive activity as inhibitors of PI3 kinase. Biotinylated (7a) and 4-hydroxy-3-iodophenylated + Wm\u2019s (7b) had IC50s for PI3K of 6.11 and 11.02 nM, respectively, compared + to an IC50 for Wm of 1.63 nM. Fluoresceinated Wm (7c) lost considerably more + activity than the other derivatives, with an IC50 of 64.9 nM. The 125I labeled + 4-hydroxy-3-iodophenylated Wm (8) could be detected after reaction with an + immunoprecipitate of PI3 kinase. The activity of these reporter Wm\u2019s + is discussed in relationship to earlier findings on the pharmacological activity + of Wm derivatives and the ability of inhibitors to fit into the ATP pocket + of PI3 kinase.", "venue": "", "year": null, "referenceCount": 23, "citationCount": + 2, "influentialCitationCount": 0, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}, {"category": "Chemistry", "source": "s2-fos-model"}], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "6230104", + "name": "Hushan Yuan"}, {"authorId": "145954100", "name": "Ji Luo"}, {"authorId": + "123039768", "name": "S. Field"}, {"authorId": "3127756", "name": "R. Weissleder"}, + {"authorId": "1723755", "name": "L. Cantley"}, {"authorId": "5095505", "name": + "L. Josephson"}]}, {"paperId": "d01c021f3f20c64e03e049f42e520b2921b04c78", + "externalIds": {"CorpusId": 207769406}, "corpusId": 207769406, "publicationVenue": + null, "url": "https://www.semanticscholar.org/paper/d01c021f3f20c64e03e049f42e520b2921b04c78", + "title": "Histone Methylation-Adenosylmethionine and S Influence of Threonine + Metabolism on", "abstract": null, "venue": "", "year": null, "referenceCount": + 0, "citationCount": 1, "influentialCitationCount": 0, "isOpenAccess": false, + "openAccessPdf": null, "fieldsOfStudy": null, "s2FieldsOfStudy": [], "publicationTypes": + null, "publicationDate": null, "journal": null, "authors": [{"authorId": "1397529716", + "name": "Ng Shyh\u2010Chang"}, {"authorId": "2268976", "name": "J. Locasale"}, + {"authorId": "4901222", "name": "C. Lyssiotis"}, {"authorId": "1723564", "name": + "Yuxiang Zheng"}, {"authorId": "50651504", "name": "Ren Yi Teo"}, {"authorId": + "5878690", "name": "Sutheera Ratanasirintrawoot"}, {"authorId": "2117170793", + "name": "Jin Zhang"}, {"authorId": "5073178", "name": "T. Onder"}, {"authorId": + "38764542", "name": "J. Unternaehrer"}, {"authorId": "1410084451", "name": + "Hao Zhu"}, {"authorId": "3028470", "name": "J. Asara"}, {"authorId": "2028224", + "name": "G. Daley"}, {"authorId": "1723755", "name": "L. Cantley"}]}, {"paperId": + "d3ba40f9be03277b52740056c787ecda4ca42f2c", "externalIds": {"CorpusId": 13613107}, + "corpusId": 13613107, "publicationVenue": null, "url": "https://www.semanticscholar.org/paper/d3ba40f9be03277b52740056c787ecda4ca42f2c", + "title": "Evolution of Ime 2 Phosphorylation Sites on Cdk 1 Substrates Provides + a Mechanism to Limit the Effects of the Phosphatase Cdc 14 in Meiosis", "abstract": + "Progression through meiosis in yeast is governed by the cyclin-dependent + kinase Cdk1, in concert with a related kinase called Ime2. It remains unclear + how these kinases collaborate to meet the unique demands of meiotic progression. + We demonstrate that Ime2 and Cdk1 phosphorylate an overlapping substrate set + and that the two kinases overlap functionally as inhibitors of the ubiquitin + ligase APC and replication origin licensing. Surprisingly, Ime2 phosphorylates + Cdk1 substrates at distinct phosphorylation sites that are highly resistant + to dephosphorylation by the phosphatase Cdc14. We propose that Ime2-dependent + phosphorylation of a subset of cell-cycle proteins limits the effects of Cdc14 + in meiosis.", "venue": "", "year": null, "referenceCount": 56, "citationCount": + 9, "influentialCitationCount": 1, "isOpenAccess": false, "openAccessPdf": + null, "fieldsOfStudy": null, "s2FieldsOfStudy": [{"category": "Biology", "source": + "s2-fos-model"}], "publicationTypes": null, "publicationDate": null, "journal": + null, "authors": [{"authorId": "4344976", "name": "L. Holt"}, {"authorId": + "6742227", "name": "Jessica E. Hutti"}, {"authorId": "1723755", "name": "L. + Cantley"}, {"authorId": "35719273", "name": "D. Morgan"}]}]} + + ' + headers: + Access-Control-Allow-Origin: + - '*' + Connection: + - keep-alive + Content-Length: + - '50602' + Content-Type: + - application/json + Date: + - Mon, 23 Jan 2023 17:30:59 GMT + Via: + - 1.1 098b9cbcfa96d29975715e06357bae4e.cloudfront.net (CloudFront) + X-Amz-Cf-Id: + - sUEiJoWw-A4dMzhF0XUbuxY9KmsAOUmdxac3tZe-X8XULAb1V9APeA== + X-Amz-Cf-Pop: + - GIG51-P4 + X-Cache: + - Miss from cloudfront + x-amz-apigw-id: + - fNOdGEDtPHcFQ8g= + x-amzn-Remapped-Connection: + - keep-alive + x-amzn-Remapped-Content-Length: + - '50602' + x-amzn-Remapped-Date: + - Mon, 23 Jan 2023 17:30:59 GMT + x-amzn-Remapped-Server: + - gunicorn + x-amzn-RequestId: + - d03a2c5a-e2fc-4993-9e82-e78f746b3e3d + status: + code: 200 + message: OK +version: 1 diff --git a/tests/test_semanticscholar.py b/tests/test_semanticscholar.py index 362dad9..0117142 100644 --- a/tests/test_semanticscholar.py +++ b/tests/test_semanticscholar.py @@ -199,6 +199,16 @@ def test_get_authors(self): list_of_author_names = ['E. Dijkstra', 'D. Parnas', 'I. Sommerville'] self.assertCountEqual( [item.name for item in data], list_of_author_names) + + @test_vcr.use_cassette + def test_get_author_papers(self): + data = self.sch.get_author_papers(1723755, limit=100) + self.assertEqual(data.offset, 0) + self.assertEqual(data.next, 100) + self.assertEqual(len([item for item in data]), 925) + self.assertEqual(data[0].title, 'Genetic heterogeneity and ' + 'tissue-specific patterns of tumors with multiple ' + 'PIK3CA mutations.') @test_vcr.use_cassette def test_not_found(self): @@ -259,6 +269,8 @@ def test_limit_value_exceeded(self): 'The limit parameter must be between 1 and 1000 inclusive.'), (self.sch.get_paper_references, '10.1093/mind/lix.236.433', 1001, 'The limit parameter must be between 1 and 1000 inclusive.'), + (self.sch.get_author_papers, 1723755, 1001, + 'The limit parameter must be between 1 and 1000 inclusive.'), (self.sch.search_author, 'turing', 1001, 'The limit parameter must be between 1 and 1000 inclusive.'), (self.sch.search_paper, 'turing', 101,