{"doi":"10.1016/j.tcb.2015.06.002","title":"Regulation of mTORC1 by PI3K signaling","abstract":null,"journal":"Trends in Cell Biology","year":2015,"id":687213,"datarank":1.0130156877896672,"base_score":6.75343791859778,"endowment":6.75343791859778,"self_citation_contribution":1.0130156877896672,"citation_network_contribution":0.0,"self_endowment_contribution":1.0130156877896672,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":856,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":25,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51785,"name":"Lewis C. Cantley","orcid":"0000-0002-1298-7653","position":1,"is_corresponding":false},{"id":849872,"name":"Christian C. Dibble","orcid":"0000-0002-1122-9017","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Regulation of mTORC1 by PI3K signaling","abstract":"The class I phosphoinositide 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling network directs cellular metabolism and growth. Activation of mTORC1 [composed of mTOR, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8(mLST8), 40-kDa proline-rich Akt substrate (PRAS40), and DEP domain-containing mTOR-interacting protein (DEPTOR)] depends on the Ras-related GTPases (Rags) and Ras homolog enriched in brain (Rheb) GTPase 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 tuberous sclerosis complex (TSC) complex (TSC complex) [composed of TSC1, TSC2, and Tre2-Bub2-Cdc16-1 domain family member 7 (TBC1D7)] switches on Rheb at the lysosome, where mTORC1 is activated. Integration of PI3K- and amino acid-dependent signals upstream of mTORC1 at the lysosome is detailed in a working model. A coherent understanding of the PI3K-mTORC1 network is imperative as its dysregulation has been implicated in diverse pathologies including cancer, diabetes, autism, and aging.","is_dataset_classified":null,"base_score":6.75343791859778,"endowment":6.75343791859778,"datacite_reuse_total":25,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26159692","pmcid":"PMC4734635","openalex_id":"https://openalex.org/W1804602290","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"K99-CA194314","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM041890","title":null},{"funder_name":"NCI NIH HHS","grant_id":"K99 CA194314","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01-GM041890","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM041890-29","title":"The Role of PI3K in Growth Regulation"},{"funder_name":"National Institutes of Health","grant_id":"1K99CA194314-01","title":"ROLE OF VITAMIN B5 AND COENZYME A METABOLISM IN PI3K DRIVEN TUMORIGENESIS"}],"total_grants":6,"fwci":30.2223,"citation_percentile":0.99846083,"influential_citations":0,"citation_trend":[{"year":2015,"count":9},{"year":2016,"count":62},{"year":2017,"count":80},{"year":2018,"count":68},{"year":2019,"count":77},{"year":2020,"count":84},{"year":2021,"count":92},{"year":2022,"count":95},{"year":2023,"count":78},{"year":2024,"count":111},{"year":2025,"count":70},{"year":2026,"count":30}],"oa_status":"green","license":"Elsevier TDM","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4734635","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4734635","host_type":"repository"},{"url":"https://doi.org/10.1016/j.tcb.2015.06.002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26159692","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc4734635?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.1016/j.tcb.2015.06.002","host_type":""}],"fields_of_study":["PI3K/AKT/mTOR signaling in cancer","Tuberous Sclerosis Complex Research","Mast cells and histamine","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Mechanistic Target of Rapamycin Complex 1","Animals","Autistic Disorder","Diabetes Mellitus","Humans","Insulin","Lysosomes","Signal Transduction","Phosphatidylinositol 3-Kinases","Feedback, Physiological","Multiprotein Complexes","Intracellular Signaling Peptides and Proteins","TOR Serine-Threonine Kinases"],"keywords":["RHEB","mTORC1","PI3K/AKT/mTOR pathway","Biology","TSC1","TSC2","mTORC2","Cell biology","Protein kinase B","Mechanistic target of rapamycin","RPTOR","Signal transduction","GTPase","Small GTPase","Insulin","Lysosome","Raptor","Rag","Feedback, Physiological","TOR Serine-Threonine Kinases","Intracellular Signaling Peptides and Proteins","Mechanistic Target of Rapamycin Complex 1","Phosphatidylinositol 3-Kinases","Multiprotein Complexes","Diabetes Mellitus","Animals","Humans","Autistic Disorder","Lysosomes"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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