{"doi":"10.1042/bj20080281","title":"The TSC1–TSC2 complex: a molecular switchboard controlling cell growth","abstract":"<jats:p>TSC1 and TSC2 are the tumour-suppressor genes mutated in the tumour syndrome TSC (tuberous sclerosis complex). Their gene products form a complex that has become the focus of many signal transduction researchers. The TSC1–TSC2 (hamartin–tuberin) complex, through its GAP (GTPase-activating protein) activity towards the small G-protein Rheb (Ras homologue enriched in brain), is a critical negative regulator of mTORC1 (mammalian target of rapamycin complex 1). As mTORC1 activity controls anabolic processes to promote cell growth, it is exquisitely sensitive to alterations in cell growth conditions. Through numerous phosphorylation events, the TSC1–TSC2 complex has emerged as the sensor and integrator of these growth conditions, relaying signals from diverse cellular pathways to properly modulate mTORC1 activity. In the present review we focus on the molecular details of TSC1–TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1.</jats:p>","journal":"Biochemical Journal","year":2008,"id":652062,"datarank":1.0695147765188369,"base_score":7.130098510125578,"endowment":7.130098510125578,"self_citation_contribution":1.0695147765188369,"citation_network_contribution":0.0,"self_endowment_contribution":1.0695147765188369,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1248,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"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":1700851,"name":"Brendan D. Manning","orcid":null,"position":1,"is_corresponding":false},{"id":1700850,"name":"Jingxiang Huang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The TSC1–TSC2 complex: a molecular switchboard controlling cell growth","abstract":"<jats:p>TSC1 and TSC2 are the tumour-suppressor genes mutated in the tumour syndrome TSC (tuberous sclerosis complex). Their gene products form a complex that has become the focus of many signal transduction researchers. The TSC1–TSC2 (hamartin–tuberin) complex, through its GAP (GTPase-activating protein) activity towards the small G-protein Rheb (Ras homologue enriched in brain), is a critical negative regulator of mTORC1 (mammalian target of rapamycin complex 1). As mTORC1 activity controls anabolic processes to promote cell growth, it is exquisitely sensitive to alterations in cell growth conditions. Through numerous phosphorylation events, the TSC1–TSC2 complex has emerged as the sensor and integrator of these growth conditions, relaying signals from diverse cellular pathways to properly modulate mTORC1 activity. In the present review we focus on the molecular details of TSC1–TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1.</jats:p>","is_dataset_classified":null,"base_score":7.130098510125578,"endowment":7.130098510125578,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18466115","pmcid":"PMC2735030","openalex_id":"https://openalex.org/W1993431258","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P01 CA120964","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P01-CA120964","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01-CA122617","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R01 CA122617","title":null}],"total_grants":4,"fwci":35.695,"citation_percentile":0.99922197,"influential_citations":0,"citation_trend":[{"year":2012,"count":73},{"year":2013,"count":72},{"year":2014,"count":70},{"year":2015,"count":83},{"year":2016,"count":66},{"year":2017,"count":79},{"year":2018,"count":75},{"year":2019,"count":66},{"year":2020,"count":87},{"year":2021,"count":86},{"year":2022,"count":81},{"year":2023,"count":68},{"year":2024,"count":54},{"year":2025,"count":57},{"year":2026,"count":17}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2735030","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2735030","host_type":"repository"},{"url":"https://portlandpress.com/biochemj/article-pdf/412/2/179/655105/bj4120179.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj20080281","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18466115","host_type":"repository"}],"fields_of_study":["Tuberous Sclerosis Complex Research","PI3K/AKT/mTOR signaling in cancer","Mast cells and histamine"],"mesh_terms":["Ras Homolog Enriched in Brain Protein","Tuberous Sclerosis Complex 1 Protein","Tuberous Sclerosis Complex 2 Protein","Amino Acid Sequence","Animals","Cell Cycle","Humans","Insulin","Insulin-Like Growth Factor I","Molecular Sequence Data","Neuropeptides","Protein Kinases","Transcription Factors","Signal Transduction","Genes, Tumor Suppressor","Sequence Alignment","Ribosomal Protein S6 Kinases","Monomeric GTP-Binding Proteins","Tumor Suppressor Proteins","Intercellular Signaling Peptides and Proteins","Cell Growth Processes","TOR Serine-Threonine Kinases"],"keywords":["RHEB","TSC1","TSC2","mTORC1","Cell biology","Biology","Tuberous sclerosis","Cell growth","GTPase","Small GTPase","Signal transduction","Phosphorylation","Regulator","Mechanistic target of rapamycin","PI3K/AKT/mTOR pathway","Cancer research","Gene","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T11:46:32.436125Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}