{"doi":"10.1038/ncb999","title":"Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins","abstract":null,"journal":"Nature Cell Biology","year":2003,"id":649877,"datarank":1.0259214657343265,"base_score":6.839476438228843,"endowment":6.839476438228843,"self_citation_contribution":1.0259214657343265,"citation_network_contribution":0.0,"self_endowment_contribution":1.0259214657343265,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":933,"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":340632,"name":"Xinsheng Gao","orcid":null,"position":1,"is_corresponding":false},{"id":1694329,"name":"Leslie J. Saucedo","orcid":null,"position":2,"is_corresponding":false},{"id":1694332,"name":"Binggen Ru","orcid":null,"position":3,"is_corresponding":false},{"id":596058,"name":"Bruce A. Edgar","orcid":"0000-0002-3383-2044","position":4,"is_corresponding":false},{"id":334176,"name":"Duojia Pan","orcid":"0000-0003-2890-4645","position":5,"is_corresponding":false},{"id":1043077,"name":"Yong Zhang","orcid":"0000-0001-8765-7037","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins","abstract":"Mutations in the TSC1 or TSC2 genes cause tuberous sclerosis, a benign tumour syndrome in humans. Tsc2 possesses a domain that shares homology with the GTPase-activating protein (GAP) domain of Rap1-GAP, suggesting that a GTPase might be the physiological target of Tsc2. Here we show that the small GTPase Rheb (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro. Point mutations in the GAP domain of Tsc2 disrupted its ability to regulate Rheb without affecting the ability of Tsc2 to form a complex with Tsc1. Our studies identify Rheb as a molecular target of the TSC tumour suppressors.","is_dataset_classified":null,"base_score":6.839476438228843,"endowment":6.839476438228843,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12771962","pmcid":null,"openalex_id":"https://openalex.org/W2023819606","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM62323","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM20590","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM51186","title":null},{"funder_name":"National Institutes of Health","grant_id":"2R01GM051186-06","title":"GROWTH CONTROL IN THE DROSOPHILA WING"},{"funder_name":"National Institutes of Health","grant_id":"5F32GM020590-02","title":"IDENTIFICATION OF NOVEL EFFECTORS OF CYCLIN D FUNCTION"}],"total_grants":5,"fwci":30.9472,"citation_percentile":0.99900929,"influential_citations":0,"citation_trend":[{"year":2012,"count":50},{"year":2013,"count":47},{"year":2014,"count":27},{"year":2015,"count":44},{"year":2016,"count":34},{"year":2017,"count":32},{"year":2018,"count":36},{"year":2019,"count":22},{"year":2020,"count":43},{"year":2021,"count":33},{"year":2022,"count":25},{"year":2023,"count":29},{"year":2024,"count":18},{"year":2025,"count":20},{"year":2026,"count":6}],"oa_status":"closed","license":"Springer TDM","oa_locations":[{"url":"http://www.nature.com/articles/ncb999.pdf","host_type":"publisher"},{"url":"http://www.nature.com/articles/ncb999","host_type":"publisher"},{"url":"https://doi.org/10.1038/ncb999","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12771962","host_type":"repository"},{"url":"https://soundideas.pugetsound.edu/faculty_pubs/1031","host_type":"repository"},{"url":"https://dx.doi.org/10.1038/ncb999","host_type":""}],"fields_of_study":["Tuberous Sclerosis Complex Research","Mast cells and histamine","PI3K/AKT/mTOR signaling in cancer","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Ras Homolog Enriched in Brain Protein","Tuberous Sclerosis Complex 1 Protein","Tuberous Sclerosis Complex 2 Protein","Animals","Drosophila melanogaster","Glutathione Transferase","Neuropeptides","Protein Kinases","Proteins","Recombinant Fusion Proteins","Repressor Proteins","Tuberous Sclerosis","Gene Expression Regulation, Fungal","Genes, Suppressor","Point Mutation","GTP-Binding Proteins","Phosphatidylinositol 3-Kinases","Ribosomal Protein S6 Kinases","Monomeric GTP-Binding Proteins","GTPase-Activating Proteins","Tumor Suppressor Proteins","Drosophila Proteins","TOR Serine-Threonine Kinases","In Vitro Techniques"],"keywords":["RHEB","TSC1","TSC2","Small GTPase","GTPase","Tuberous sclerosis","GTPase-activating protein","Biology","Cell biology","Cancer research","Signal transduction","mTORC1","PI3K/AKT/mTOR pathway","Pathology","Medicine","G protein","Recombinant Fusion Proteins","Ribosomal Protein S6 Kinases","TOR Serine-Threonine Kinases","GTPase-Activating Proteins","Neuropeptides","Proteins","In Vitro Techniques","Repressor Proteins","Phosphatidylinositol 3-Kinases","Drosophila melanogaster","GTP-Binding Proteins","Gene Expression Regulation, Fungal","Animals","Drosophila Proteins","Point Mutation","Ras Homolog Enriched in Brain Protein","Genes, Suppressor","Protein Kinases","Glutathione Transferase","Monomeric GTP-Binding Proteins"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T04:27:35.409729Z","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":[]}