ArticleGenes & development2003
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.
Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 980 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
980 citing papers in PubMed, 1,900 citations in OpenAlex.
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- Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder.iScience · 2026Article
- Review
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.Nature communications · 2026Article
- Multi-omics analysis reveals the effects of Codonopsis pilosula polysaccharides on the skeletal muscle development of Sansui ducks during the embryonic stage.Poultry science · 2026Article
- An integrated, scaled approach to resolve TSC2 variants of uncertain significance.Nature communications · 2026Article
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Dual regulatory roles of CPT1C in chronic stress-induced depression-related outcomes.Molecular psychiatry · 2026Article
- YIF1A activates mTORC1 signaling to promote cellular senescence.Cell death & disease · 2026Article
- NF1 and SPRED1/2 cooperate through RAS-MAPK-independent functions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Enterococcus faecalis Extracellular Vesicles Deliver the Bacterial GTPase Obg to Hijack mTOR Signalling in Hepatocellular Carcinoma.Journal of extracellular vesicles · 2026Article
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Targeting the GSK-3β/mTOR axis to overcome chemoresistance in gestational choriocarcinoma: molecular mechanisms and therapeutic opportunities.Cancer chemotherapy and pharmacology · 2026Review
- Overactive Neuronal eEF2K/eEF2 signaling is associated with cognitive impairment and apathy-like behavior.Molecular psychiatry · 2026Article
- Correlation of the differential expression of PIK3R1 and its spliced variant, p55α, in pan-cancer.Molecular oncology · 2026Article
- The pivotal role of mitochondria in the pathogenesis and treatment of liver failure: a comprehensive review.Molecular and cellular biochemistry · 2026Review
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
920 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR. Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status. Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.