Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Copyright policy )Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in eitherTSC1orTSC2. 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.
- University of Michigan–Flint United States
- Yale University United States
- University of Michigan–Ann Arbor United States
- Howard Hughes Medical Institute United States
Antibiotics, Antineoplastic, Dose-Response Relationship, Drug, Hydrolysis, Neuropeptides, Proteins, Models, Biological, Cell Line, GTP Phosphohydrolases, Protein Structure, Tertiary, Protein Biosynthesis, Mutation, Humans, Guanosine Triphosphate, Phosphorylation, Protein Kinases, Cell Division, Genes, Dominant, Monomeric GTP-Binding Proteins, Plasmids, Protein Binding
Antibiotics, Antineoplastic, Dose-Response Relationship, Drug, Hydrolysis, Neuropeptides, Proteins, Models, Biological, Cell Line, GTP Phosphohydrolases, Protein Structure, Tertiary, Protein Biosynthesis, Mutation, Humans, Guanosine Triphosphate, Phosphorylation, Protein Kinases, Cell Division, Genes, Dominant, Monomeric GTP-Binding Proteins, Plasmids, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).2K popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 0.1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 0.1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 0.1%
Citations provided by BIP!Popularity provided by BIP!