Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling
Top Cited Papers
Open Access
- 17 July 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (15) , 1829-1834
- https://doi.org/10.1101/gad.1110003
Abstract
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.Keywords
This publication has 36 references indexed in Scilit:
- Tsc tumour suppressor proteins antagonize amino-acid–TOR signallingNature Cell Biology, 2002
- TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signallingNature Cell Biology, 2002
- Tuberin Regulates p70 S6 Kinase Activation and Ribosomal Protein S6 PhosphorylationJournal of Biological Chemistry, 2002
- Phosphatidic Acid-Mediated Mitogenic Activation of mTOR SignalingScience, 2001
- Mammalian TOR: A Homeostatic ATP SensorScience, 2001
- Mechanisms of size controlCurrent Opinion in Genetics & Development, 2001
- eIF4 Initiation Factors: Effectors of mRNA Recruitment to Ribosomes and Regulators of TranslationAnnual Review of Biochemistry, 1999
- Identification of Tuberin, the Tuberous Sclerosis-2 Product. TUBERIN POSSESSES SPECIFIC Rap1GAP ACTIVITYJournal of Biological Chemistry, 1995
- Identification and characterization of the tuberous sclerosis gene on chromosome 16Cell, 1993
- Phenotypes of the Tuberous Sclerosis Complex with a Revision of Diagnostic CriteriaAnnals of the New York Academy of Sciences, 1991