Brief Communication abstract
Nature Cell Biology 5, 578 - 581 (2003)
Published online: 27 May 2003 | doi:10.1038/ncb999
Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
Yong Zhang1,3,4, Xinsheng Gao1,4, Leslie J. Saucedo2, Binggen Ru3, Bruce A. Edgar2 & Duojia Pan1
Mutations in the TSC1 or TSC2 genes cause tuberous sclerosis, a benign tumour syndrome in humans1, 2. Tsc2 possesses a domain that shares homology with the GTPase-activating protein (GAP) domain of Rap1-GAP2, 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.
- Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9040, USA.
- Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
- Department of Biochemistry, Peking University, Beijing 100871, China.
- These authors contributed equally to this work.
Correspondence to: Duojia Pan1 e-mail: dpan@mednet.swmed.edu
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REVIEWS NEWS AND VIEWS RESEARCH |
