Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins

Yong Zhang, Xinsheng Gao, Leslie J. Saucedo, Binggen Ru, Bruce A. Edgar, Duojia Pan

Research output: Contribution to journalArticle

628 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)578-581
Number of pages4
JournalNature Cell Biology
Issue number6
Publication statusPublished - Jun 1 2003


ASJC Scopus subject areas

  • Cell Biology

Cite this