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

624 Citations (Scopus)

Abstract

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
Volume5
Issue number6
DOIs
StatePublished - Jun 1 2003

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Tumor Suppressor Proteins
GTPase-Activating Proteins
Tuberous Sclerosis
Brain
Monomeric GTP-Binding Proteins
GTP Phosphohydrolases
Point Mutation
Neoplasms
Mutation
Genes
Protein Domains

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. / Zhang, Yong; Gao, Xinsheng; Saucedo, Leslie J.; Ru, Binggen; Edgar, Bruce A.; Pan, Duojia.

In: Nature cell biology, Vol. 5, No. 6, 01.06.2003, p. 578-581.

Research output: Contribution to journalArticle

Zhang, Yong ; Gao, Xinsheng ; Saucedo, Leslie J. ; Ru, Binggen ; Edgar, Bruce A. ; Pan, Duojia. / Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. In: Nature cell biology. 2003 ; Vol. 5, No. 6. pp. 578-581.
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