Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

被引：1445

作者：

Inoki, K

Li, Y

Xu, T

Guan, KL ^{[1
]}

机构：

[1] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Inst Gerontol, Ann Arbor, MI 48109 USA

[3] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06536 USA

来源：

GENES & DEVELOPMENT | 2003年 / 17卷 / 15期

关键词：

TSC2; Rheb; mTOR; S6K; GAP; tuberous sclerosis complex;

D O I：

10.1101/gad.1110003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. 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.

引用

页码：1829 / 1834

页数：6

共 34 条

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