Rheb GTP酶是TSC2 GAP活性的直接靶点，并调节mTOR信号传导。
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.
作者信息
Inoki Ken, Li Yong, Xu Tian, Guan Kun-Liang
机构信息
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
出版信息
Genes Dev. 2003 Aug 1;17(15):1829-34. doi: 10.1101/gad.1110003. Epub 2003 Jul 17.
Abstract
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.
摘要
结节性硬化症（TSC）是一种由TSC1或TSC2基因突变引起的遗传性疾病。TSC1和TSC2基因产物形成一个功能复合物，并抑制S6K和4EBP1的磷酸化。TSC1/TSC2的这些功能可能由mTOR介导。在此我们报告，TSC2是一种针对Rheb（一种Ras家族GTP酶）的GTP酶激活蛋白（GAP）。Rheb刺激S6K和4EBP1的磷酸化。Rheb的这一功能被雷帕霉素和显性负性mTOR所阻断。Rheb刺激mTOR的磷酸化，并在响应营养物质和细胞能量状态时对S6K和4EBP1的调节中起重要作用。我们的数据表明，Rheb在TSC1/TSC2的下游和mTOR的上游起作用，以调节细胞生长。
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