Rheb的开关I区域对其与FKBP38的相互作用至关重要。
The switch I region of Rheb is critical for its interaction with FKBP38.
作者信息
Ma Dongzhu, Bai Xiaochun, Guo Shuguang, Jiang Yu
机构信息
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
出版信息
J Biol Chem. 2008 Sep 19;283(38):25963-70. doi: 10.1074/jbc.M802356200. Epub 2008 Jul 25.
Abstract
The Ras-like small GTPase Rheb is an upstream activator of the mammalian target of rapamycin (mTOR). It has recently been shown that Rheb activates mTOR by binding to its endogenous inhibitor FKBP38 and preventing it from association with mTOR. The interaction of Rheb with FKBP38 is controlled by its guanine nucleotide binding states, which are responsive to growth factor and amino acid conditions. In this study, we show that Rheb interacts with FKBP38 through a section within its switch I region that is equivalent to the effector domain of other Ras-like small GTPases. We find that the ability for Rheb to interact with FKBP38 correlates with its activity for mTOR activation. Our findings suggest that FKBP38 is a bona fide effector of Rheb and that the ability to interact with FKBP38 is important for Rheb as an activator of mTOR.
摘要
类Ras小GTP酶Rheb是哺乳动物雷帕霉素靶蛋白（mTOR）的上游激活剂。最近有研究表明，Rheb通过与内源性抑制剂FKBP38结合并阻止其与mTOR结合来激活mTOR。Rheb与FKBP38的相互作用受其鸟嘌呤核苷酸结合状态的控制，该状态对生长因子和氨基酸条件有反应。在本研究中，我们表明Rheb通过其开关I区域内一个与其他类Ras小GTP酶的效应结构域等效的片段与FKBP38相互作用。我们发现Rheb与FKBP38相互作用的能力与其激活mTOR的活性相关。我们的研究结果表明，FKBP38是Rheb真正的效应分子，且与FKBP38相互作用的能力对作为mTOR激活剂的Rheb很重要。
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