GβL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR
GβL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR
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DOI：
10.1016/s1097-2765(03)00114-x
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发表时间：
2003-04-01
期刊：
影响因子：
16
通讯作者：
Sabatini, DM
中科院分区：
文献类型：
--
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
MTOR和RAPTOR是信号通路的组成部分，该途径可根据养分和生长因子来调节哺乳动物细胞的生长。在这里，我们确定了该途径的成员，该途径是一种称为Gbetal的蛋白质，该蛋白质与MTOR的激酶结构结合并稳定猛禽与MTOR的相互作用。像MTOR和RAPTOR一样，Gbetal也参与了营养因子介导的信号传导，以S6K1（MTOR的下游效应子）和细胞大小的控制。 Gbetal对MTOR的结合强烈刺激MTOR对S6K1和4E-BP1的激酶活性，这种效应是由Raptor与MTOR的稳定相互作用逆转的。有趣的是，只有在含有gbetal的复合物中，营养素和雷帕霉素才能调节MTOR和猛禽之间的关联。因此，我们提出对GBETAL和RAPTOR介导的相互作用的相反影响调节MTOR途径。
mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors. Here, we identify a member of this pathway, a protein named GbetaL that binds to the kinase domain of mTOR and stabilizes the interaction of raptor with mTOR. Like mTOR and raptor, GbetaL participates in nutrient-and growth factor-mediated signaling to S6K1, a downstream effector of mTOR, and in the control of cell size. The binding of GbetaL to mTOR strongly stimulates the kinase activity of mTOR toward S6K1 and 4E-BP1, an effect reversed by the stable interaction of raptor with mTOR. Interestingly, nutrients and rapamycin regulate the association between mTOR and raptor only in complexes that also contain GbetaL. Thus, we propose that the opposing effects on mTOR activity of the GbetaL- and raptor-mediated interactions regulate the mTOR pathway.