MTOR interacts with Raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
MTOR interacts with Raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
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DOI：
10.1016/s0092-8674(02)00808-5
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发表时间：
2002-07-26
期刊：
影响因子：
64.5
通讯作者：
Sabatini, DM
中科院分区：
文献类型：
--
作者：
Kim, DH;Sarbassov, DD;Sabatini, DM
mTOR/RAFT1/FRAP 是免疫抑制药物雷帕霉素的靶点，也是调节细胞生长的营养和激素敏感信号通路的核心组成部分。我们报告说，mTOR 与 raptor 形成化学计量复合物，raptor 是一种进化上保守的蛋白质，在 mTOR 通路中至少有两个作用。 Raptor 在向下游效应器 S6K1 发出营养刺激信号、维持细胞大小和 mTOR 蛋白表达方面发挥积极作用。 raptor 与 mTOR 的关联也会负向调节 mTOR 激酶活性。抑制该通路的条件，例如营养剥夺和线粒体解偶联，可以稳定 mTOR-raptor 关联并抑制 mTOR 激酶活性。我们认为 raptor 是 mTOR 通路中缺失的一个组成部分，它通过与 mTOR 的关联来调节细胞大小以响应营养水平。
mTOR/RAFT1/FRAP is the target of the immunosuppressive drug rapamycin and the central component of a nutrient- and hormone-sensitive signaling pathway that regulates cell growth. We report that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway. Raptor has a positive role in nutrient-stimulated signaling to the downstream effector S6K1, maintenance of cell size, and mTOR protein expression. The association of raptor with mTOR also negatively regulates the mTOR kinase activity. Conditions that repress the pathway, such as nutrient deprivation and mitochondrial uncoupling, stabilize the mTOR-raptor association and inhibit mTOR kinase activity. We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels.