Kim Do-Hyung, Sarbassov D D, Ali Siraj M, King Jessie E, Latek Robert R, Erdjument-Bromage Hediye, Tempst Paul, Sabatini David M
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Cell. 2002 Jul 26;110(2):163-75. doi: 10.1016/s0092-8674(02)00808-5.
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.
mTOR/RAFT1/FRAP是免疫抑制药物雷帕霉素的作用靶点，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。我们报告称，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通路中至少具有两个作用。Raptor在营养刺激的下游效应器S6K1信号传导、细胞大小维持和mTOR蛋白表达中具有正向作用。Raptor与mTOR的结合也对mTOR激酶活性产生负调节作用。抑制该通路的条件，如营养剥夺和线粒体解偶联，会稳定mTOR-raptor结合并抑制mTOR激酶活性。我们提出，raptor是mTOR通路中缺失的一个组成部分，它通过与mTOR结合，响应营养水平调节细胞大小。
