Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin
Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin
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DOI：
10.1126/science.277.5322.99
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发表时间：
1997-07-04
期刊：
影响因子：
56.9
通讯作者：
Abraham, RT
中科院分区：
文献类型：
--
作者：
Brunn, GJ;Hudson, CC;Abraham, RT
免疫抑制剂雷帕霉素通过抑制哺乳动物雷帕霉素靶标（mTOR）的功能来干扰淋巴和其它细胞类型中的G（1）期进展; mTOR被确定为将促有丝分裂刺激与真核起始因子（eIF）-4E-结合蛋白PHAS-I的磷酸化偶联的信号传导途径中的末端激酶。mTOR的雷帕霉素敏感性蛋白激酶活性是胰岛素刺激的人胚肾细胞中PHAS-I磷酸化所必需的。mTOR在体外磷酸化丝氨酸和苏氨酸残基上的PHAS-I，并且这些修饰抑制PHAS-I与eIF-4 E的结合。这些研究确定了mTOR在翻译控制中的作用，并进一步深入了解了雷帕霉素抑制哺乳动物细胞G（1）期进展的机制。
The immunosuppressant rapamycin interferes with G(1)-phase progression in lymphoid and other cell types by inhibiting the function; of the mammalian target of rapamycin (mTOR), mTOR was determined to be a terminal kinase in a signaling pathway that couples mitogenic stimulation to the phosphorylation of the eukaryotic initiation factor (eIF)-4E-binding protein, PHAS-I. The rapamycin-sensitive protein kinase activity of mTOR was required for phosphorylation of PHAS-I in insulin-stimulated human embryonic kidney cells. mTOR phosphorylated PHAS-I on serine and threonine residues in vitro, and these modifications inhibited the binding of PHAS-I to eIF-4E. These studies define a role for mTOR in translational control and offer further insights into the mechanism whereby rapamycin inhibits G(1)-phase progression in mammalian cells.