Signal transduction pathways involved in the regulation of protein synthesis by insulin in L6 myoblasts
Signal transduction pathways involved in the regulation of protein synthesis by insulin in L6 myoblasts
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DOI：
10.1152/ajpcell.1998.274.1.c221
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发表时间：
1998-01-01
影响因子：
5.5
通讯作者：
Jefferson, LS
中科院分区：
文献类型：
--
作者：
Kimball, SR;Horetsky, RL;Jefferson, LS
研究了参与胰岛素翻译作用的三种蛋白的磷酸化状态，即70-kDa核糖体蛋白S6激酶（p70(S6k)）、真核起始因子（eIF） 4E和eIF-4E结合蛋白4E- bp1。在培养的L6成肌细胞中，添加胰岛素引起蛋白质合成的刺激，这一作用被磷脂酰肌苷-3- oh激酶（wortmannin）、p70(S6k)（雷帕霉素）和丝裂原活化蛋白激酶（MAP激酶）激酶（PD-98059）的抑制剂阻断。蛋白质合成的刺激伴随着p70（S6k）磷酸化的增加，这一作用被雷帕霉素和wortmannin阻断，但PD-98059不阻断。胰岛素引起eIF-4E的去磷酸化，这一作用似乎是由p70（S6k）途径介导的。胰岛素也刺激了4E-BP1的磷酸化以及4E-BP1的解离。eIF-4E复杂。雷帕霉素和沃特曼宁完全阻断了胰岛素诱导的4E-BP1磷酸化变化以及4E-BP1和eIF-4E的关联；PD-98059对这两个参数都没有影响。最后，胰岛素刺激活性eIF-4G的形成。eIF-4E复合物，任何抑制剂都无法阻止这种效应。总的来说，结果表明胰岛素刺激L6成肌细胞的蛋白质合成部分是通过利用p70（S6k）和MAP激酶信号转导途径。
The phosphorylation states of three proteins implicated in the action of insulin on translation were investigated, i.e., 70-kDa ribosomal protein S6 kinase (p70(S6k)), eukaryotic initiation factor (eIF) 4E, and the eIF-4E binding protein 4E-BP1. Addition of insulin caused a stimulation of protein synthesis in L6 myoblasts in culture, an effect that was blocked by inhibitors of phosphatidylinositide-3-OH kinase (wortmannin), p70(S6k) (rapamycin), and mitogen-activated protein kinase (MAP kinase) kinase (PD-98059). The stimulation of protein synthesis was accompanied by increased phosphorylation of p70(S6k), an effect that was blocked by rapamycin and wortmannin but not PD-98059. Insulin caused dephosphorylation of eIF-4E, an effect that appeared to be mediated by the p70(S6k) pathway. Insulin also stimulated phosphorylation of 4E-BP1 as well as dissociation of the 4E-BP1 . eIF-4E complex. Both rapamycin and wortmannin completely blocked the insulin-induced changes in 4E-BP1 phosphorylation and association of 4E-BP1 and eIF-4E; PD-98059 had no effect on either parameter. Finally, insulin stimulated formation of the active eIF-4G . eIF-4E complex, an effect that was not prevented by any of the inhibitors. Overall, the results suggest that insulin stimulates protein synthesis in L6 myoblasts in part through utilization of both the p70(S6k) and MAP kinase signal transduction pathways.