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首页> 外文期刊>Molecular and Cellular Biology >Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase.
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Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase.

机译：胰岛素刺激蛋白质合成，真核翻译起始因子4E磷酸化和PHAS-1磷酸化需要胰岛素受体底物1和磷脂酰肌醇3激酶。

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Insulin rapidly stimulates protein synthesis in a wide variety of tissues. This stimulation is associated with phosphorylation of several translational initiation and elongation factors, but little is known about the signaling pathways to these events. To study these pathways, we have used a myeloid progenitor cell line (32D) which is dependent on interleukin 3 but insensitive to insulin because of the very low levels of insulin receptor (IR) and the complete lack of insulin receptor substrate (IRS)-signaling proteins (IRS-1 and IRS-2). Expression of more IR permits partial stimulation of mitogen-activated protein kinase by insulin, and expression of IRS-1 alone mediates insulin stimulation of the 70-kDa S6 kinase (pp70S6K) by the endogenous IR. However, expression of both IR and IRS-1 is required for stimulation of protein synthesis. Moreover, this effect requires activation of phosphatidylinositol 3-kinase (PI3K), as determined by wortmannin inhibition and the use of an IRS-1 variant lacking all Tyr residues except those which activate PI3K. Stimulation of general protein synthesis does not involve activation by IRS-1 of GRB-2-SOS-p21ras or SH-PTP2, since IRS-1 variants lacking the SH2-binding Tyr residues for these proteins are fully active. Nor does it involve pp70S6K, since rapamycin, while strongly inhibiting the synthesis of a small subset of growth-regulated proteins, only slightly inhibits total protein synthesis. Recruitment of mRNAs to the ribosome is enhanced by phosphorylation of eIF4E, the cap-binding protein, and PHAS-I, a protein that specifically binds eIF4E. The behavior of cell lines containing IRS-1 variants and inhibition by wortmannin and rapamycin indicate that the phosphorylation of both proteins requires IRS-1-mediated stimulation of PI3K and pp70S6K but not mitogen-activated protein kinase or SH-PTP2.
机译：胰岛素可迅速刺激多种组织中的蛋白质合成。这种刺激与几种翻译起始和延伸因子的磷酸化有关，但对这些事件的信号传导途径知之甚少。为了研究这些途径，我们使用了依赖于白介素3但对胰岛素不敏感的髓样祖细胞系（32D），因为其胰岛素受体（IR）的水平非常低，并且完全缺乏胰岛素受体底物（IRS），信号蛋白（IRS-1和IRS-2）。表达更多的IR可以通过胰岛素部分刺激促分裂原活化的蛋白激酶，而单独的IRS-1的表达可以通过内源性IR介导70 kDa S6激酶（pp70S6K）的胰岛素刺激。但是，IR和IRS-1的表达都需要刺激蛋白质的合成。此外，这种作用需要激活磷脂酰肌醇3-激酶（PI3K），这是由渥曼青霉素抑制作用和使用IRS-1变体（除激活PI3K的残基之外）缺乏所有Tyr残基确定的。普通蛋白质合成的刺激不涉及GRB-2-SOS-p21ras或SH-PTP2的IRS-1激活，因为缺少这些蛋白的SH2结合Tyr残基的IRS-1变体是完全活性的。 pp70S6K也不涉及pp70S6K，因为雷帕霉素在强烈抑制一小部分受生长调节的蛋白质的合成的同时，仅略微抑制了总蛋白质的合成。通过帽结合蛋白eIF4E和特异性结合eIF4E的蛋白质PHAS-1的磷酸化，可增强mRNA向核糖体的募集。含有IRS-1变体的细胞系的行为以及渥曼青霉素和雷帕霉素的抑制作用表明，这两种蛋白的磷酸化都需要IRS-1介导的PI3K和pp70S6K的刺激，而无需丝裂原激活的蛋白激酶或SH-PTP2。

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