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首页> 外文期刊>The Biochemical Journal >BOTH RAPAMYCIN-SENSITIVE AND -INSENSITIVE PATHWAYS ARE INVOLVED IN THE PHOSPHORYLATION OF THE INITIATION FACTOR-4E-BINDING PROTEIN (4E-BP1) IN RESPONSE TO INSULIN IN RAT EPIDIDYMAL FAT-CELLS
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BOTH RAPAMYCIN-SENSITIVE AND -INSENSITIVE PATHWAYS ARE INVOLVED IN THE PHOSPHORYLATION OF THE INITIATION FACTOR-4E-BINDING PROTEIN (4E-BP1) IN RESPONSE TO INSULIN IN RAT EPIDIDYMAL FAT-CELLS

机译：对大鼠表皮脂肪细胞中胰岛素的起效作用的4'-BP1起始蛋白磷酸化都涉及雷帕霉素的敏感性和敏感性通路。

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There is mounting evidence that in fat and other insulin-sensitive cells activation of protein synthesis may involve the dissociation of a protein (4E-BP1) from eukaryotic initiation factor (eIF)-4E thus allowing formation of the eIF-4F complex. This study compares the effects of insulin and epidermal growth factor (EGF) on the phosphorylation of 4E-BP1 in fat-cells (followed by gel-shift assays and incorporation of P-32) and on its association with eIF-4E. Several lines of evidence suggest that mitogen-activated protein kinase (MAP kinase) is not involved in these effects of insulin. Insulin causes much more extensive phosphorylation and dissociation of 4E-BP1 from eIF-4E than EGF, although EGF activates MAP kinase to a much greater extent than insulin, Moreover, MAP kinase does not phosphorylate 4E-BP1 when it is complexed with eIF-4E. In contrast, insulin activates the 40S ribosomal protein S6 kinase (p70(S6K)) 18-fold compared with a 2-fold activation by EGF, and the time course of this activation is similar to the phosphorylation and dissociation of 4E-BP1. Rapamycin, a specific inhibitor of the activation of this latter kinase, inhibits dissociation of 4E-BP1 from eIF-4E in cells incubated with insulin but reveals a phosphorylated form of 4E-BP1 which remains bound to eIF-4E. It is concluded that in rat epididymal fat-cells, the effects of insulin on 4E-BP1 involves multiple phosphorylation events. One phosphorylation event is rapamycin-insensitive, occurs only on bound 4E-BP1 and does not initiate dissociation. The second event does result in dissociation and is blocked by rapamycin, suggesting that the p70(S6K) Signalling pathway is involved: p70(S6K) itself is probably not involved directly as this kinase does not phosphorylate 4E-BP1 in vitro.
机译：越来越多的证据表明，在脂肪和其他胰岛素敏感性细胞中，蛋白质合成的激活可能涉及蛋白质（4E-BP1）与真核起始因子（eIF）-4E的解离，从而形成eIF-4F复合物。这项研究比较了胰岛素和表皮生长因子（EGF）对脂肪细胞中4E-BP1磷酸化的影响（随后进行了凝胶移位测定和P-32的掺入）及其与eIF-4E的关系。几条证据表明，有丝分裂原激活的蛋白激酶（MAP激酶）不参与胰岛素的这些作用。尽管EGF活化MAP激酶的程度远高于胰岛素，但胰岛素导致eIF-4E引起的4E-BP1从eIF-4E广泛的磷酸化和解离，而且，与eIF-4E结合时，MAP激酶不会使4E-BP1磷酸化。 。相反，胰岛素将40S核糖体蛋白S6激酶（p70（S6K））激活的程度是EGF的2倍，而激活的时间过程与4E-BP1的磷酸化和解离相似。雷帕霉素是后一种激酶活化的特异性抑制剂，在与胰岛素孵育的细胞中抑制4E-BP1从eIF-4E的解离，但显示出磷酸化形式的4E-BP1仍与eIF-4E结合。结论是，在大鼠附睾脂肪细胞中，胰岛素对4E-BP1的作用涉及多个磷酸化事件。一种磷酸化事件是雷帕霉素不敏感的，仅在结合的4E-BP1上发生，并且不引发解离。第二个事件确实导致解离，并被雷帕霉素阻断，表明涉及p70（S6K）信号传导途径：p70（S6K）本身可能不直接参与，因为该激酶在体外不会磷酸化4E-BP1。

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