Regulation of protein synthesis by insulin
Regulation of protein synthesis by insulin
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DOI：
10.1042/bst0340213
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发表时间：
2006-04-01
影响因子：
3.9
通讯作者：
Proud, CG
中科院分区：
文献类型：
--
作者：
Proud, CG
胰岛素通过激活翻译机制的组分，包括E11（真核起始因子）和eEF（真核延伸因子），快速激活蛋白质合成。从长远来看，胰岛素还增加了核糖体的细胞含量，以增强蛋白质合成的能力。胰岛素对蛋白质合成的快速激活主要通过磷酸肌醇3-激酶介导。这涉及PKB（蛋白激酶B）的激活。在一种情况下，RIB作用于磷酸化和磷酸化糖原合成酶激酶3，其继而磷酸化和抑制ORB。胰岛素促进eIF 2B的去磷酸化和活化。由于eIF 2 B是所有细胞质翻译起始事件所需的因子eIF 2的再循环所必需的，因此这将有助于蛋白质合成的整体激活。PKB还磷酸化TSC 1（结节性硬化症复合物1）-TSC 2复合物以减轻其对mTOR（雷帕霉素的哺乳动物靶标）的抑制作用。雷帕霉素对mTOR的抑制显著损害胰岛素活化蛋白的合成。mTOR控制翻译起始和延伸。帽结合因子eIF 4 E可以通过4 E-BP 1（eIF 4 E结合蛋白1）螯合在无活性复合物中。4 E-BP 1的胰岛素释放磷酸化及其从eIF 4 E的释放，允许eIF 4 E形成起始因子复合物。胰岛素诱导eEF 2的去磷酸化和活化以加速延伸。这两种作用都被雷帕霉素阻断。胰岛素通过增加eEF 2激酶在几个mTOR调节位点的磷酸化而使其失活。胰岛素还通过促进核糖体蛋白的mRNA募集到多核糖体中来刺激核糖体蛋白的合成。这被雷帕霉素抑制。几个关键问题仍然存在，例如，mTOR控制4 E-BP 1和eEF 2激酶的机制以及核糖体蛋白翻译的控制。
insulin rapidly activates protein synthesis by activating components of the translational machinery including ell's (eukaryotic initiation factors) and eEFs (eukaryotic elongation factors). in the long term, insulin also increases the cellular content of ribosomes to augment the capacity for protein synthesis. The rapid activation of protein synthesis by insulin is mediated primarily through phosphoinositide 3-kinase. This involves the activation of PKB (protein kinase B). In one case, RIB acts to phosphorylate and inactivate glycogen synthase kinase 3, which in turn phosphorylates and inhibits ORB. Insulin elicits the dephosphorylation and activation of eIF2B. Since eIF2B is required for recycling of eIF2, a factor required for all cytoplasmic translation initiation events, this will contribute to overall activation of protein synthesis. PKB also phosphorylates the TSC1 (tuberous sclerosis complex l)-TSC2 complex to relieve its inhibitory action on the mTOR (mammalian target of rapamycin). inhibition of mTOR by rapamycin markedly impairs insulin-activated protein synthesis. mTOR controls translation initiation and elongation. The cap-binding factor eIF4E can be sequestered in inactive complexes by 4E-BP1 (eIF4E-binding protein 1). insulin elicits phosphorylation of 4E-BP1 and its release from eIF4E, allowing eIF4E to form initiation factor complexes. insulin induces dephosphorylation and activation of eEF2 to accelerate elongation. Both effects are blocked by rapamycin. insulin inactivates eEF2 kinase by increasing its phosphorylation at several mTOR-regulated sites. insulin also stimulates synthesis of ribosomal proteins by promoting recruitment of their mRNAs into polyribosomes. This is inhibited by rapamycin. Several key questions remain about, for example, the mechanisms by which mTOR controls 4E-BP1 and eEF2 kinase and the control of ribosomal protein translation.