Refeeding and insulin activate the AKT/p70S6 kinase pathway without affecting IRS 1 tyrosine phosphorylation in chicken muscle
Refeeding and insulin activate the AKT/p70S6 kinase pathway without affecting IRS 1 tyrosine phosphorylation in chicken muscle
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DOI：
10.1016/j.domaniend.2006.09.002
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Tesseraud, Sophie
中科院分区：
文献类型：
--
作者：
Duchene, Sophie;Metayer, Sonia;Tesseraud, Sophie
p70 S6激酶（p70 S6 K）是参与蛋白质合成控制的关键酶。我们以前已经表明，这种激酶在鸡肌肉中是胰岛素敏感的，尽管在该组织中胰岛素受体信号传导的早期步骤中存在相对胰岛素抵抗，特别是胰岛素受体底物1（IRS 1）的酪氨酸磷酸化没有变化。本研究的目的是进一步研究鸡肌肉中p70 S6 K信号通路。通过对鸡体内参与蛋白激酶B（PKB，也称AKT）/雷帕霉素靶蛋白（TOR）/p70 S6 K通路的几种激酶的计算机分析，发现这些蛋白质的氨基酸序列与哺乳动物和果蝇中的同源物具有很高的同源性。我们研究了这些激酶在体内或体外的调节。再喂养和胰岛素处理显著（P < 0.05）增加了p70 S6 K上游激酶如AKT和TOR的磷酸化和/或活性。类似地，再喂养和胰岛素增加了关键残基（即T389、T229和T421/S424）上的p70 S6 K的磷酸化以及p70 S6 K下游靶核糖体蛋白S6的磷酸化（3-10倍，P < 0.05）。有趣的是，我们还发现IRS 1在S632/S635上的磷酸化水平增加，这些位点与胰岛素抵抗有关。结论：AKT/TOR/p70 S6 K通路在再喂养和胰岛素注射后被激活，可能负性调节IRS 1酪氨酸磷酸化。这些结果表明，鸡肌肉中的胰岛素信号转导的一些特殊性，并建议在这些功能的p70 S6 K的参与。(c)2006年爱思唯尔公司All rights reserved.
p70 S6 kinase (p70S6K) is a key enzyme involved in the control of protein synthesis. We have previously shown that this kinase is insulin sensitive in chicken muscle despite a relative insulin resistance in the early steps of insulin receptor signaling in this tissue, particularly with no change in tyrosine phosphorylation of the insulin receptor substrate 1(IRS 1). The aim of the present study is to further study the p70S6K pathway in chicken muscle. By analyzing in silico several kinases involved in the protein kinase B (PKB also called AKT)/target of rapamycin (TOR)/p70S6K pathway in the chicken, we showed that the amino acid sequence of the proteins exhibited a very high identity with their homologs in mammalian species and Drosophila. We investigated the regulation of these kinases in vivo or in vitro. Refeeding and insulin treatment significantly (P < 0.05) increased the phosphorylation and/or activity of kinases upstream of p70S6K such as AKT and TOR. Similarly, refeeding and insulin increased the phosphorylation of p70S6K on key residues (i.e. T389, T229 and T421/S424) and the phosphorylation of a p70S6K downstream target, the ribosomal protein S6 (by 3-10-fold, P < 0.05). Interestingly, we also showed an increase in the phosphorylation level of IRS 1 on S632/S635, sites involved in insulin resistance. In conclusion, the AKT/TOR/p70S6K pathway is activated by refeeding and insulin injection, which might negatively regulate IRS 1 tyrosine phosphorylation. These results indicate some particularities of the insulin signaling in chicken muscle and suggest the involvement of p70S6K in these features. (c) 2006 Elsevier Inc. All rights reserved.