...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of cellular biochemistry. >Role of mTOR in the degradation of IRS-1: Regulation of PP2A activity.
【24h】

Role of mTOR in the degradation of IRS-1: Regulation of PP2A activity.

机译：mTOR在IRS-1降解中的作用：调节PP2A活性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We have investigated the role of PI 3-kinase and mTOR in the degradation of IRS-1 induced by insulin. Inhibition of mTOR with rapamycin resulted in approximately 50% inhibition of the insulin-induced degradation of IRS-1. In contrast, inhibition of PI-3 kinase, an upstream activator of mTOR, leads to a complete block of the insulin-induced degradation. Inhibition of either PI-3 kinase or mTOR prevented the mobility shift in IRS-1 in response to insulin, a shift that is caused by Ser/Thr phosphorylation. These results indicate that insulin stimulates PI 3-kinase-mediated degradation of IRS-1 via both mTOR-dependent and -independent pathways. Platelet-derived growth factor (PDGF) stimulation leads to a lower level of degradation, but significant phosphorylation of IRS-1. Both the degradation and phosphorylation of IRS-1 in response to PDGF are completely inhibited by rapamycin, suggesting that PDGF stimulates IRS-1 degradation principally via the mTOR-dependent pathway. Inhibition of the serine/threonine phosphatase PP2A with okadaic acid also induced the phosphorylation and degradation of IRS-1. IRS-1 phosphorylation and degradation in response to okadaic acid were not inhibited by rapamycin, suggesting that the action of mTOR in the degradation of IRS-1 results from inhibition of PP2A. Consistent with this, treatment of cells with rapamycin stimulated PP2A activity. While the role of mTOR in the phosphorylation of IRS-1 appears to proceed primarily through the regulation of PP2A, we also provide evidence that the regulation of p70S6 kinase phosphorylation requires the direct activity of mTOR.
机译：我们已经研究了PI 3-激酶和mTOR在胰岛素诱导的IRS-1降解中的作用。雷帕霉素对mTOR的抑制作用导致胰岛素诱导的IRS-1降解的抑制作用约为50％。相反，抑制PI-3激酶（mTOR的上游激活剂）可完全阻断胰岛素诱导的降解。 PI-3激酶或mTOR的抑制均阻止了IRS-1响应胰岛素而发生的迁移率变化，这是由Ser / Thr磷酸化引起的。这些结果表明，胰岛素通过mTOR依赖性和非依赖性途径刺激PI 3激酶介导的IRS-1降解。血小板衍生的生长因子（PDGF）刺激导致降解水平降低，但IRS-1磷酸化明显。雷帕霉素完全抑制了响应PDGF的IRS-1的降解和磷酸化，这表明PDGF主要通过mTOR依赖性途径刺激IRS-1降解。冈田酸对丝氨酸/苏氨酸磷酸酶PP2A的抑制作用还诱导了IRS-1的磷酸化和降解。雷帕霉素并未抑制IRS-1的磷酸化和对冈田酸的降解，这表明mTOR在IRS-1降解中的作用是由PP2A的抑制引起的。与此相一致，用雷帕霉素处理细胞会刺激PP2A活性。尽管mTOR在IRS-1磷酸化中的作用似乎主要是通过PP2A的调控来进行，但我们也提供了p70S6激酶磷酸化的调控需要mTOR直接活性的证据。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号