• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The Neuron-Specific Rai (ShcC) Adaptor Protein Inhibits Apoptosis by Coupling Ret to the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway
【24h】

The Neuron-Specific Rai (ShcC) Adaptor Protein Inhibits Apoptosis by Coupling Ret to the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway

机译：神经元特异性Rai（ShcC）衔接子蛋白通过将Ret偶联至磷脂酰肌醇3-激酶/ Akt信号通路来抑制细胞凋亡。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Rai is a recently identified member of the family of Shc-like proteins, which are cytoplasmic signal transducers characterized by the unique PTB-CH1-SH2 modular organization. Rai expression is restricted to neuronal cells and regulates in vivo the number of postmitotic sympathetic neurons. We report here that Rai is not a common substrate of receptor tyrosine kinases under physiological conditions and that among the analyzed receptors (Ret, epidermal growth factor receptor, and TrkA) it is activated specifically by Ret. Overexpression of Rai in neuronal cell lines promoted survival by reducing apoptosis both under conditions of limited availability of the Ret ligand glial cell line-derived neurotrophic factor (GDNF) and in the absence of Ret activation. Overexpressed Rai resulted in the potentiation of the Ret-dependent activation of phosphatidylinositol 3-kinase (PI3K) and Akt. Notably, increased Akt phosphorylation and PI3K activity were also found under basal conditions, e.g., in serum-starved neuronal cells. Phosphorylated and hypophosphorylated Rai proteins form a constitutive complex with the p85 subunit of PI3K: upon Ret triggering, the Rai-PI3K complex is recruited to the tyrosine-phosphorylated Ret receptor through the binding of the Rai PTB domain to tyrosine 1062 of Ret. In neurons treated with low concentrations of GDNF, the prosurvival effect of Rai depends on Rai phosphorylation and Ret activation. In the absence of Ret activation, the prosurvival effect of Rai is, instead, phosphorylation independent. Finally, we showed that overexpression of Rai, at variance with Shc, had no effects on the early peak of mitogen-activated protein kinase (MAPK) activation, whereas it increased its activation at later time points. Phosphorylated Rai, however, was not found in complexes with Grb2. We propose that Rai potentiates the MAPK and PI3K signaling pathways and regulates Ret-dependent and -independent survival signals.
机译：Rai是Shc-like蛋白家族中最近被鉴定的成员，它们是具有独特PTB-CH1-SH2模块化组织特征的细胞质信号转导子。 Rai表达仅限于神经元细胞，并在体内调节有丝分裂后交感神经元的数量。我们在这里报告说，在生理条件下，Rai不是受体酪氨酸激酶的常见底物，在分析的受体（Ret，表皮生长因子受体和TrkA）中，Rai会被Ret特异性激活。在有限的Ret配体神经胶质细胞系衍生的神经营养因子（GDNF）的可用性和没有Ret激活的条件下，Rai在神经元细胞系中的过表达可通过减少凋亡来促进存活。过表达的Rai导致磷脂酰肌醇3-激酶（PI3K）和Akt依赖于Ret的激活作用增强。值得注意的是，在基础条件下，例如在血清饥饿的神经元细胞中也发现增加的Akt磷酸化和PI3K活性。磷酸化和次磷酸化的Rai蛋白与PI3K的p85亚基形成组成型复合物：Ret触发后，Rai-PI3K复合物通过Rai PTB结构域与Ret的酪氨酸1062的结合而被募集到酪氨酸磷酸化的Ret受体。在用低浓度GDNF治疗的神经元中，Rai的生存作用取决于Rai磷酸化和Ret激活。在没有Ret激活的情况下，Rai的生存作用是独立于磷酸化的。最后，我们显示Rai的过表达与Shc有所不同，对丝裂原激活的蛋白激酶（MAPK）激活的早期峰值没有影响，而在以后的时间点增加了其激活。然而，在与Grb2的复合物中未发现磷酸化的Rai。我们建议Rai增强MAPK和PI3K信号通路并调节Ret依赖性和非依赖性生存信号。

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