• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Mitochondrial AKAP121 Binds and Targets Protein Tyrosine Phosphatase D1, a Novel Positive Regulator of src Signaling
【24h】

Mitochondrial AKAP121 Binds and Targets Protein Tyrosine Phosphatase D1, a Novel Positive Regulator of src Signaling

机译：线粒体AKAP121结合并靶向蛋白酪氨酸磷酸酶D1，一种新型的src信号正调控剂

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

摘要

A-kinase anchor protein 121 (AKAP121) and its spliced isoform AKAP84 anchor protein kinase A (PKA) to the outer membrane of mitochondria, focusing and enhancing cyclic AMP signal transduction to the organelle. We find that AKAP121/84 also binds PTPD1, a src-associated protein tyrosine phosphatase. A signaling complex containing AKAP121, PKA, PTPD1, and src is assembled in vivo. PTPD1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (EGF) signaling. EGF receptor phosphorylation and downstream activation of ERK 1/2 and Elk1-dependent gene transcription are enhanced by PTPD1. Expression of a PTPD1 mutant lacking catalytic activity inhibits src and downregulates ERK 1/2 but does not affect the activity of c-Jun N-terminal kinase 1/2 and p38α mitogen-activated protein kinase. AKAP121 binds to and redistributes PTPD1 from the cytoplasm to mitochondria and inhibits EGF signaling. Our findings indicate that PTPD1 is a novel positive regulator of src signaling and a key component of the EGF transduction pathway. By binding and/or targeting the phosphatase on mitochondria, AKAP121 modulates the amplitude and persistence of src-dependent EGF transduction pathway. This represents the first example of physical and functional interaction between AKAPs and a protein tyrosine phosphatase.
机译：A激酶锚定蛋白121（AKAP121）及其剪接的同工型AKAP84锚定蛋白激酶A（PKA）连接到线粒体的外膜，聚焦并增强环AMP信号转导至细胞器。我们发现AKAP121 / 84还结合PTPD1，一种与src相关的蛋白酪氨酸磷酸酶。在体内组装包含AKAP121，PKA，PTPD1和src的信号复合物。 PTPD1激活src酪氨酸激酶并增加表皮生长因子（EGF）信号传导的强度和持续时间。 PTPD1增强EGF受体的磷酸化和ERK 1/2和Elk1依赖性基因转录的下游激活。缺乏催化活性的PTPD1突变体的表达抑制src并下调ERK 1/2，但不影响c-Jun N端激酶1/2和p38α丝裂原活化蛋白激酶的活性。 AKAP121与PTPD1结合并从细胞质重新分布到线粒体，并抑制EGF信号传导。我们的发现表明PTPD1是src信号的新型正调节剂，是EGF转导途径的关键组成部分。通过结合和/或靶向线粒体上的磷酸酶，AKAP121调节src依赖性EGF转导途径的幅度和持续性。这代表了AKAP与蛋白酪氨酸磷酸酶之间物理和功能相互作用的第一个例子。

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