...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Association of Tyrosine Phosphatase Epsilon with Microtubules Inhibits Phosphatase Activity and Is Regulated by the Epidermal Growth Factor Receptor
【24h】

Association of Tyrosine Phosphatase Epsilon with Microtubules Inhibits Phosphatase Activity and Is Regulated by the Epidermal Growth Factor Receptor

机译：酪氨酸磷酸酶Epsilon与微管的协会抑制磷酸酶活性，并受表皮生长因子受体的调节。

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

摘要

Protein tyrosine phosphatases (PTPs) are key mediators that link physiological cues with reversible changes in protein structure and function; nevertheless, significant details concerning their regulation in vivo remain unknown. We demonstrate that PTPε associates with microtubules in vivo and is inhibited by them in a noncompetitive manner. Microtubule-associated proteins, which interact strongly with microtubules in vivo, significantly increase binding of PTPε to tubulin in vitro and further reduce phosphatase activity. Conversely, disruption of microtubule structures in cells reduces their association with PTPε, alters the subcellular localization of the phosphatase, and increases its specific activity. Activation of the epidermal growth factor receptor (EGFR) increases the PTPε-microtubule association in a manner dependent upon EGFR-induced phosphorylation of PTPε at Y638 and upon microtubule integrity. These events are transient and occur with rapid kinetics similar to EGFR autophosphorylation, suggesting that activation of the EGFR transiently down-regulates PTPε activity near the receptor by promoting the PTPε-microtubule association. Tubulin also inhibits the tyrosine phosphatase PTP1B but not receptor-type PTPμ or the unrelated alkaline phosphatase. The data suggest that reversible association with microtubules is a novel, physiologically regulated mechanism for regulation of tyrosine phosphatase activity in cells.
机译：蛋白质酪氨酸磷酸酶（PTP）是将生理线索与蛋白质结构和功能的可逆变化联系在一起的关键介体。然而，关于它们在体内的调节的重要细节仍然未知。我们证明PTPε与体内的微管相关联，并以非竞争的方式被它们抑制。与微管在体内强烈相互作用的微管相关蛋白，在体外显着增加PTPε与微管蛋白的结合并进一步降低磷酸酶活性。相反，细胞中微管结构的破坏降低了它们与PTPε的结合，改变了磷酸酶的亚细胞定位，并增加了其比活性。表皮生长因子受体（EGFR）的激活以依赖于EGFR诱导的Y638磷酸化PTPε磷酸化以及微管完整性的方式增加了PTPε-微管结合。这些事件是短暂的，并且以类似于EGFR自磷酸化的快速动力学发生，表明EGFR的激活通过促进PTPε-微管缔合而瞬时下调受体附近的PTPε活性。微管蛋白还抑制酪氨酸磷酸酶PTP1B，但不抑制受体型PTPμ或无关的碱性磷酸酶。数据表明，与微管的可逆结合是调节细胞中酪氨酸磷酸酶活性的一种新的，生理上调节的机制。

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