...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular cell >The Signaling Adaptor Gab1 Regulates Cell Polarity by Acting as a PAR Protein Scaffold
【24h】

The Signaling Adaptor Gab1 Regulates Cell Polarity by Acting as a PAR Protein Scaffold

机译：信号适配器Gab1通过充当PAR蛋白支架来调节细胞极性

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

Cell polarity plays a key role in development and is disrupted in tumors, yet the molecules and mechanisms that regulate polarity remain poorly defined. We found that the scaffolding adaptor GAB1 interacts with two polarity proteins, PAR1 and PAR3. GAB1 binds PAR1 and enhances its kinase activity. GAB1 brings PAR1 and PAR3 into a transient complex, stimulating PAR3 phosphorylation by PAR1. GAB1 and PAR6 bind the PAR3 PDZ1 domain and thereby compete for PAR3 binding. Consequently, GAB1 depletion causes PAR3 hypophosphorylation and increases PAR3/PAR6 complex formation, resulting in accelerated and enhanced tight junction formation, increased transepithelial resistance, and lateral domain shortening. Conversely, GAB1 overexpression, in a PAR1/PAR3-dependent manner, disrupts epithelial apical-basal polarity, promotes multilumen cyst formation, and enhances growth factor-induced epithelial cell scattering. Our results identify GAB1 as a negative regulator of epithelial cell polarity that functions as a scaffold for modulating PAR protein complexes on the lateral membrane.
机译：细胞极性在发育中起关键作用，并在肿瘤中被破坏，但是调节极性的分子和机制仍然定义不清。我们发现脚手架适配器GAB1与两个极性蛋白PAR1和PAR3相互作用。 GAB1结合PAR1并增强其激酶活性。 GAB1将PAR1和PAR3引入一个瞬时复合物中，从而刺激PAR1磷酸化PAR3。 GAB1和PAR6结合PAR3 PDZ1域，从而竞争PAR3结合。因此，GAB1耗尽会导致PAR3磷酸化不足并增加PAR3 / PAR6复合物的形成，从而导致紧密连接形成的加速和增强，跨上皮电阻的增加和侧向结构域的缩短。相反，GAB1过表达以PAR1 / PAR3依赖性方式破坏上皮顶基极极性，促进多腔囊肿形成，并增强生长因子诱导的上皮细胞散射。我们的研究结果确定GAB1为上皮细胞极性的负调节剂，可作为支架调节侧膜上的PAR蛋白复合物。

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