...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Transmembrane phosphoprotein Cbp senses cell adhesion signaling mediated by Src family kinase in lipid rafts
【24h】

Transmembrane phosphoprotein Cbp senses cell adhesion signaling mediated by Src family kinase in lipid rafts

机译：跨膜磷蛋白Cbp感知脂质筏中Src家族激酶介导的细胞粘附信号

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

Cbp, a C-terminal Src kinase (Csk)-binding protein, is a transmem-brane phosphoprotein that has been implicated in the regulation of the Src family kinase (SFK) through recruiting Csk, a negative regulator of SFK, to a membrane microdomain of lipid rafts. To examine the contribution of Cbp to cell adhesion signaling mediated by SFK, we investigated the kinase responsible for phosphor-ylating Cbp and the mode of phosphorylation during the cell adhesion process. The results obtained by using mutant mice or cells that lack Csk and/or a member of SFK, Fyn, reveal that Cbp is phosphorylated predominantly by raft-localized Fyn in vivo. Upon cell adhesion onto fibronectin, Cbp becomes transiently phosphorylated (consistent with SFK activation) and recruits Csk to lipid rafts. These events are completed before the full activation of focal adhesion kinase, indicating that the transient activation and down-regulation of SFK in lipid rafts are earlier events in cell adhesion signaling. In Csk-deficient cells, continuous hyperactivation of SFK leads to continuous hyperphosphorylation of Cbp, accompanied by impaired cell spreading and migration. Silencing of Cbp by RNA interference also induced impaired cell spreading. These findings suggest that Cbp could serve as a sensor of SFK activity in early stages of cell adhesion signaling, and that Csk-mediated down-regulation of SFK is essential to allow dynamic cellular events involved in the regulation of cell spreading and migration.
机译：Cbp，一种C端Src激酶（Csk）结合蛋白，是一种跨膜磷酸化蛋白，通过募集SFK的负调节剂Csk到膜微结构域，参与了Src家族激酶（SFK）的调节。脂筏。为了检查Cbp对SFK介导的细胞粘附信号的贡献，我们研究了负责磷酸化Cbp的激酶和细胞粘附过程中的磷酸化模式。通过使用缺少Csk和/或SFK成员Fyn的突变小鼠或细胞获得的结果表明，Cbp主要在体内被筏定位的Fyn磷酸化。一旦细胞粘附到纤连蛋白上，Cbp就会被短暂磷酸化（与SFK激活一致），并将Csk募集到脂质筏中。这些事件在粘着斑激酶完全激活之前完成，表明脂质筏中SFK的瞬时激活和下调是细胞粘附信号传导中的较早事件。在缺乏Csk的细胞中，SFK的持续过度活化会导致Cbp的持续过度磷酸化，并伴随着细胞扩散和迁移受损。 RNA干扰使Cbp沉默也导致细胞扩散受损。这些发现表明，Cbp可以在细胞粘附信号的早期阶段充当SFK活性的传感器，并且Csk介导的SFK下调对于允许参与细胞扩散和迁移调控的动态细胞事件至关重要。

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