• 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 Cytoplasmic Tyrosines of Integrin Subunit β1 Are Involved in Focal Adhesion Kinase Activation
【24h】

The Cytoplasmic Tyrosines of Integrin Subunit β1 Are Involved in Focal Adhesion Kinase Activation

机译：整合素亚基β1的胞质酪氨酸参与局灶性粘附激酶激活。

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

摘要

We have previously shown that mutation of the two tyrosines in the cytoplasmic domain of integrin subunit β1 (Y783 and Y795) to phenylalanines markedly reduces the capability of β1A integrins to mediate directed cell migration. In this study, β1-dependent cell spreading was found to be delayed in GD25 cells expressing β1AY783/795F compared to that in wild-type GD25-β1A. Focal adhesion kinase (FAK) tyrosine phosphorylation and activation were severely impaired in response to β1-dependent adhesion in GD25-β1AY783/795F cells compared to that in wild-type GD25-β1A or mutants in which only a single tyrosine was altered (β1AY783F or β1AY795F). Phosphorylation site-specific antibodies selective for FAK phosphotyrosine 397 indicated that the defect in FAK phosphorylation via β1AY783/795F lies at the level of the initial autophosphorylation step. Indeed, β1A-dependent tyrosine phosphorylation of tensin and paxillin was lost in the β1AY783/795F cells, consistent with the impairment in FAK activation. In contrast, p130CAS overall tyrosine phosphorylation was unaffected by the β1 mutations. Despite the defect in β1-mediated FAK activation, FAK was still localized to focal adhesions. Taken together, the phenotype of the GD25-β1AY783/795F cells resembles, but is distinct from, the phenotype observed in FAK-null cells. These observations argue that tyrosines 783 and 795 within the cytoplasmic tail of integrin subunit β1A are critical mediators of FAK activation and cell spreading in GD25 cells.
机译：先前我们已经表明，整联蛋白亚基β1的胞质域中的两个酪氨酸突变（Y783和Y795）变为苯丙氨酸显着降低了β1A整联蛋白介导定向细胞迁移的能力。在这项研究中，与野生型GD25-β1A相比，发现表达β1A Y783 / 795F 的GD25细胞延迟了β1依赖性细胞的扩散。与野生型GD25-β1A或仅突变型GD25-β1A的突变体相比，GD25-β1A Y783 / 795F 细胞中与β1依赖的粘附反应严重损害了黏着斑激酶（FAK）酪氨酸的磷酸化和激活。改变了一个酪氨酸（β1A Y783F 或β1A Y795F ）。对FAK磷酸酪氨酸397有选择性的磷酸化位点特异性抗体表明，通过β1A Y783 / 795F 进行的FAK磷酸化缺陷位于初始自磷酸化步骤的水平。确实，β1A Y783 / 795F 细胞中，β1A依赖的酪氨酸和paxillin酪氨酸磷酸化丢失，这与FAK激活受损有关。相反，p130 CAS 酪氨酸的整体磷酸化不受β1突变的影响。尽管β1介导的FAK激活存在缺陷，但FAK仍局限于粘着斑。两者合计，GD25-β1A Y783 / 795F 细胞的表型类似于但不同于FAK空细胞中观察到的表型。这些观察结果表明，整联蛋白亚基β1A胞质尾中的酪氨酸783和795是FAK活化和GD25细胞中细胞扩散的关键介体。

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