• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell motility and the cytoskeleton >Requirement of reversible caldesmon phosphorylation at P21-activated kinase-responsive sites for lamellipodia extensions during cell migration.
【24h】

Requirement of reversible caldesmon phosphorylation at P21-activated kinase-responsive sites for lamellipodia extensions during cell migration.

机译：对P21激活的激酶反应位点在细胞迁移过程中发生lamellipodia延伸的可逆Caldesmon磷酸化的要求。

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

Caldesmon is believed to be one of the key regulators for actin dynamics and thereby cell polarity, membrane extension, and cell motility. We have shown previously that stress fiber formation and cell movement are severely impaired in the cells expressing human fibroblast caldesmon fragment defective in Ca2+/CaM binding sites. Both Ser458 and Ser489, adjacent to the Ca2+/CaM-binding sites, are phosphorylated by p21-activated kinase (PAK) in vitro. Here we report that Ser458 is phosphorylated in response to cell movement. We substituted Ser458 and Ser489 on C-terminal caldesmon (CaD39) with alanine or glutamic acid to mimic under-phosphorylated (CaD39-PAKA) or constitutively phosphorylated (CaD39-PAKE) caldesmon. In vitro, CaD39-PAKE, but not CaD39-PAKA, fails to inhibit myosin ATPase activity and exhibits reduced binding to Ca2+/CaM. When stably expressed in Chinese Hamster Ovary cells, both CaD39-PAKA and CaD39-PAKE incorporate into stress fibers and localize to the leading edge of the migrating cell.Expression of CaD39-PAKE, but not CaD39-PAKA, fails to protect stress fibers from cytochalasin depolymerization. However, both mutations inhibit cell polarization and lead to defects in membrane extension and cell migration. We conclude that phosphorylation of caldesmon by PAK is a dynamic process required to regulate actin dynamics and membrane protrusions in wound-induced cell migration.
机译：人们认为Caldesmon是肌动蛋白动力学从而调节细胞极性，膜延伸和细胞运动性的关键调节剂之一。先前我们已经表明，在表达人成纤维细胞caldesmon片段的Ca2 + / CaM结合位点有缺陷的细胞中，应力纤维的形成和细胞运动受到严重损害。在体外，与Ca2 + / CaM结合位点相邻的Ser458和Ser489都被p21活化激酶（PAK）磷酸化。在这里我们报告说Ser458被磷酸化响应细胞运动。我们用丙氨酸或谷氨酸取代C末端caldesmon（CaD39）上的Ser458和Ser489，以模拟磷酸化不足（CaD39-PAKA）或组成型磷酸化（CaD39-PAKE）的caldesmon。在体外，CaD39-PAKE而不是CaD39-PAKA不能抑制肌球蛋白ATPase活性，并且与Ca2 + / CaM的结合减少。当在中国仓鼠卵巢细胞中稳定表达时，CaD39-PAKA和CaD39-PAKE均掺入应力纤维并定位于迁移细胞的前缘.CaD39-PAKE的表达而非CaD39-PAKA的表达无法保护应力纤维免受细胞松弛素解聚。但是，这两种突变均会抑制细胞极化，并导致膜延伸和细胞迁移方面的缺陷。我们得出的结论是，PAK激活了卡尔德斯蒙的磷酸化是调节肌动蛋白动力学和伤口诱导的细胞迁移中的膜突出所需的动态过程。

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