FAK phosphorylation at Tyr-925 regulates cross-talk between focal adhesion turnover and cell protrusion.
FAK phosphorylation at Tyr-925 regulates cross-talk between focal adhesion turnover and cell protrusion.
复制标题
DOI：
10.1091/mbc.e10-08-0725
复制
发表时间：
2011-04
影响因子：
3.3
通讯作者：
Rondé P
中科院分区：
文献类型：
--
作者：
Deramaudt TB;Dujardin D;Hamadi A;Noulet F;Kolli K;De Mey J;Takeda K;Rondé P
FAK在细胞迁移的调节中发挥着关键作用。作者表明，FAK在Tyr-925处的磷酸化状态参与FA周转、FA形成和细胞边缘突起增加，以及p130 CAS/Rac 1信号通路的激活。 细胞迁移是一个高度复杂的过程，需要膜突起和粘着斑（FA）的协调形成。粘着斑激酶（FAK）是脂肪酸的主要信号成分，通过酪氨酸残基的磷酸化和去磷酸化参与脂肪酸的分解过程，但这种磷酸化在新生脂肪酸形成和细胞前端附近的周转以及在细胞突起中的作用还不太清楚。在本研究中，我们证明，依赖于Tyr-925残基的磷酸化状态，FAK通过两种特定的机制调节细胞迁移。表达非磷酸化Y 925 F-FAK的FAK−/−小鼠胚胎成纤维细胞（MEFs）显示FAK和非磷酸化桩蛋白之间的相互作用增加，这导致FA稳定，从而降低FA周转和细胞迁移。相反，MEFs表达磷酸化模拟Y 925 E-FAK显示不变的FA解体率，显示增加磷酸化桩蛋白在FA，并表现出增加的新生FA在细胞前缘的形成。此外，Y 925 E-FAK细胞呈现增强的细胞突起以及p130 CAS/Dock 180/Rac 1信号通路的激活。总之，我们的结果表明，FAK在Tyr-925的磷酸化是FAK介导的细胞迁移和细胞突起所必需的。
FAK plays a key role in the regulation of cell migration. The authors show that the phosphorylation status of FAK at Tyr-925 is involved in FA turnover, formation of FAs, and increase in cell edge protrusion, together with activation of the p130CAS/Rac1 signaling pathway. Cell migration is a highly complex process that requires the coordinated formation of membrane protrusion and focal adhesions (FAs). Focal adhesion kinase (FAK), a major signaling component of FAs, is involved in the disassembly process of FAs through phosphorylation and dephosphorylation of its tyrosine residues, but the role of such phosphorylations in nascent FA formation and turnover near the cell front and in cell protrusion is less well understood. In the present study, we demonstrate that, depending on the phosphorylation status of Tyr-925 residue, FAK modulates cell migration via two specific mechanisms. FAK−/− mouse embryonic fibroblasts (MEFs) expressing nonphosphorylatable Y925F-FAK show increased interactions between FAK and unphosphorylated paxillin, which lead to FA stabilization and thus decreased FA turnover and reduced cell migration. Conversely, MEFs expressing phosphomimetic Y925E-FAK display unchanged FA disassembly rates, show increase in phosphorylated paxillin in FAs, and exhibit increased formation of nascent FAs at the cell leading edges. Moreover, Y925E-FAK cells present enhanced cell protrusion together with activation of the p130CAS/Dock180/Rac1 signaling pathway. Together, our results demonstrate that phosphorylation of FAK at Tyr-925 is required for FAK-mediated cell migration and cell protrusion.