Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics
Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics
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DOI：
10.1242/jcs.071555
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发表时间：
2010-10-01
影响因子：
4
通讯作者：
Chang, Zee-Fen
中科院分区：
文献类型：
--
作者：
Lee, Hsiao-Hui;Tien, Sui-Chih;Chang, Zee-Fen
当细胞迁移时，rhoa - rock介导的收缩信号在前缘被抑制，从而允许动态粘附以突出。然而，一些研究已经报道RhoA在血清刺激时确实在迁移细胞的前沿活跃。在这里，我们提供的证据表明，外周局灶接触中Y722位点的ROCKII磷酸化调控对于控制在血清刺激迁移过程中与RhoA激活分离的局灶粘附（FA）复合体的周转至关重要。然而，当血小板衍生生长因子（PDGF）处理的细胞中RhoA下调时，这种磷酸化控制对于迁移是必不可少的。我们进一步证明ROCKII在FAs中被Src磷酸化，这一磷酸化事件降低了ROCKII的RhoA结合活性。在溶血磷脂酸（LPA）刺激期间，缺乏这种调节控制导致肌球蛋白介导的持续收缩和FA延长。总之，我们的数据表明，当RhoA活跃时，src依赖的ROCKII磷酸化提供了调节FAs动力学所需的收缩性的方法。
When a cell migrates, the RhoA-ROCK-mediated contractile signal is suppressed in the leading edge to allow dynamic adhesions for protrusion. However, several studies have reported that RhoA is indeed active in the leading edge of a migrating cell during serum stimulation. Here, we present evidence that regulation of ROCKII phosphorylation at the Y722 site in peripheral focal contacts is crucial for controlling the turnover of the focal adhesion (FA) complex uncoupled from RhoA activation during serum-stimulated migration. However, this phosphorylation control is dispensable for migration when RhoA is downregulated in cells treated with platelet-derived growth factor (PDGF). We further present evidence that ROCKII is phosphorylated by Src in FAs and this phosphorylation event decreases RhoA binding activity of ROCKII. Lack of this regulatory control leads to sustained myosin-mediated contractility and FA elongation during lysophosphatidic acid (LPA) stimulation. Altogether, our data suggest that Src-dependent ROCKII phosphorylation provides a means of tuning contractility required for FAs dynamics when RhoA is active.