Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.
Mol Cell Biol. 2010 Jul;30(13):3233-48. doi: 10.1128/MCB.01178-09. Epub 2010 May 3.
Cell migration is critical for normal development and for pathological processes including cancer cell metastasis. Dynamic remodeling of focal adhesions and the actin cytoskeleton are crucial determinants of cell motility. The Rho family and the mitogen-activated protein kinase (MAPK) module consisting of MEK-extracellular signal-regulated kinase (ERK) are important regulators of these processes, but mechanisms for the integration of these signals during spreading and motility are incompletely understood. Here we show that ERK activity is required for fibronectin-stimulated Rho-GTP loading, Rho-kinase function, and the maturation of focal adhesions in spreading cells. We identify p190A RhoGAP as a major target for ERK signaling in adhesion assembly and identify roles for ERK phosphorylation of the C terminus in p190A localization and activity. These observations reveal a novel role for ERK signaling in adhesion assembly in addition to its established role in adhesion disassembly.
细胞迁移对于正常发育以及包括癌细胞转移在内的病理过程至关重要。粘着斑和肌动蛋白细胞骨架的动态重塑是细胞运动的关键决定因素。Rho 家族和由 MEK-细胞外信号调节激酶 (ERK) 组成的丝裂原激活蛋白激酶 (MAPK) 模块是这些过程的重要调节剂，但在扩展和运动过程中整合这些信号的机制尚不完全清楚。在这里，我们表明 ERK 活性对于纤维连接蛋白刺激的 Rho-GTP 加载、Rho-激酶功能以及扩展细胞中粘着斑的成熟是必需的。我们确定 p190A RhoGAP 是粘着组装中 ERK 信号的主要靶点，并确定 ERK 对 C 末端的磷酸化在 p190A 定位和活性中的作用。这些观察结果揭示了 ERK 信号在粘着组装中的新作用，除了其在粘着解组装中的既定作用之外。
