Ren X D, Kiosses W B, Sieg D J, Otey C A, Schlaepfer D D, Schwartz M A
Departments of Vascular Biology and Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Cell Sci. 2000 Oct;113 ( Pt 20):3673-8. doi: 10.1242/jcs.113.20.3673.
Focal adhesion kinase (FAK) is activated and localized at focal adhesions upon cell adhesion to extracellular matrices. Cells lacking FAK show increased focal adhesion number and decreased cell migration, functions that are regulated by the small GTPase Rho. We now report that fibroblasts from FAK-/- mice failed to transiently inhibit Rho activity when plated on fibronectin. Re-expression of FAK restored normal Rho regulation. Turnover of focal adhesions correlated inversely with Rho activity. The presence or absence of FAK was mimicked by inhibiting or activating Rho, respectively. These data suggest that loss of FAK resulting in constitutive activation of Rho and inhibition of focal adhesion turnover can account for deficiencies in cell migration and embryonic lethality of the FAK knockout.
粘着斑激酶（FAK）在细胞粘附于细胞外基质时被激活并定位于粘着斑。缺乏FAK的细胞显示粘着斑数量增加且细胞迁移减少，这些功能受小GTP酶Rho调节。我们现在报告，来自FAK基因敲除小鼠的成纤维细胞在铺于纤连蛋白上时未能短暂抑制Rho活性。FAK的重新表达恢复了正常的Rho调节。粘着斑的周转与Rho活性呈负相关。分别通过抑制或激活Rho来模拟FAK的存在或缺失。这些数据表明，FAK的缺失导致Rho的组成性激活和粘着斑周转的抑制，这可以解释FAK基因敲除小鼠在细胞迁移和胚胎致死方面的缺陷。
