Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover

Focal adhesion kinase (FAK) is activated and localized at focal adhesions u pon cell adhesion to extracellular matrices. Cells lacking FAK show increas ed focal adhesion number and decreased cell migration, functions that are r egulated by the small GTPase Rho. We now report that fibroblasts from FAK-/ - mice failed to transiently inhibit Rho activity when plated on fibronecti n. Re-expression of FAK restored normal Rho regulation. Turnover of focal a dhesions 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 i nhibition of focal adhesion turnover can account for deficiencies in cell m igration and embryonic lethality of the FAK knockout.