Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly

The p21-activated kinase PAK is targeted to focal complexes (FCs) through i nteractions with the SH3 domains of the PAK-interacting exchange factor PIX and Nck PIX is a Rac GTP exchange factor that also binds the G-protein cou pled receptor kinase-interacting protein known as GIT1, Overexpression of G IT1 in fibroblasts or epithelial cells causes a loss of paxillin from FCs a nd stimulates cell motility. This is due to the direct interaction of a C-t erminal 125-residue domain of GIT1 with paxillin, under the regulation of P M. In its activated state, GIT1 can promote FC disassembly independent of a ctin-myosin contractile events. Additionally, GIT directly couples to a key component of FCs, focal adhesion kinase (FAK), via a conserved Spa2 homolo gy domain. We propose that GIT1 and FAK cooperate to promote motility both by directly regulating focal complex dynamics and by the activation of Rac.