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 interactions 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-coupled receptor kinase-interacting protein known as GIT1. Overexpression of GIT1 in fibroblasts or epithelial cells causes a loss of paxillin from FCs and stimulates cell motility. This is due to the direct interaction of a C-terminal 125-residue domain of GIT1 with paxillin, under the regulation of PIX. In its activated state, GIT1 can promote FC disassembly independent of actin-myosin contractile events. Additionally, GIT directly couples to a key component of FCs, focal adhesion kinase (FAK), via a conserved Spa2 homology domain. We propose that GIT1 and FAK cooperate to promote motility both by directly regulating focal complex dynamics and by the activation of Rac.
Pubmed ID: 10938112 RIS Download
Adaptor Proteins, Signal Transducing | Animals | COS Cells | Cell Cycle Proteins | Cell Movement | Chickens | Cytoskeletal Proteins | Cytoskeleton | DNA, Complementary | Epithelial Cells | Fibroblasts | Fungal Proteins | GTPase-Activating Proteins | Glutathione Transferase | Guanine Nucleotide Exchange Factors | HeLa Cells | Humans | Microscopy, Phase-Contrast | Models, Biological | Oncogene Proteins | Paxillin | Phosphoproteins | Plasmids | Precipitin Tests | Protein Binding | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Rho Guanine Nucleotide Exchange Factors | Saccharomyces cerevisiae Proteins | Signal Transduction | Transfection | p21-Activated Kinases | rac GTP-Binding Proteins | src Homology Domains