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.
Mesh Terms:
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, Saccharomyces cerevisiae Proteins, Signal Transduction, Transfection, p21-Activated Kinases, rac GTP-Binding Proteins, src Homology Domains
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, Saccharomyces cerevisiae Proteins, Signal Transduction, Transfection, p21-Activated Kinases, rac GTP-Binding Proteins, src Homology Domains
Mol. Cell. Biol.
Date: Sep. 01, 2000
PubMed ID: 10938112
View in: Pubmed Google Scholar
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