1. Academic Validation
  2. Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly

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

  • Mol Cell Biol. 2000 Sep;20(17):6354-63. doi: 10.1128/MCB.20.17.6354-6363.2000.
Z S Zhao 1 E Manser T H Loo L Lim
Affiliations

Affiliation

  • 1 Glaxo-IMCB Group, Institute of Molecular and Cell Biology, Singapore 117609, Singapore.
Abstract

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.

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