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1: J Cell Biol. 2008 Jun 16;181(6):1013-26. Epub 2008 Jun 9.
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p190RhoGAP is the convergence point of adhesion signals from alpha 5 beta 1 integrin and syndecan-4.

Bass MD, Morgan MR, Roach KA, Settleman J, Goryachev AB, Humphries MJ.

Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.

The fibronectin receptors alpha(5)beta(1) integrin and syndecan-4 cocluster in focal adhesions and coordinate cell migration by making individual contributions to the suppression of RhoA activity during matrix engagement. p190Rho-guanosine triphosphatase-activating protein (GAP) is known to inhibit RhoA during the early stages of cell spreading in an Src-dependent manner. This paper dissects the mechanisms of p190RhoGAP regulation and distinguishes the contributions of alpha(5)beta(1) integrin and syndecan-4. Matrix-induced tyrosine phosphorylation of p190RhoGAP is stimulated solely by engagement of alpha(5)beta(1) integrin and is independent of syndecan-4. Parallel engagement of syndecan-4 causes redistribution of the tyrosine-phosphorylated pool of p190RhoGAP between membrane and cytosolic fractions by a mechanism that requires direct activation of protein kinase C alpha by syndecan-4. Activation of both pathways is necessary for the efficient regulation of RhoA and, as a consequence, focal adhesion formation. Accordingly, we identify p190RhoGAP as the convergence point for adhesive signals mediated by alpha(5)beta(1) integrin and syndecan-4. This molecular mechanism explains the cooperation between extracellular matrix receptors during cell adhesion.

Publication Types:
PMID: 18541700 [PubMed - indexed for MEDLINE]

PMCID: PMC2426943 [Available on 12/16/08]