p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho.

Wildenberg GA, Dohn MR, Carnahan RH, Davis MA, Lobdell NA, Settleman J, Reynolds AB
Cell. 2006 127 (5): 1027-39

PMID: 17129786 · DOI:10.1016/j.cell.2006.09.046

Integration of receptor tyrosine kinase, integrin, and cadherin activities is crucial for normal cell growth, motility, and adhesion. Here, we describe roles for p120-catenin (p120) and p190RhoGAP that coordinate crosstalk between these systems and regulate cadherin function. Surprisingly, PDGFR-induced actin remodeling in NIH3T3 cells is blocked in the absence of p120, and the cells are partially transformed via constitutive activation of Rho. We have traced the mechanism to unexpected codependent roles for p120 and p190RhoGAP in regulating Rac-dependent antagonism of Rho. Receptor-induced Rac activity causes translocation of p190RhoGAP to adherens junctions (AJs), where it couples to the cadherin complex via interaction with p120. AJ formation is dependent on this p120-p190RhoGAP interaction and fails altogether if either of these proteins are compromised. We propose that Rac activation links diverse signaling systems to AJ assembly by controlling transient p190RhoGAP interactions with p120 and localized inhibition of Rho.

MeSH Terms (24)

Actins Adherens Junctions Animals Catenins Cell Adhesion Cell Adhesion Molecules Cell Line, Transformed Cell Proliferation Cell Surface Extensions Culture Media, Serum-Free DNA-Binding Proteins Fibroblasts Fibronectins GTPase-Activating Proteins Integrins Mice Models, Biological NIH 3T3 Cells Phosphoproteins rac GTP-Binding Proteins Receptors, Platelet-Derived Growth Factor Repressor Proteins rho GTP-Binding Proteins Stress Fibers

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