p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho.
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.
Wildenberg
Gregg A
GA
Department of Cancer Biology, 438 Preston Building, Vanderbilt University, Nashville, TN 37232, USA.
Dohn
Michael R
MR
Carnahan
Robert H
RH
Davis
Michael A
MA
Lobdell
Nichole A
NA
Settleman
Jeffrey
J
Reynolds
Albert B
AB
D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D051177:Catenins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D022081:Cell Surface Extensions / Q000378:metabolism; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D005353:Fibronectins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000095002:Delta Catenin
D000199:Actins; C513041:Arhgap35 protein, mouse; D051177:Catenins; D015815:Cell Adhesion Molecules; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D005353:Fibronectins; D020690:GTPase-Activating Proteins; D016023:Integrins; D010750:Phosphoproteins; D012097:Repressor Proteins; D017479:Receptors, Platelet-Derived Growth Factor; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse