G[alpha]12 binds to the N-terminal regulatory domain of p120ctn, and downregulates p120ctn tyrosine phosphorylation induced by Src family kinases via a RhoA independent mechanism

• Published in: Experimental cell research Vol. 317; no. 3; p. 293
• Main Authors: Ardawatia, Vandana V, Masià-Balagué, Miriam, Krakstad, Beate F, Johansson, Bente B, Kreitzburg, Kelly M, Spriet, Endy, Lewis, Aurélia E, Meigs, Thomas E, Aragay, Anna M
• Format: Journal Article
• Language: English
• Published: New York Elsevier BV 01.02.2011
• Subjects: Amino acids; Binding sites; Cell adhesion & migration; Phosphorylation; Signal transduction
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.10.017

p120 catenin (p120ctn ) regulates cadherin stability, and thus facilitates strong cell-cell adhesion. Previously, we demonstrated that G[alpha]12 interacts with p120ctn . In the present study, we have delineated a region of p120ctn that binds to G[alpha]12 . We report that the N-terminal region of p120ctn (amino acids 1-346) is necessary and sufficient for the interaction. While the coiled-coiled domain and a charged region, comprising a.a 102-120, were found to be dispensable, amino acids 121-323 were required for p120ctn binding to G[alpha]12 . This region harbors the phosphorylation domain of p120ctn and has been postulated as important for RhoA regulation. Downregulation of Src family kinase-induced tyrosine phosphorylation of p120ctn was observed in the presence of activated G[alpha]12 . This down-regulation was triggered by three different G[alpha]12 mutants uncoupled from RhoA signalling. Furthermore, a dominant active form of RhoA did not reduce Src-induced phosphoryaltion of p120ctn . In summary, our results suggest that G[alpha]12 binds to p120ctn and modulates its phosphorylation status through a Rho-independent mechanism. G[alpha]12 emerges as an important regulator of p120ctn function, and possibly of cadherin-mediated adhesion and/or cell motility. [PUBLICATION ABSTRACT]