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Molecular and Cellular Biology, March 2007, p. 1745-1757, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01974-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA{triangledown} ,{dagger}

Julio Castaño,1 Guiomar Solanas,1 David Casagolda,1 Imma Raurell,1 Patricia Villagrasa,1,2 Xosé R. Bustelo,3 Antonio García de Herreros,2* and Mireia Duñach1*

Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain,1 Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain,2 Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas, Salamanca, Spain3

Received 20 October 2006/ Returned for modification 25 October 2006/ Accepted 14 December 2006

p120-catenin is an adherens junction-associated protein that controls E-cadherin function and stability. p120-catenin also binds intracellular proteins, such as the small GTPase RhoA. In this paper, we identify the p120-catenin N-terminal regulatory domain as the docking site for RhoA. Moreover, we demonstrate that the binding of RhoA to p120-catenin is tightly controlled by the Src family-dependent phosphorylation of p120-catenin on tyrosine residues. The phosphorylation induced by Src and Fyn tyrosine kinases on p120-catenin induces opposite effects on RhoA binding. Fyn, by phosphorylating a residue located in the regulatory domain of p120-catenin (Tyr112), inhibits the interaction of this protein with RhoA. By contrast, the phosphorylation of Tyr217 and Tyr228 by Src promotes a better affinity of p120-catenin towards RhoA. In agreement with these biochemical data, results obtained in cell lines support the important role of these phosphorylation sites in the regulation of RhoA activity by p120-catenin. Taken together, these observations uncover a new regulatory mechanism acting on p120-catenin that contributes to the fine-tuned regulation of the RhoA pathways during specific signaling events.

* Corresponding author. Mailing address for Mireia Duñach: Unitat de Biofísica, Departament Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain. Phone: 34-93-581-1870. Fax: 34-93-581-1907. E-mail: mireia.dunach{at}uab.es. Mailing address for Antonio García de Herreros: Institut Municipal d'Investigació Mèdica, c/ Dr. Aiguader 80, E-08003 Barcelona, Spain. Phone: 34-93-221-1009. Fax: 34-93-221-3237. E-mail: agarcia{at}imim.es.

{triangledown} Published ahead of print on 28 December 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2007, p. 1745-1757, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01974-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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