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Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA

Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA ▿ † 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 Duñach 1 , * 1 Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain 2 Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain 3 Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas, Salamanca, Spain ABSTRACT 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA

Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA

Molecular and Cellular Biology , Volume 27 (5): 1745 – Mar 1, 2007

Abstract

Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA ▿ † 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 Duñach 1 , * 1 Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain 2 Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain 3 Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas, Salamanca, Spain ABSTRACT 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.

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References (40)

Publisher
American Society For Microbiology
Copyright
Copyright © 2007 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.01974-06
pmid
17194753
Publisher site
See Article on Publisher Site

Abstract

Specific Phosphorylation of p120-Catenin Regulatory Domain Differently Modulates Its Binding to RhoA ▿ † 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 Duñach 1 , * 1 Unitat de Biofísica, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain 2 Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain 3 Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas, Salamanca, Spain ABSTRACT 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.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Mar 1, 2007

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