TY - JOUR
T1 - Specific phosphorylation of p120-catenin regulatory domain differently modulates its binding to RhoA
AU - Castaño, Julio
AU - Solanas, Guiomar
AU - Casagolda, David
AU - Raurell, Imma
AU - Villagrasa, Patricia
AU - Bustelo, Xosé R.
AU - Garcia de Herreros, Antonio
AU - Duñach, Mireia
PY - 2007/3/1
Y1 - 2007/3/1
N2 - 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 elects 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
AB - 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 elects 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. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
U2 - https://doi.org/10.1128/MCB.01974-06
DO - https://doi.org/10.1128/MCB.01974-06
M3 - Article
VL - 27
SP - 1745
EP - 1757
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
ER -