Specific phosphorylation of p120-catenin regulatory domain differently modulates its binding to RhoA

Mol Cell Biol. 2007 Mar;27(5):1745-57. doi: 10.1128/MCB.01974-06. Epub 2006 Dec 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Alternative Splicing
  • Animals
  • Catenins
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Delta Catenin
  • Fibroblasts / metabolism
  • Glutathione Transferase / metabolism
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Point Mutation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Tyrosine / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Catenins
  • Cell Adhesion Molecules
  • Fyb protein, mouse
  • Phosphoproteins
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Tyrosine
  • Glutathione Transferase
  • Protein-Tyrosine Kinases
  • rhoA GTP-Binding Protein
  • Delta Catenin