p120 Catenin-Associated Fer and Fyn Tyrosine Kinases Regulate β-Catenin Tyr-142 Phosphorylation and β-Catenin-α-Catenin Interaction

Abstract

β-Catenin has a key role in the formation of adherens junction through its interactions with E-cadherin and α-catenin. We show here that interaction of β-catenin with α-catenin is regulated by the phosphorylation of β-catenin Tyr-142. This residue can be phosphorylated in vitro by Fer or Fyn tyrosine kinases. Transfection of these kinases to epithelial cells disrupted the association between both catenins. We have also examined whether these kinases are involved in the regulation of this interaction by K-ras. Stable transfectants of the K-ras oncogene in intestinal epithelial IEC18 cells were generated which show little α-catenin-β-catenin association with respect to control clones; this effect is accompanied by increased Tyr-142 phosphorylation and activation of Fer and Fyn kinases. As reported for Fer, Fyn kinase is constitutively bound to p120 catenin; expression of K-ras induces the phosphorylation of p120 catenin on tyrosine residues increasing its affinity for E-cadherin and, consequently, promotes the association of Fyn with the adherens junction complex. Yes tyrosine kinase also binds to p120 catenin but only upon activation, and stimulates Fer and Fyn tyrosine kinases. These results indicate that p120 catenin acts as a docking protein facilitating the activation of Fer/Fyn tyrosine kinases by Yes and demonstrate the role of these p120 catenin-associated kinases in the regulation of β-catenin-α-catenin interaction.

ACKNOWLEDGMENTS

We thank Albert B. Reynolds, Ana Clara Carrera, José María Rojas, and Marius Sudol for providing plasmids and Alberto Muñoz for his help in the generation of the K-ras transfectant clones.

This work was supported by grants 01/045-00 (from Fundació La Caixa) to A.G.H.; PM-99-0132 and PM99-0064 (from Ministerio de Ciencia y Tecnología) to A.G.H. and M.D., respectively; and 2001SGR00410 and 2001SGR00197 (from Direcció General de Recerca). J.C. and S.M. were recipients of predoctoral fellowships from the Ministerio de Educación y Ciencia and UAB, respectively.