A p120-catenin-CK1epsilon complex regulates Wnt signaling

Casagolda, David; Valle Pérez, Beatriz del; Valls, Gabriela; Lugilde, Ero; Vinyoles, Meritxell; Casado Vela, Juan; Solanas, Guiomar; Batlle Gómez, Eduard; Reynolds, Albert B.; Casal, José Ignacio; García de Herreros, Antonio; Duñach, Mireia

doi:http://dx.doi.org/10.1242/jcs.067512

A p120-catenin-CK1epsilon complex regulates Wnt signaling

Citation

Casagolda D, Del Valle-Pérez B, Valls G, Lugilde E, Vinyoles M, Casado-Vela J. A p120-catenin-CK1epsilon complex regulates Wnt signaling. Journal of cell science. 2010; 123(Pt 15): 2621-2631. DOI 10.1242/jcs.067512

Abstract

p120-catenin is an E-cadherin-associated protein that modulates E-cadherin function and stability. We describe here that p120-catenin is required for Wnt pathway signaling. p120-catenin binds and is phosphorylated by CK1ε in response to Wnt3a. p120-catenin also associates to the Wnt co-receptor LRP5/6, an interaction mediated by E-cadherin, showing an unexpected physical link between adherens junctions and a Wnt receptor. Depletion of p120-catenin abolishes CK1ε binding to LRP5/6 and prevents CK1ε activation upon Wnt3a stimulation. Elimination of p120-catenin also inhibits early responses to Wnt, such as LRP5/6 and Dvl-2 phosphorylation and axin recruitment to the signalosome, as well as later effects, such as β-catenin stabilization. Moreover, since CK1ε is also required for E-cadherin phosphorylation, a modification that decreases the affinity for β-catenin, p120-catenin depletion prevents the increase in β-catenin transcriptional activity even in the absence of β-catenin degradation. Therefore, these results demonstrate a novel and crucial function of p120-catenin in Wnt signaling and unveil additional points of regulation by this factor of β-catenin transcriptional activity different of β-catenin stability.