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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 Proteïnes quinases -- Metabolisme Cadherines CK1 E-cadherin Wnt p120-catenin 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. This study was supported by grants awarded by the Ministerio de Ciencia e Innovación: BFU2006-03203 and BFU2009-07578 to M.D. and SAF2006-00339 to A.G.H. Partial support from the Instituto Carlos III (RD06/0020/0040) and the Generalitat de Catalunya (2009SGR867 and 2009SGR585) is also appreciated. D.C. and G.V. were supported by predoctoral fellowships from the Ministerio de Educación and E.L., from the UAB. 2016-01-15T19:41:45Z 2016-01-15T19:41:45Z 2010 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Journal of cell science. 2010; 123(Pt 15): 2621-2631 info:eu-repo/grantAgreement/ES/2PN/BFU2006-03203 info:eu-repo/grantAgreement/ES/2PN/SAF2006-00339 info:eu-repo/grantAgreement/ES/3PN/BFU2009-07578 © Company of Biologists http://jcs.biologists.org/content/joces/123/15/2621.full.pdf DOI 10.1242/jcs.067512 info:eu-repo/semantics/openAccess Company of Biologists