CK1ε and p120-catenin control Ror2 function in noncanonical wnt signaling

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Curto, Josué
• dc.contributor.author Valle Pérez, Beatriz del
• dc.contributor.author Villarroel, Aida
• dc.contributor.author Fuertes, Guillem
• dc.contributor.author Vinyoles, Meritxell
• dc.contributor.author Peña, Raúl
• dc.contributor.author García de Herreros, Antonio
• dc.contributor.author Duñach, Mireia
• dc.date.accessioned 2018-10-31T13:20:24Z
• dc.date.available 2018-10-31T13:20:24Z
• dc.date.issued 2018
• dc.description.abstract Canonical and noncanonical Wnt pathways share some common elements but differ in the responses they evoke. Similar to Wnt ligands acting through the canonical pathway, Wnts that activate the noncanonical signaling, such as Wnt5a, promote Disheveled (Dvl) phosphorylation and its binding to the Frizzled (Fz) Wnt receptor complex. The protein kinase CK1ε is required for Dvl/Fz association in both canonical and noncanonical signaling. Here we show that differently to its binding to canonical Wnt receptor complex, CK1ε does not require p120‐catenin for the association with the Wnt5a co‐receptor Ror2. Wnt5a promotes the formation of the Ror2–Fz complex and enables the activation of Ror2‐bound CK1ε by Fz‐associated protein phosphatase 2A. Moreover, CK1ε also regulates Ror2 protein levels; CK1ε association stabilizes Ror2, which undergoes lysosomal‐dependent degradation in the absence of this kinase. Although p120‐catenin is not required for CK1ε association with Ror2, it also participates in this signaling pathway as p120‐catenin binds and maintains Ror2 at the plasma membrane; in p120‐depleted cells, Ror2 is rapidly internalized through a clathrin‐dependent mechanism. Accordingly, downregulation of p120‐catenin or CK1ε affects late responses to Wnt5a that are also sensitive to Ror2, such as SIAH2 transcription, cell invasion, or cortical actin polarization. Our results explain how CK1ε is activated by noncanonical Wnt and identify p120‐catenin and CK1ε as two critical factors controlling Ror2 function
• dc.description.sponsorship This research was funded by grants from the Ministerio de Economía y Competitividad (MINECO) (BFU2015‐65153‐R co‐funded by Fondo Europeo de Desarrollo Regional‐FEDER‐UE) to MD, Agencia Estatal de Investigación (AEI) and FEDER (SAF2016‐76461‐R) to AGH and Fundació La Marató de TV3 (20120130) to MD and AGH. We also appreciate support from ICREA Academia, Generalitat de Catalunya (2014 SGR 32), and Instituto de Salud Carlos III (PIE15/00008). GF was recipient of a predoctoral fellowship from FPI
• dc.format.mimetype application/pdf
• dc.identifier.citation Curto J, Del Valle-Pérez B, Villarroel A, Fuertes G, Vinyoles M, Peña R et al. CK1ε and p120-catenin control Ror2 function in noncanonical wnt signaling. Mol Oncol. 2018;12(5):611-29. DOI: 10.1002/1878-0261.12184
• dc.identifier.doi http://dx.doi.org/10.1002/1878-0261.12184
• dc.identifier.issn 1574-7891
• dc.identifier.uri http://hdl.handle.net/10230/35686
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Molecular Oncology. 2018;12(5):611-29
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015‐65153‐R
• dc.rights © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword CK1ε
• dc.subject.keyword Noncanonical wnt
• dc.subject.keyword p120-catenin
• dc.subject.keyword Ror2
• dc.title CK1ε and p120-catenin control Ror2 function in noncanonical wnt signaling
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion