Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling
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- dc.contributor.author Vinyoles, Meritxell
- dc.contributor.author Valle Pérez, Beatriz del
- dc.contributor.author Curto, Josué
- dc.contributor.author Padilla, Mary
- dc.contributor.author Villarroel, Aida
- dc.contributor.author Yang, J.Y.
- dc.contributor.author García de Herreros, Antonio
- dc.contributor.author Duñach, Mireia
- dc.date.accessioned 2018-11-30T09:43:16Z
- dc.date.available 2018-11-30T09:43:16Z
- dc.date.issued 2017
- dc.description.abstract Canonical Wnt signaling induces the stabilization of β-catenin, its translocation to the nucleus and the activation of target promoters. This pathway is initiated by the binding of Wnt ligands to the Frizzled receptor, the association of the LRP5/6 co-receptor and the formation of a complex comprising Dvl-2, Axin and protein kinases CK1α, ɛ, γ and GSK3. Among these, activation of CK1ɛ, constitutively bound to LRP5/6 through p120-catenin, is required for the association of the rest of the components. We describe here that CK1ɛ is activated by the PP2A/PR61ɛ phosphatase. Binding of Wnt ligands promotes the interaction of LRP5/6-associated CK1ɛ with Frizzled-bound PR61ɛ regulatory subunit, facilitating the access of PP2A catalytic subunit to CK1ɛ and its activation, what enables the recruitment of Dvl-2 to the receptor complex and the initiation of the Wnt pathway. Our results uncover the mechanism of activation of the canonical Wnt pathway by its ligands.
- dc.description.sponsorship This work was funded by grants from the Ministerio de Economía y Competitividad (BFU2012-31554 and BFU2015-65153-R, both MINECO/FEDER, to MD and SAF2013-48849-C2-R1 to AGH) and Fundació La Marató de TV3 (120130) to MD and AGH. Support from ICREA Academia, 2014SGR-32 from Generalitat de Catalunya and ISCIII/FEDER (RD12/0036/005) is also appreciated
- dc.format.mimetype application/pdf
- dc.identifier.citation Vinyoles M, Del Valle-Pérez B, Curto J, Padilla M, Villarroel A, Yang J et al. Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling. Oncogene. 2017 Jan 19;36(3):429-38. DOI: 10.1038/onc.2016.209
- dc.identifier.doi http://dx.doi.org/10.1038/onc.2016.209
- dc.identifier.issn 0950-9232
- dc.identifier.uri http://hdl.handle.net/10230/35913
- dc.language.iso eng
- dc.publisher Springer Nature
- dc.relation.ispartof Oncogene. 2017 Jan 19;36(3):429-38
- dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-31554
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-65153-R
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-48849-C2-R1
- dc.rights © 2017 Macmillan Publishers Limited, part of Springer Nature
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Fosfoproteïnes fosfatases
- dc.subject.other Interacció cel·lular
- dc.title Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion