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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.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.issn 0950-9232
dc.identifier.uri http://hdl.handle.net/10230/35913
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.language.iso eng
dc.publisher Springer Nature
dc.relation.ispartof Oncogene. 2017 Jan 19;36(3):429-38
dc.rights © 2017 Macmillan Publishers Limited, part of Springer Nature
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.identifier.doi http://dx.doi.org/10.1038/onc.2016.209
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.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion


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