Título:
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Activation of CK1ɛ by PP2A/PR61ɛ is required for the initiation of Wnt signaling
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Autor/a:
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Vinyoles, Meritxell; Valle Pérez, Beatriz del; Curto, Josué; Padilla, Mary; Villarroel, Aida; Yang, J.Y.; García de Herreros, Antonio; Duñach, Mireia
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Abstract:
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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. |
Abstract:
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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 |
Materia(s):
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-Fosfoproteïnes fosfatases -Interacció cel·lular |
Derechos:
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© 2017 Macmillan Publishers Limited, part of Springer Nature
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Tipo de documento:
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Artículo Artículo - Versión aceptada |
Editor:
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Springer Nature
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