Activation of CK1ϵ by PP2A/PR61ϵ is required for the initiation of Wnt signaling

M. Vinyoles, B. Del Valle-Pérez, J. Curto, M. Padilla, A. Villarroel, J. Yang, A. G. De Herreros, M. Duñach

Research output: Contribution to journalArticlepeer-review


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, ϵ, γ and GSK3. Among these, activation of CK1ϵ, constitutively bound to LRP5/6 through p120-catenin, is required for the association of the rest of the components. We describe here that CK1ϵ is activated by the PP2A/PR61ϵ phosphatase. Binding of Wnt ligands promotes the interaction of LRP5/6-associated CK1ϵ with Frizzled-bound PR61ϵ regulatory subunit, facilitating the access of PP2A catalytic subunit to CK1ϵ 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.

Original languageEnglish (US)
Pages (from-to)429-438
Number of pages10
Issue number3
StatePublished - Jan 19 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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