Activation of CK1 epsilon by PP2A/PR61 epsilon is required for the initiation of Wnt signaling

作者：Vinyoles M; Del Valle Perez B; Curto J; Padilla M; Villarroel A; Yang J; de Herreros A G^*; Dunach M^*

来源：Oncogene, 2017, 36(3): 429-438.

DOI：10.1038/onc.2016.209

Canonical Wnt signaling induces the stabilization of beta-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 coreceptor and the formation of a complex comprising Dvl-2, Axin and protein kinases CK1 alpha, epsilon, gamma and GSK3. Among these, activation of CK1 epsilon, constitutively bound to LRP5/6 through p120-catenin, is required for the association of the rest of the components. We describe here that CK1 epsilon is activated by the PP2A/PR61 epsilon phosphatase. Binding of Wnt ligands promotes the interaction of LRP5/6-associated CK1 epsilon with Frizzled-bound PR61 epsilon regulatory subunit, facilitating the access of PP2A catalytic subunit to CK1 epsilon 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.

• 出版日期2017-1-19