FIGURE 9.
Model for the function of casein kinases in Dvl biology. Casein kinase 2 (and probably also PAR1 and its mammalian homologues) behave like constitutively active kinases. Under normal conditions CK2 phosphorylates Dvl in the basic domain/PDZ (bPDZ) to trigger formation of P-Dvl. P- Dvl was then subject to phosphorylation by CK1δ/ϵ, which becomes activated upon Wnt stimulation. CK1δ/ϵ phosphorylation of P-Dvl in the PDZ and/or Pro-rich region of Dvl allows recruitment of axin and phosphorylation of Lrp6 (usually detected after 10–15 min) and an executive phase of pathway activation (TCF/LEF-driven transcription), which is dependent on the DIX domains. Dvl in these functional states was capable of polymerization with an electrophoretic migration that resembles P-Dvl. Further phosphorylation of Dvl by CK1 led to the formation of PS-Dvl (usually detected 30–45 min after Wnt stimulation) and ultimately resulted in the inactivation of Dvl in the β-catenin pathway. This functional state of Dvl, which requires the C terminus of Dvl, leads to Dvl depolymerization and uniform subcellular distribution. Using this mechanism, CK1δ/ϵ can control both the activation and the termination of the pathway.