Fig. 7. Model for regulation of CK1 activity by activation of group I mGluRs.

DHPG activates group I mGluRs that are coupled to PLCβ via G_q. Activation of PLCβ generates IP₃, and IP₃ binds to IP₃ receptors on the endoplasmic reticulum and releases Ca²⁺ into the cytosol. Elevated intracellular Ca²⁺actives the Ca²⁺-dependent phosphatase calcineurin, which in turn dephosphorylates the regulatory autophosphorylation sites on CKIε. CKIε is transiently activated, but gradual autophosphorylation restores the inhibited level of kinase activity. A site that is basally phosphorylated is likely to be present within the kinase domain but does not appear to regulate enzyme activity.