Casein Kinase Iε in the Wnt Pathway: Regulation of β -Catenin Function

Wnt and its intracellular effector β -catenin regulate developmental and oncogenic processes. Using expression cloning to identify novel components of the Wnt pathway, we isolated casein kinase Iε (CKIε). CKIε mimicked Wnt in inducing a secondary axis in Xenopus, stabilizing β -catenin, and stimulating gene transcription in cells. Inhibition of endogenous CKIε by kinase-defective CKIε or CKIε antisense-oligonucleotides attenuated Wnt signaling. CKIε was in a complex with axin and other downstream components of the Wnt pathway, including Dishevelled. CKIε appears to be a positive regulator of the pathway and a link between upstream signals and the complexes that regulate β -catenin.