Casein kinase I« in the Wnt pathway: Regulation of b-catenin function

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