Axin-dependent Phosphorylation of the Adenomatous Polyposis Coli Protein Mediated by Casein Kinase 1ε

Abstract

Axin and the adenomatous polyposis coli protein (APC) interact to down-regulate the proto-oncogene β-catenin. We show that transposition of an axin-binding site can confer β-catenin regulatory activity to a fragment of APC normally lacking this activity. The fragment containing the axin-binding site also underwent hyperphosphorylation when coexpressed with axin. The phosphorylation did not require glycogen synthase kinase 3β but instead required casein kinase 1ε, which bound directly to axin. Mutation of conserved serine residues in the β-catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKIε and impaired the ability of APC to regulate β-catenin. These results suggest that the axin-dependent phosphorylation of APC is mediated in part by CKIε and is involved in the regulation of APC function.