Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1 epsilon

Axin and the adenomatous polyposis coli protein (APC) interact to down-regu late the proto-oncogene beta -catenin. We show that transposition of an axi n-binding site can confer beta -catenin regulatory activity to a fragment o f APC normally lacking this activity. The fragment containing the axin-bind ing site also underwent hyperphosphorylation when coexpressed with axin. Th e phosphorylation did not require glycogen synthase kinase 3 beta but inste ad required casein kinase 1 epsilon, which bound directly to axin. Mutation of conserved serine residues in the beta -catenin regulatory motifs of APC interfered with both axin-dependent phosphorylation and phosphorylation by CKI epsilon and impaired the ability of APC to regulate beta -catenin. The se results suggest that the axin-dependent phosphorylation of APC is mediat ed in part by CKI epsilon and is involved in the regulation of APC function .