Interaction of PKCα with the armadillo repeats facilitates the N-terminal phosphorylation of ß-catenin.

ABSTRACT

Protein kinase Cα (PKCα) phosphorylates the Ser33/37/Thr41 residues of ß-catenin, which lacks a typical PKCα canonical sequence, but little is known about its underlying mechanism. Here we showed that Ser33/Ser37/Thr41 of ß-catenin fragments encompassing the armadillo repeats 1-5 (ß-catenin1-781, ß-catenin1-682, and ß-catenin1-422) are phosphorylated by PKCα whereas ß-catenin1-138 lacking these repeats is not phosphorylated. Binding-site analysis revealed that PKCα directly interacts with ß-catenin through the sites on the armadillo repeats 1-5. In addition, axin fragments (365-500), which interacts with ß-catenin through armadillo repeats 3-5, disrupted PKCα/ß-catenin association and inhibited ß-catenin phosphorylation by PKCα. In HEK293 cells, the levels of ß-catenin1-781 and ß-catenin1-422 were decreased whereas the amount of ß-catenin1-138 was unchanged by pharmacological stimulation of PKCα. Our results suggest that the association of PKCα with the armadillo repeats of ß-catenin placed the Ser33/37/Thr41 residues of ß-catenin in close proximity to PKCα, thereby facilitating PKCα-mediated ß-catenin phosphorylation.