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

Abstract

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