title: 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.
authors: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea; Research Institute for Basic Science, Sogang University, 35 Baekbeom-ro (Sinsu-dong), Mapo-gu, Seoul 121-742, Republic of Korea.
authors: Jungsug
authors: J
authors: Gwak
authors: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors: Young-Sun
authors: YS
authors: Yoo
authors: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea.
authors: Yang Ji
authors: YJ
authors: Choi
authors: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea. Electronic address: ohsa@kookmin.ac.kr.
authors: Sangtaek
authors: S
authors: Oh
mesh_terms: D051186:Armadillo Domain Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051186:Armadillo Domain Proteins; D051176:beta Catenin; D051571:Protein Kinase C-alpha
keywords: Phosphorylation; Protein degradation; Protein kinase Cα; β-Catenin