연구소 소식

1. 논문 제목: Protein-kinase-C-mediated b-catenin phosphorylation negatively regulates the Wnt/b-catenin pathway
2. 게재지: Journal of Cell Science
3. 저자: 곽정숙, 조문주, 김은영, 이상섭, 오상택, 신재국
3. Summary:
Normally, the Wnt/b-catenin pathway controls developmental processes and homeostasis, but abnormal activation of this pathway is a frequent event during the development of cancer. The key mechanism in regulation of the Wnt/b-catenin pathway is the amino-terminal phosphorylation of b-catenin, marking it for proteasomal degradation. Here we present small-molecule-based identification of protein kinase C (PKC)-mediated bcatenin phosphorylation as a novel mechanism regulating the Wnt/b-catenin pathway. We used a cell-based chemical screen to identify A23187, which inhibits the Wnt/b-catenin pathway. PKC was activated by A23187 treatment and subsequently phosphorylated N-terminal serine (Ser) residues of b-catenin, which promoted b-catenin degradation. Moreover, the depletion of PKCa inhibited the phosphorylation and degradation of b-catenin. Therefore, our findings suggest that the PKC pathway negatively regulates the b-catenin level outside of the Wnt/b-catenin pathway.