QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online November 8, 2006
doi: 10.1242/10.1242/jcs.03256

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gwak, J. Articles by Oh, S. Search for Related Content PubMed PubMed Citation Articles by Gwak, J. Articles by Oh, S.

Protein-kinase-C-mediated ß-catenin phosphorylation negatively regulates the Wnt/ß-catenin pathway

¹ PharmcoGenomics Research Center, Inje University, Busan 614-735, Korea
² Department of Biotechnology and Bioengineering, Dong-Eui University, Busan 614-714, Korea
³ Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
⁴ Department of Clinical Pharmacology, Busan Paik Hospital, Inje University College of Medicine, Busan 614-735, Korea
⁵ Department of Pharmacology, Inje University College of Medicine, Busan 614-735, Korea
⁶ CGK Co. Ltd, Daejeon 305-701, Korea

^* Authors for correspondence (e-mail: phshinjg{at}inje.ac.kr; ohsa{at}inje.ac.kr)

Accepted 4 September 2006

Normally, the Wnt/ß-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/ß-catenin pathway is the amino-terminal phosphorylation of ß-catenin, marking it for proteasomal degradation. Here we present small-molecule-based identification of protein kinase C (PKC)-mediated ß-catenin phosphorylation as a novel mechanism regulating the Wnt/ß-catenin pathway. We used a cell-based chemical screen to identify A23187, which inhibits the Wnt/ß-catenin pathway. PKC was activated by A23187 treatment and subsequently phosphorylated N-terminal serine (Ser) residues of ß-catenin, which promoted ß-catenin degradation. Moreover, the depletion of PKC inhibited the phosphorylation and degradation of ß-catenin. Therefore, our findings suggest that the PKC pathway negatively regulates the ß-catenin level outside of the Wnt/ß-catenin pathway.

Key words: Wnt/ß-catenin pathway, Protein kinase C, Phosphorylation, Degradation

This article has been cited by other articles:

				G.-Y. Song, J.-H. Lee, M. Cho, B.-S. Park, D.-E. Kim, and S. Oh Decursin Suppresses Human Androgen-Independent PC3 Prostate Cancer Cell Proliferation by Promoting the Degradation of beta-Catenin Mol. Pharmacol., December 1, 2007; 72(6): 1599 - 1606. [Abstract] [Full Text] [PDF]

				R. E. Slager, D. S. Allen-Gipson, A. Sammut, A. Heires, J. DeVasure, S. Von Essen, D. J. Romberger, and T. A. Wyatt Hog barn dust slows airway epithelial cell migration in vitro through a PKC{alpha}-dependent mechanism Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1469 - L1474. [Abstract] [Full Text] [PDF]

				R. L. Daugherty and C. J. Gottardi Phospho-regulation of {beta}-Catenin Adhesion and Signaling Functions Physiology, October 1, 2007; 22(5): 303 - 309. [Abstract] [Full Text] [PDF]