Helicobacter pylori Suppresses Glycogen Synthase Kinase 3β to Promote β-Catenin Activity

• Published in: The Journal of biological chemistry Vol. 283; no. 43; pp. 29367 - 29374
• Main Authors: Sokolova, Olga, Bozko, Przemyslaw M., Naumann, Michael
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 24.10.2008; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M801818200

The human pathogen Helicobacter pylori influences cell adhesion, proliferation, and apoptosis and is involved in gastric adenocarcinoma formation. In our study we analyzed the impact of H. pylori infection on the regulation of β-catenin, which plays a central role in both cell adhesion and tumorigenesis. Infection of Madin-Darby canine kidney cells with H. pylori led to suppression of Ser/Thr phosphorylation and ubiquitin-dependent degradation of β-catenin and to up-regulation of lymphoid enhancer-binding factor/T cell factor (LEF/TCF)-dependent transcription. The impaired Ser/Thr phosphorylation of β-catenin was accompanied by an increase of glycogen synthase kinase 3β phosphorylation. Inhibition of Akt kinase, an up-stream regulator of glycogen synthase kinase 3, by a specific inhibitor Akti-1/2 or depletion of Akt with siRNA restored Ser/Thr phosphorylation of β-catenin. We conclude that glycogen synthase kinase 3β activity exerts an important role in β-catenin regulation and LEF/TCF transactivation in H. pylori-infected Madin-Darby canine kidney cells.