Helicobacter pylori suppresses glycogen synthase kinase 3beta to promote beta-catenin activity.
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 beta-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 beta-catenin and to up-regulation of lymphoid enhancer-binding factor/T cell factor (LEF/TCF)-dependent transcription. The impaired Ser/Thr phosphorylation of beta-catenin was accompanied by an increase of glycogen synthase kinase 3beta 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 beta-catenin. We conclude that glycogen synthase kinase 3beta activity exerts an important role in beta-catenin regulation and LEF/TCF transactivation in H. pylori-infected Madin-Darby canine kidney cells.
Sokolova
Olga
O
Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg 39120, Germany.
Bozko
Przemyslaw M
PM
Naumann
Michael
M
D000818:Animals; D002460:Cell Line; D019938:Cyclin D1 / Q000096:biosynthesis; D004285:Dogs; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D016481:Helicobacter Infections / Q000175:diagnosis / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
D051821:Lymphoid Enhancer-Binding Factor 1; D034741:RNA, Small Interfering; D051176:beta Catenin; D019938:Cyclin D1; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
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