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PMID: 18772141 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Helicobacter pylori suppresses glycogen synthase kinase 3beta to promote beta-catenin activity.

The Journal of biological chemistry ·Vol. 283 ·No. 43 ·2008-10-24 ·Pages 29367-74

Sokolova O, Bozko PM, Naumann M

Abstract

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.

MeSH Terms
Animals Cell Line Cyclin D1/biosynthesis Dogs Glycogen Synthase Kinase 3/metabolism Glycogen Synthase Kinase 3 beta Helicobacter Infections/diagnosis,metabolism Helicobacter pylori/metabolism Lymphoid Enhancer-Binding Factor 1/metabolism Models, Biological Phosphorylation Proto-Oncogene Proteins c-akt/metabolism RNA, Small Interfering/metabolism Transcriptional Activation Up-Regulation beta Catenin/metabolism
Chemicals
Lymphoid Enhancer-Binding Factor 1 RNA, Small Interfering beta Catenin Cyclin D1 GSK3B protein, human Glycogen Synthase Kinase 3 beta Proto-Oncogene Proteins c-akt Glycogen Synthase Kinase 3
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sokolova Olga
Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg 39120, Germany.
Bozko Przemyslaw M
Naumann Michael
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M801818200
Published
2008-10-24
Epub
2008-00-04
Pages
29367-74
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2662023
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M801818200 PMC Full Text View journal details
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