Helicobacter pylori modulates host cell survival regulation through the serine-threonine kinase, 3-phosphoinositide dependent kinase 1 (PDK-1)

BMC Microbiology

Research Article

Marygorret Obonyo¹  Charles C. King² 

[1] Department of Medicine, University of California, La Jolla, 92093, San Diego, CA, USA;Pediatric Diabetes Research Center, University of California, La Jolla, 92093, San Diego, CA, USA;

关键词: Helicobacter pylori;    PDK-1;    Akt;    AGS cells;   

DOI  :  10.1186/s12866-015-0543-0

 received in 2015-05-01, accepted in 2015-10-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundHelicobacter pylori (H. pylori) infection affects cell survival signaling pathways including cell apoptosis and proliferation, which are considered risk factors for the development of gastric cancer when unregulated. In the present study, we investigated the effect of H. pylori infection on the phosphorylation state of 3-phosphoinositide-dependent kinase-1 (PDK-1), a master kinase that regulates phosphorylation of Akt (also known as protein kinase B, PKB) and cell survival. MethodsThe activity of PDK-1 was examined in human gastric epithelial cells incubated in the presence or absence of different H. pylori strains. In addition, the role of H. pylori type IV secretion system and the mechanism of H. pylori effect on PDK-1 activity was examined.ResultsIn the presence of H. pylori, phosphorylation of the activation loop (serine 241) PDK-1 was rapidly lost suggesting that dephosphorylation of PDK-1 is a target for H. pylori to modulate cell survival. The extent of dephosphorylation was strain dependent with H. pylori 60190 being the most effective. H. pylori infection of gastric epithelial cells resulted in altered phosphorylation and degradation of Akt, suggesting that PDK-1 dephosphorylation affects cell survival pathways and thereby may contribute to disease pathogenesis.ConclusionWe propose that dephosphorylation of PDK-1 and the resulting changes to Akt phosphorylation is one of the mechanisms by which infection with H. pylori alter the balance between apoptosis and cell proliferation and identify a host molecular mechanism regulated by H. pylori that ultimately contributes to carcinogenesis. Our studies therefore provide insights into one of the mechanisms by which H. pylori infection contributes to gastric cancer by regulating the activity of a cell survival signaling pathway.

【 授权许可】

CC BY   
© King and Obonyo. 2015