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Helicobacter pylori에 의한 위상피세포의 Matrix Metalloproteinase-I 생산과 Extracellular Signal-regulated Kinase 및 p38 Kinase의 역할: cagA 유전자 인산화의 기능

Other Titles
 Helicobacter pylori Induces Matrix Metalloproteinase-1 in AGS Cells via ERK and p38 Kinase Participation: Role of Tyrosine Phosphorylation of the cagA 
 이용찬  ;  김지현  ;  이인옥  ;  정재복  ;  Michael H. Pillinger  ;  Martin J. Blaser 
 Korean Journal of Helicobacter and Upper Gastrointestinal Research, Vol.6(1) : 35-42, 2006 
Journal Title
Korean Journal of Helicobacter and Upper Gastrointestinal Research
Issue Date
Helicobacter pylori ; Matrix metalloproteinase ; ERK ; p38
Background/Aims: Previous studies have highlighted the importance of matrix metalloproteinases (MMPs) in ulcerogenesis and recently MMPs is reported to be associated with cancer metastasis and carcinogenesis. Little is known about the role of CagA protein in MMPs secretion by H. pylori infected gastric epithelial cells. Therefore, we aimed to investigate the mechanism of MMP production in H. pylori-infected gastric epithelium. Furthermore, we asked whether the presence of tyrosine phosphorylation of CagA protein might play a role in MMP production by gastric epithelial cells.

Methods: A pair of isogenic cagA strains (one with tyrosine phosphorylation motif and the other without tyrosine phosphorylation motif; 147C and 147A) and cagA negative strain (8822) were used for H. pylori strains. MMP-1 production by AGS cells were measured by western blot and extracellular signal regulated kinase (ERK) and p38 kinase activation was analyzed in the presence of various inhibitors. Hummingbird phenotype induction was measured according to isogenic cagA H. pylori strains.

Results: CagA positive strain showed marked production of MMP-1 by gastric epithelial cells. Presence of tyrosine phosphorylation motif showed higher level of MMP-1 production. MMP-1 production by gastric epithelial cells required activation of the mitogen-activated protein kinases (MAPK), extracellular signal regulated kinase (ERK), and subsequent protein synthesis, but was down regulated by the alternate MAPK, p38 kinase.

Conclusions: Taken together, these data showed that secretion of MMP-1 by H. pylori infected gastric epithelial cells is differentially regulated by ERK and p38 kinase and dependent of tyrosine phosphorylation of CagA.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Jie-Hyun(김지현) ORCID logo https://orcid.org/0000-0002-9198-3326
Lee, Yong Chan(이용찬) ORCID logo https://orcid.org/0000-0001-8800-6906
Lee, In Ok(이인옥)
Chung, Jae Bock(정재복)
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