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Helicobacter pylori CagA phosphorylation status determines the gp130-activated SHP2/ERK and JAK/STAT signal transduction pathways in gastric epithelial cells

Authors
 In Ohk Lee  ;  Jie Hyun Kim  ;  Yeun Jung Choi  ;  Michael H. Pillinger  ;  Seok-Yong Kim  ;  Martin J. Blaser  ;  Yong Chan Lee 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.285(21) : 16042-16050, 2010 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2010
MeSH
Animals ; Antigens, Bacterial/genetics ; Antigens, Bacterial/metabolism* ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism* ; Cells, Cultured ; Cytokine Receptor gp130/genetics ; Cytokine Receptor gp130/metabolism* ; Epithelial Cells/metabolism* ; Epithelial Cells/microbiology ; Helicobacter pylori/genetics ; Helicobacter pylori/metabolism* ; Humans ; Janus Kinases/genetics ; Janus Kinases/metabolism* ; MAP Kinase Signaling System* ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase 3/genetics ; Mitogen-Activated Protein Kinase 3/metabolism* ; Phosphorylation/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism* ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism* ; Stomach/metabolism ; Stomach/microbiology
Abstract
The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling
Files in This Item:
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DOI
10.1074/jbc.M110.111054
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 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
Choi, Youn Jeong(최연정)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101116
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