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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Bacterial / genetics
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Antigens, Bacterial / metabolism*
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Cells, Cultured
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Cytokine Receptor gp130 / genetics
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Cytokine Receptor gp130 / metabolism*
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Epithelial Cells / metabolism*
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Epithelial Cells / microbiology
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Gastric Mucosa / metabolism
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Helicobacter pylori / genetics
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Helicobacter pylori / metabolism*
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Humans
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Janus Kinases / genetics
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Janus Kinases / metabolism*
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MAP Kinase Signaling System*
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Phosphorylation / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism*
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Stomach / microbiology
Substances
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Antigens, Bacterial
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Bacterial Proteins
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IL6ST protein, human
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Il6st protein, mouse
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, mouse
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cagA protein, Helicobacter pylori
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Cytokine Receptor gp130
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Janus Kinases
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Mitogen-Activated Protein Kinase 3
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Protein Tyrosine Phosphatase, Non-Receptor Type 11