SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein Hideaki...
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Transcript of SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein Hideaki...
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SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori
CagA Protein Hideaki Higashi, Ryouhei Tsutsumi, Syuichi Muto,Toshiro Sugiyama, T
akeshi Azuma, Masahiro Asaka, Masanori Hatakeyama
Science, Vol. 295, 683-686, January 25, 2002
Speaker:林智健Professor:吳夙欽
2002/10/01
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Helicobacter pylori (H. pylori)
• Gram-negative bacterium• Cause chronic gastritis and gastrod
uodenal ulcers• Associate with the gastric cancer a
nd MALT lymphoma• Infection half of the world’s populati
on
Introduction
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Cytotoxin associated gene A (CagA)
• 128 ~ 145 kDa protein• Signal the nucleus to release I L-8• Inject into host cell by type IV secretion system• Tyrosine phosphorylation in host cell• High immunogenicity
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How H. pylori survives in human stomach
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The secretion system of H. pylori injects CagA into the host cell
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SH2 protein tyrosine phosphatase 2 (SHP-2)
• Cytoplasmic tyrosine phosphatase• SH2: src homology 2 domains
binding to protein
• PTP: protein tyrosine phosphatase
catalysis of protein tyrosine phosphorylation
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Results and discussion
Expression of CagA
WT: wild type
PR: phosphorylation resistance
HA: hemagglutinin tag
Potential tyrosine phosphorylation
site: Glu-Pro-Ile-Tyr-Ala (EPIYA)
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Hummingbird phenotype (growth-factor-like phenotype)Hepatocyte growth factor
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Interaction between CagA and SHP-2
IP: immunoprecipitate
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Myc:Myc tag
∆PD-Myc: del PTP domain
∆SH2-Myc: del SH2 domain
Interaction between CagA and SHP-2
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Activation of SHP-2 by CagA
Model for activation and inhibition
of SHP2
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Role of SHP-2 induce hummingbird phenotype
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Role of SHP-2 induce hummingbird phenotype
Myr:Membrane-localization
signal sequence (myristoylation
signal sequence of v-Src)
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Conclusion
• Wild-Type CagA induce a growth factor-like response (hummingbird phenotype) but tyrosine-phosphorylation resistance CagA
• CagA formed a physical complex with SH2 domain of SHP-2 protein
• Disruption of the CagA–SHP-2 complex abolished the CagA-dependent cellular response.
• SHP-2 lack membrane-targeting signal sequence incapable induce cellular morphological change
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Thanks