M. Asano (Tohoku Univ.) M. Senami (Kyoto Univ.) H. Sugiyama (Ritsumeikan Univ.)
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...
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
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
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
How H. pylori survives in human stomach
The secretion system of H. pylori injects CagA into the host cell
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
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)
Hummingbird phenotype (growth-factor-like phenotype)Hepatocyte growth factor
Interaction between CagA and SHP-2
IP: immunoprecipitate
Myc:Myc tag
∆PD-Myc: del PTP domain
∆SH2-Myc: del SH2 domain
Interaction between CagA and SHP-2
Activation of SHP-2 by CagA
Model for activation and inhibition
of SHP2
Role of SHP-2 induce hummingbird phenotype
Role of SHP-2 induce hummingbird phenotype
Myr:Membrane-localization
signal sequence (myristoylation
signal sequence of v-Src)
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
Thanks