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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,

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Presentation on theme: "SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein Hideaki Higashi, Ryouhei Tsutsumi, Syuichi Muto,Toshiro Sugiyama,"— Presentation transcript:

1 SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein Hideaki Higashi, Ryouhei Tsutsumi, Syuichi Muto,Toshiro Sugiyama, Takeshi Azuma, Masahiro Asaka, Masanori Hatakeyama Science, Vol. 295, 683-686, January 25, 2002 Speaker ：林智健 Professor ：吳夙欽 2002/10/01

2 Helicobacter pylori (H. pylori) Gram-negative bacterium Cause chronic gastritis and gastroduodenal ulcers Associate with the gastric cancer and MALT lymphoma Infection half of the world’s population Introduction

3 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

4 How H. pylori survives in human stomach

5 The secretion system of H. pylori injects CagA into the host cell

6 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

7 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)

8 Hummingbird phenotype (growth-factor-like phenotype) Hepatocyte growth factor

9 Interaction between CagA and SHP-2 IP ： immunoprecipitate

10 Myc ： Myc tag ∆PD-Myc ： del PTP domain ∆SH2-Myc ： del SH2 domain Interaction between CagA and SHP-2

11 Activation of SHP-2 by CagA Model for activation and inhibition of SHP2

12 Role of SHP-2 induce hummingbird phenotype

13 Myr ： Membrane-localization signal sequence (myristoylation signal sequence of v-Src)

14 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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