1 / 15

SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein

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

keely
Download Presentation

SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

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. Introduction 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

  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 WT:wild type PR:phosphorylation resistance HA:hemagglutinin tag Potential tyrosine phosphorylation site:Glu-Pro-Ile-Tyr-Ala (EPIYA) Expression of CagA

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

  12. Role of SHP-2 induce hummingbird phenotype

  13. Myr:Membrane-localization signal sequence (myristoylation signal sequence of v-Src) Role of SHP-2 induce hummingbird phenotype

  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

  15. Thanks

More Related