Title: SHP2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein
1SHP-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???
- Professor???
- 2002/10/01
2Introduction
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 worlds population
3Cytotoxin 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
4How H. pylori survives in human stomach
5The secretion system of H. pylori injects CagA
into the host cell
6SH2 protein tyrosine phosphatase 2 (SHP-2)
- Cytoplasmic tyrosine phosphatase
- SH2src homology 2 domains
- binding to protein
- PTPprotein tyrosine phosphatase
- catalysis of protein tyrosine
phosphorylation
7Results and discussion
WTwild type PRphosphorylation
resistance HAhemagglutinin tag Potential
tyrosine phosphorylation siteGlu-Pro-Ile-Tyr-Ala
(EPIYA)
Expression of CagA
8Hummingbird phenotype (growth-factor-like
phenotype)Hepatocyte growth factor
9Interaction between CagA and SHP-2
IPimmunoprecipitate
10MycMyc tag ?PD-Mycdel PTP domain ?SH2-Mycdel
SH2 domain
Interaction between CagA and SHP-2
11Model for activation and inhibition of SHP2
Activation of SHP-2 by CagA
12Role of SHP-2 induce hummingbird phenotype
13MyrMembrane-localization signal sequence
(myristoylation signal sequence of v-Src)
Role of SHP-2 induce hummingbird phenotype
14Conclusion
- 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 CagASHP-2 complex abolished
the CagA-dependent cellular response. - SHP-2 lack membrane-targeting signal sequence
incapable induce cellular morphological change
15Thanks