Abstract |
Helicobacter pylori CagA protein is associated with severe gastritis and gastric carcinoma. CagA is injected from the attached Helicobacter pylori into host cells and undergoes tyrosine phosphorylation. Wild-type but not phosphorylation-resistant CagA induced a growth factor-like response in gastric epithelial cells. Furthermore, CagA formed a physical complex with the SRC homology 2 domain (SH2)-containing tyrosine phosphatase SHP-2 in a phosphorylation-dependent manner and stimulated the phosphatase activity. Disruption of the CagA-SHP-2 complex abolished the CagA-dependent cellular response. Conversely, the CagA effect on cells was reproduced by constitutively active SHP-2. Thus, upon translocation, CagA perturbs cellular functions by deregulating SHP-2.
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Authors | Hideaki Higashi, Ryouhei Tsutsumi, Syuichi Muto, Toshiro Sugiyama, Takeshi Azuma, Masahiro Asaka, Masanori Hatakeyama |
Journal | Science (New York, N.Y.)
(Science)
Vol. 295
Issue 5555
Pg. 683-6
(Jan 25 2002)
ISSN: 1095-9203 [Electronic] United States |
PMID | 11743164
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Bacterial
- Bacterial Proteins
- Dipeptides
- Enzyme Inhibitors
- Intracellular Signaling Peptides and Proteins
- Recombinant Fusion Proteins
- cagA protein, Helicobacter pylori
- calpeptin
- Phosphotyrosine
- PTPN11 protein, human
- PTPN6 protein, human
- Protein Tyrosine Phosphatase, Non-Receptor Type 11
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
- Protein Tyrosine Phosphatases
- SH2 Domain-Containing Protein Tyrosine Phosphatases
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Topics |
- Amino Acid Substitution
- Animals
- Antigens, Bacterial
- Bacterial Proteins
(genetics, metabolism)
- COS Cells
- Cell Membrane
(enzymology, metabolism)
- Cell Size
- Dipeptides
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Gastric Mucosa
(cytology, enzymology)
- Helicobacter pylori
(genetics, pathogenicity)
- Humans
- Intracellular Signaling Peptides and Proteins
- Mutation
- Phenotype
- Phosphorylation
- Phosphotyrosine
(metabolism)
- Protein Tyrosine Phosphatase, Non-Receptor Type 11
- Protein Tyrosine Phosphatase, Non-Receptor Type 6
- Protein Tyrosine Phosphatases
(antagonists & inhibitors, chemistry, genetics, metabolism)
- Recombinant Fusion Proteins
(metabolism)
- SH2 Domain-Containing Protein Tyrosine Phosphatases
- Transfection
- Virulence
- src Homology Domains
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