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Helicobacter pylori CagA protein is
associated with severe gastritis and gastric carcinoma. CagA is
injected from the attachedHelicobacter pylori into host
cells and undergoes tyrosine phosphorylation.Wild-type but
not phosphorylation-resistant CagA induced a growthfactor-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-dependentmanner and stimulated the
phosphatase activity. Disruption ofthe CagA-SHP-2 complex
abolished the CagA-dependent cellular response.Conversely, the CagA
effect on cells was reproduced by constitutivelyactive SHP-2. Thus,
upon translocation, CagA perturbs cellularfunctions by deregulating
SHP-2.
1 Division of Molecular Oncology, Institute for
Genetic Medicine and Graduate School of Science, Hokkaido University,
Sapporo 060-0815, Japan.
2 Department of
Gastroenterology & Hematology, Graduate School of Medicine, Hokkaido
University, Sapporo 060-0815, Japan.
3 The Second
Department of Internal Medicine, Fukui Medical University, Fukui
910-1193, Japan.
*
To whom correspondence should be addressed. E-mail:
mhata{at}imm.hokudai.ac.jp
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278, 4821-4825
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Attenuation of Helicobacter pylori CagA{middle dot}SHP-2 Signaling by Interaction between CagA and C-terminal Src Kinase.
R. Tsutsumi, H. Higashi, M. Higuchi, M. Okada, and M. Hatakeyama (2003)
J. Biol. Chem.
278, 3664-3670
|Abstract »|Full Text »|PDF »
Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection.
K. Guillemin, N. R. Salama, L. S. Tompkins, and S. Falkow (2002)
PNAS
99, 15136-15141
|Abstract »|Full Text »|PDF »
Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites.
H. Higashi, R. Tsutsumi, A. Fujita, S. Yamazaki, M. Asaka, T. Azuma, and M. Hatakeyama (2002)
PNAS
99, 14428-14433
|Abstract »|Full Text »|PDF »
Helicobacter pylori Infection.
S. Suerbaum and P. Michetti (2002)
N. Engl. J. Med.
347, 1175-1186
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cag+Helicobacter pylori Induces Homotypic Aggregation of Macrophage-Like Cells by Up-Regulation and Recruitment of Intracellular Adhesion Molecule 1 to the Cell Surface.
S. Moese, M. Selbach, T. F. Meyer, and S. Backert (2002)
Infect. Immun.
70, 4687-4691
|Abstract »|Full Text »|PDF »
Gastric Cancers Overexpress DARPP-32 and a Novel Isoform, t-DARPP.
W.'e. El-Rifai, M. F. Smith Jr., G. Li, A. Beckler, V. S. Carl, E. Montgomery, S. Knuutila, C. A. Moskaluk, H. F. Frierson Jr., and S. M. Powell (2002)
Cancer Res.
62, 4061-4064
|Abstract »|Full Text »|PDF »
