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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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Helicobacter pylori Arginase Inhibits T Cell Proliferation and Reduces the Expression of the TCR {zeta}-Chain (CD3{zeta}).
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Helicobacter pylori Induces AGS Cell Motility and Elongation via Independent Signaling Pathways.
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72, 3646-3649
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Distinct Diversity of the cag Pathogenicity Island among Helicobacter pylori Strains in Japan.
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42, 2508-2517
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Helicobacter pylori CagA Induces Ras-independent Morphogenetic Response through SHP-2 Recruitment and Activation.
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Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer.
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Plasticity of Repetitive DNA Sequences within a Bacterial (Type IV) Secretion System Component.
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Correlation between cag Pathogenicity Island Composition and Helicobacter pylori-Associated Gastroduodenal Disease.
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Proteolysis of Enteric Cell Villin by Entamoeba histolytica Cysteine Proteinases.
T. Lauwaet, M. J. Oliveira, B. Callewaert, G. De Bruyne, X. Saelens, S. Ankri, P. Vandenabeele, D. Mirelman, M. Mareel, and A. Leroy (2003)
J. Biol. Chem.
278, 22650-22656
|Abstract »|Full Text »|PDF »
Effects of Helicobacter pylori on intracellular Ca2+ signaling in normal human gastric mucous epithelial cells.
K. L. Marlink, K. D. Bacon, B. C. Sheppard, H. Ashktorab, D. T. Smoot, T. L. Cover, C. W. Deveney, and M. J. Rutten (2003)
Am J Physiol Gastrointest Liver Physiol
285, G163-G176
|Abstract »|Full Text »|PDF »
pH-Regulated Gene Expression of the Gastric Pathogen Helicobacter pylori.
D. S. Merrell, M. L. Goodrich, G. Otto, L. S. Tompkins, and S. Falkow (2003)
Infect. Immun.
71, 3529-3539
|Abstract »|Full Text »|PDF »
Disruption of the Epithelial Apical-Junctional Complex by Helicobacter pylori CagA.
M. R. Amieva, R. Vogelmann, A. Covacci, L. S. Tompkins, W. J. Nelson, and S. Falkow (2003)
Science
300, 1430-1434
|Abstract »|Full Text »|PDF »
Distinctive Patterns of Gene Expression in Premalignant Gastric Mucosa and Gastric Cancer.
A. Boussioutas, H. Li, J. Liu, P. Waring, S. Lade, A. J. Holloway, D. Taupin, K. Gorringe, I. Haviv, P. V. Desmond, et al. (2003)
Cancer Res.
63, 2569-2577
|Abstract »|Full Text »|PDF »
Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response.
Y. Churin, L. Al-Ghoul, O. Kepp, T. F. Meyer, W. Birchmeier, and M. Naumann (2003)
J. Cell Biol.
161, 249-255
|Abstract »|Full Text »|PDF »
Clinical, Cellular, and Molecular Aspects of Cancer Invasion.
The impact of parietal cells on Helicobacter pylori tropism and host pathology: An analysis using gnotobiotic normal and transgenic mice.
A. J. Syder, J. D. Oh, J. L. Guruge, D. O'Donnell, M. Karlsson, J. C. Mills, B. M. Bjorkholm, and J. I. Gordon (2003)
PNAS
100, 3467-3472
|Abstract »|Full Text »|PDF »
Up-regulated Smad5 Mediates Apoptosis of Gastric Epithelial Cells Induced by Helicobacter pylori Infection.
T. Nagasako, T. Sugiyama, T. Mizushima, Y. Miura, M. Kato, and M. Asaka (2003)
J. Biol. Chem.
278, 4821-4825
|Abstract »|Full Text »|PDF »
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 »
