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SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein
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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Cited by
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Kusters, J. G., van Vliet, A. H. M., & Kuipers, E. J. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.00054-05 · Cited by 2,526
The ‘Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling
Neel, B. G., Gu, H., & Pao, L. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00091-4 · Cited by 1,249
Helicobacter pylori: gastric cancer and beyond
Polk, D. B., & Peek, R. M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2857 · Cited by 1,158
Functional and quantitative proteomics using SILAC
Mann, M. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2067 · Cited by 931
Pathogenicity Islands in BacterialPathogenesis
Schmidt, H., & Hensel, M. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.1.14-56.2004 · Cited by 776
Metadata
- Authors
- Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., & Hatakeyama, M.
- Venue
- Science
- Published
- 2002-01-25
- Volume
- 295
- Issue
- 5555
- Pages
- 683-686
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2090681869
- Cited by
- 1,029
- References
- 0
- FWCI
- 65.64
- Type
- journal article
- Language
- en
- Open access
- closed
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- Higashi, H., Tsutsumi, R., Muto, S., Sugiyama, T., Azuma, T., Asaka, M., & Hatakeyama, M. (2002). SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter pylori CagA Protein. Science. https://doi.org/10.1126/science.1067147
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