Deregulation of SHP-2 tyrosine phosphatase by the Helicobacter pylori virulence factor CagA
スポンサーリンク
概要
- 論文の詳細を見る
Helicobacter pylori (H. pylori) is estimated to infect about half of the world population. It causes gastric diseases ranging from gastritis to cancer and has been classified as a class I carcinogen by WHO. However, little is known about the molecular mechanisms by which H. pylori induces pathogenesis. CagA is the product of the cagA gene carried among virulent H. pylori strains and is associated with severe clinical outcomes, most notably gastric carcinoma. CagA is injected from the attached H. pylori into gastric epithelial cells and undergoes tyrosine phosphorylation. We found that wild-type, but not phosphorylation-resistant CagA, is capable of inducing a growth factor-like morphological change, termed the hummingbird phenotype, in cells. Furthermore, CagA specifically binds the SH2-containing protein tyrosine phosphatase SHP-2 in a tyrosine phosphorylation-dependent manner and stimulates phosphatase activity. Disruption of the CagA-SHP-2 complex abolishes the CagA-dependent morphological change. Conversely, constitutively active SHP-2 is capable of inducing a CagA-like morphological change when it is plasma membrane-targeted. Our results show that CagA perturbs cellular functions by deregulating SHP-2 phosphatase after translocation from H. pylori into gastric epithelial cells. Given the positive regulatory roles of SHP-2 in both cell proliferation and cell movement, the CagA-SHP-2 interaction may play an important role in the oncogenic transformation that is a hallmark of cagA+ H. pylori infection.
- The Keio Journal of Medicineの論文
- 2002-12-01
著者
-
Hatakeyama Masanori
Division Of Molecular Oncology Institute For Genetic Medicine And Division Of Chemistry Graduate Sch
-
Hatakeyama Masanori
Division Of Molecular Oncology Institute For Genetic Medicine And Graduate School Of Science Hokkaid
関連論文
- Structural and functional diversity in the PAR1b/MARK2-binding region of Helicobacter pylori CagA
- Conditional gene silencing utilizing the lac repressor reveals a role of SHP-2 in cagA-positive Helicobacter pylori pathogenicity
- O-ADP-Ribosylation in the NAD/NADase System : 2-Alkanols as Efficient Substrates
- Helicobacter pylori CagA : a new paradigm for bacterial carcinogenesis
- Deregulation of SHP-2 tyrosine phosphatase by the Helicobacter pylori virulence factor CagA
- Helicobacter pylori and gastric carcinogenesis
- Unusual Enzymatic Hydrolysis of NAD by Solubilized Form of NAD^+ Glycohydrolase