Helicobacter pylori VacA, acting through receptor protein tyrosine phosphatase α, is crucial for CagA phosphorylation in human duodenum carcinoma cell line AZ-521

Masayuki Nakano, Kinnosuke Yahiro, Eiki Yamasaki, Hisao Kurazono, Junko Akada, Yoshio Yamaoka, Takuro Niidome, Masanori Hatakeyama, Hidekazu Suzuki, Taro Yamamoto, Joel Moss, Hajime Isomoto, Toshiya Hirayama

研究成果: Article

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Helicobacter pylori, a major cause of gastroduodenal diseases, produces vacuolating cytotoxin (VacA) and cytotoxin-associated gene A (CagA), which seem to be involved in virulence. VacA exhibits pleiotropic actions in gastroduodenal disorders via its specific receptors. Recently, we found that VacA induced the phosphorylation of cellular Src kinase (Src) at Tyr418 in AZ-521 cells. Silencing of receptor protein tyrosine phosphatase (RPTP)α, a VacA receptor, reduced VacA-induced Src phosphorylation. Src is responsible for tyrosine phosphorylation of CagA at its Glu-Pro-Ile-Tyr-Ala (EPIYA) variant C (EPIYA-C) motif in Helicobacter pylori-infected gastric epithelial cells, resulting in binding of CagA to SHP-2 phosphatase. Challenging AZ-521 cells with wild-type H. pylori induced phosphorylation of CagA, but this did not occur when challenged with a vacA gene-disrupted mutant strain. CagA phosphorylation was observed in cells infected with a vacA gene-disrupted mutant strain after addition of purified VacA, suggesting that VacA is required for H. pylori-induced CagA phosphorylation. Following siRNA-mediated RPTPα knockdown in AZ-521 cells, infection with wild-type H. pylori and treatment with VacA did not induce CagA phosphorylation. Taken together, these results support our conclusion that VacA mediates CagA phosphorylation through RPTPα in AZ-521 cells. These data indicate the possibility that Src phosphorylation induced by VacA is mediated through RPTPα, resulting in activation of Src, leading to CagA phosphorylation at Tyr972 in AZ-521 cells.

元の言語English
ページ(範囲)1473-1481
ページ数9
ジャーナルDMM Disease Models and Mechanisms
9
発行部数12
DOI
出版物ステータスPublished - 2016 12 1

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Nakano, M., Yahiro, K., Yamasaki, E., Kurazono, H., Akada, J., Yamaoka, Y., Niidome, T., Hatakeyama, M., Suzuki, H., Yamamoto, T., Moss, J., Isomoto, H., & Hirayama, T. (2016). Helicobacter pylori VacA, acting through receptor protein tyrosine phosphatase α, is crucial for CagA phosphorylation in human duodenum carcinoma cell line AZ-521. DMM Disease Models and Mechanisms, 9(12), 1473-1481. https://doi.org/10.1242/dmm.025361