Protein-tyrosine phosphatase α, RPTPα, is a Helicobacter pylori VacA receptor

Kinnosuke Yahiro, Akihiro Wada, Masaaki Nakayama, Takahiro Kimura, Ken ichi Ogushi, Takuro Niidome, Haruhiko Aoyagi, Ken ichi Yoshino, Kazuyoshi Yonezawa, Joel Moss, Toshiya Hirayama

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99 Citations (Scopus)

Abstract

Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation, mitochondrial damage, cytochrome c release, and apoptosis of gastric epithelial cells. To detect gastric proteins that serve as VacA receptors, we used VacA co-immunoprecipitation techniques following biotinylation of the cell surface and identified p250, a receptor-like protein-tyrosine phosphatase β (RPTPβ) as a VacA-binding protein (Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K., Wada, A., Moss, J., and Hirayama, T. (1999) J. Biol. Chem. 274, 36693-36699). VacA causes vacuolation of G401 cells, a human kidney tumor cell line, although they do not express RPTPβ. By co-immunoprecipitation with VacA, we identified p140 as a potential receptor in those cells. p140 purified by chromatography on a peanut agglutinin affinity matrix contained internal amino acid sequences of RGEENTDYVNASFIDGYRQK and AEGILDVFQTVK, which are identical to those in RPTPα. The peptide mass fingerprinting of p140 by time of flight-MS analysis also supported this identification. Treatment of G401 cells with RPTPα-morpholino antisense oligonucleotide before exposure to toxin inhibited vacuolation. These data suggest that RPTPα acts as a receptor for VacA in G401 cells. Thus, two receptor tyrosine phosphatases, RPTPα and RPTPβ, serve as VacA receptors.

Original languageEnglish
Pages (from-to)19183-19189
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number21
DOIs
Publication statusPublished - May 23 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yahiro, K., Wada, A., Nakayama, M., Kimura, T., Ogushi, K. I., Niidome, T., Aoyagi, H., Yoshino, K. I., Yonezawa, K., Moss, J., & Hirayama, T. (2003). Protein-tyrosine phosphatase α, RPTPα, is a Helicobacter pylori VacA receptor. Journal of Biological Chemistry, 278(21), 19183-19189. https://doi.org/10.1074/jbc.M300117200