Activation of Helicobacter pylori VacA toxin by alkaline or acid conditions increases its binding to a 250-kDa receptor protein-tyrosine phosphatase β

Kinnosuke Yahiro, Takuro Niidome, Miyuki Kimura, Tomomitsu Hatakeyama, Haruhiko Aoyagi, Hisao Kurazono, Ken Ichi Imagawa, Akihiro Wada, Joel Moss, Toshiya Hirayama

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139 Citations (Scopus)

Abstract

Helicobacter pylori, a Gram-negative gastric bacterium, secretes VacA, a cytotoxin that causes vacuolar degeneration of susceptible cells. Velocity sedimentation analysis showed that treatment of VacA at alkaline pH led to disassembly of VacA oligomers, an observation reported previously for acid- treated VacA. Exposure of VacA to acid or alkali increased its binding to AZ- 521 cells, as shown by indirect immunofluorescence and flow cytometry. Moreover, immunoprecipitates with polyclonal antibodies against VacA from AZ- 521 cells previously exposed to acid- or alkali-treated VacA had a 250-kDa glycoprotein containing galactose-β(1-3)-N-acetylgalactosamine and galactose-β(1-4)-N-acetylglucosamine. p250, purified by chromatography on peanut agglutinin affinity and Superose 6 columns, contained N-terminal and internal amino acid sequences of YRQQRKLVEEIGWSYT and LIIQDHILEATQDDY, respectively. These sequences are identical to those of a receptor protein- tyrosine phosphatase (RPTPβ/PTPζ); in agreement, p250 reacted with anti- human RPTPβ monoclonal antibody. Immunopreeipitation with antihuman RPTPβ antibody of solubilized membrane preparations previously incubated with VacA or heat-inactivated VacA demonstrated that RPTPβ bound native, but not denatured, VacA. Acidic and alkaline treatments were associated with activation of VacA and increased binding to the cell surface RPTPβ.

Original languageEnglish
Pages (from-to)36693-36699
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number51
DOIs
Publication statusPublished - Dec 17 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K. I., Wada, A., Moss, J., & Hirayama, T. (1999). Activation of Helicobacter pylori VacA toxin by alkaline or acid conditions increases its binding to a 250-kDa receptor protein-tyrosine phosphatase β. Journal of Biological Chemistry, 274(51), 36693-36699. https://doi.org/10.1074/jbc.274.51.36693