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

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 beta (RPTPbeta) 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 RPTPbeta. 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 RPTPalpha. The peptide mass fingerprinting of p140 by time of flight-MS analysis also supported this identification. Treatment of G401 cells with RPTPalpha-morpholino antisense oligonucleotide before exposure to toxin inhibited vacuolation. These data suggest that RPTPbeta acts as a receptor for VacA in G401 cells. Thus, two receptor tyrosine phosphatases, RPTPalpha and RPTPbeta, serve as VacA receptors.