Protein tyrosine phosphatase a, RPTPa, 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 b (RPTPb) as a VacA-binding protein (Yahiro, K. et al. (1999) J. Biol. Chem. 274, 36693-36699). VacA causes vacuolation of G401 cells, a human kidney tumor cell line, although they do not express RPTPb. 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 RPTPa. The peptide mass fingerprinting of p140 by TOF MS analysis also supported this identification. Treatment of G401 cells with RPTPa-morpholino antisense oligonucleotide before exposure to toxin inhibited vacuolation. These data suggest that RPTPa acts as a receptor for VacA in G401 cells. Thus, two receptor tyrosine phosphatases, RPTPa and RPTPb, serve as VacA receptors.