title: Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA.
abstract: Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian cell lines. Sequence differences in the middle of VacA molecules define two families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTPalpha, not RPTPbeta, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTPalpha, not RPTPbeta, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPalpha of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTPalpha less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTPalpha from HeLa cells is less than that of the protein from G401 cells, although their extracellular amino acid sequences are virtually identical, with only two amino acid differences noted. Different post-translational modifications of RPTPalpha in HeLa cells may be responsible for the reduced susceptibility to m2VacA.
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 8528523, Japan.
authors.forename: Blanquita B
authors.initials: BB
authors.lastname: De Guzman
authors.forename: Junzo
authors.initials: J
authors.lastname: Hisatsune
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakayama
authors.forename: Kinnosuke
authors.initials: K
authors.lastname: Yahiro
authors.forename: Akihiro
authors.initials: A
authors.lastname: Wada
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamasaki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nishi
authors.forename: Shiho
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohtani
authors.forename: Thea
authors.initials: T
authors.lastname: van der Wijk
authors.forename: Jeroen
authors.initials: J
authors.lastname: den Hertog
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.forename: Toshiya
authors.initials: T
authors.lastname: Hirayama
mesh_terms: D000230:Adenocarcinoma; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D047468:Immunoprecipitation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013274:Stomach Neoplasms; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure*
chemical_list: D001426:Bacterial Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; C074689:VacA protein, Helicobacter pylori; C516841:PTPRA protein, human; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5