Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA

• Published in: Cellular microbiology Vol. 7; no. 9; pp. 1285 - 1293
• Main Authors: De Guzman, Blanquita B, Hisatsune, Junzo, Nakayama, Masaaki, Yahiro, Kinnosuke, Wada, Akihiro, Yamasaki, Eiki, Nishi, Yoshito, Yamazaki, Shiho, Azuma, Takeshi, Ito, Yoshiyuki, Ohtani, Masahiro, van der Wijk, Thea, den Hertog, Jeroen, Moss, Joel, Hirayama, Toshiya
• Format: Journal Article
• Language: English
• Published: England 01.09.2005
• Subjects: Adenocarcinoma; Bacterial Adhesion; Bacterial Proteins - metabolism; Bacterial Proteins - pharmacology; Cell Line, Tumor; HeLa Cells; Helicobacter pylori - metabolism; Humans; Hydrogen-Ion Concentration; Immunoprecipitation; Nerve Tissue Proteins - metabolism; Protein Isoforms - metabolism; Protein Processing, Post-Translational; Protein Tyrosine Phosphatases - metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 4; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Receptors, Cell Surface - metabolism; Stomach Neoplasms; Vacuoles - drug effects; Vacuoles - ultrastructure
• ISSN: 1462-5814

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.