Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTP[alpha] and RPTP[beta], by Helicobacter pylori m2VacA

• Published in: Cellular microbiology Vol. 7; no. 9; p. 1285
• 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: Oxford Hindawi Limited 01.09.2005
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2005.00556.x

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, RPTPα and RPTPβ suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTPα, not RPTPβ, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTPα, not RPTPβ, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPα of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTPα less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTPα 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 RPTPα in HeLa cells may be responsible for the reduced susceptibility to m2VacA.