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
Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 8528523, Japan.
Cell Microbiol. 2005 Sep;7(9):1285-93. 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, 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.
幽门螺杆菌空泡毒素VacA可诱导哺乳动物细胞系出现空泡化。VacA分子中部的序列差异界定了两个家族，即m1VacA和m2VacA，它们在细胞特异性方面存在差异。与m1VacA相似，m2VacA可被酸或碱激活，这增强了其与细胞的结合能力。免疫沉淀实验表明，在AZ - 521细胞中，激活后的m2VacA与m1VacA类似，可与两种受体样蛋白酪氨酸磷酸酶RPTPα和RPTPβ结合，这表明激活后的m2VacA以及m1VacA可能在幽门螺杆菌感染后导致胃肠道疾病。G401细胞表达RPTPα，不表达RPTPβ，且对m1VacA和m2VacA均有反应。HeLa细胞同样表达RPTPα，不表达RPTPβ，但与其他细胞系不同的是，其对m2VacA反应较差。m1VacA与HeLa细胞的RPTPα结合程度与其他毒素敏感细胞相似，而激活后的m2VacA与HeLa细胞RPTPα的结合较差，这与其对这些细胞的低空泡化活性一致。HeLa细胞中RPTPα的分子量小于G401细胞中的该蛋白，尽管它们的细胞外氨基酸序列几乎相同，仅发现两个氨基酸差异。HeLa细胞中RPTPα不同的翻译后修饰可能是其对m2VacA敏感性降低的原因。
