Pleiotropic actions of Helicobacter pylori vacuolating cytotoxin, VacA

Tohoku Journal of Experimental Medicine

Volumn 220, Issue 1, 2010, Pages 3-14

  Isomoto, Hajime ^a   Moss, Joel ^b   Hirayama, Toshiya ^c  

^a NAGASAKI UNIVERSITY HOSPITAL   (Japan)

^b NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^c NAGASAKI UNIVERSITY   (Japan)

Author keywords

Helicobacter pylori; VacA; Vacuolating toxin

Indexed keywords

GLYCOGEN SYNTHASE KINASE 3BETA; INTERLEUKIN 8; MITOGEN ACTIVATED PROTEIN KINASE P38; PHOSPHATIDYLINOSITOL 3 KINASE; PROSTAGLANDIN E2; PROTEIN BCL 2; RECEPTOR LIKE PROTEIN TYROSINE PHOSPHATASE; RPTPBETA ENZYME; UNCLASSIFIED DRUG; VACUOLATING TOXIN;

ALLELE; APOPTOSIS; BACTERIAL VIRULENCE; CYTOTOXICITY; ENVIRONMENTAL FACTOR; GENE FUNCTION; GENE STRUCTURE; HELICOBACTER PYLORI; HEREDITY; HUMAN; IMMUNOMODULATION; MITOCHONDRIAL MEMBRANE; NONHUMAN; PEPTIC ULCER; PLEIOTROPY; RECEPTOR BINDING; REVIEW; SIGNAL TRANSDUCTION; STOMACH ULCER; T LYMPHOCYTE;

ANIMALS; APOPTOSIS; BACTERIAL PROTEINS; CYTOTOXINS; HELICOBACTER PYLORI; HUMANS; SIGNAL TRANSDUCTION; VACUOLES;

EID: 74949095434     PISSN: 00408727     EISSN: 13493329     Source Type: Journal    
DOI: 10.1620/tjem.220.3     Document Type: Review

References (78)

1. Argent, R.H., Thomas, R.J., Letley, D.P., Rittig, M.G., Hardie, K.R. & Atherton, J.C. (2008) Functional association between the Helicobacter pylori virulence factors VacA and CagA. J. Med. Microbiol., 57, 145-150.
2. Atherton, J.C., Cao, P., Peek, R.M. Jr., Tummuru, M.K., Blaser, M.J. & Cover, T.L. (1995) Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J. Biol. Chem., 270, 17771-17777.
3. Atherton, J.C., Peek, R.M. Jr., Tham, K.T., Cover, T.L. & Blaser, M.J. (1997) Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology, 112, 92-99.
4. Basso, D., Zambon, C.F., Letley, D.P., Stranges, A., Marchet, A., Rhead, J.L., Schiavon, S., Guariso, G., Ceroti, M., Nitti, D., Rugge, M., Plebani, M. & Atherton, J.C. (2008) Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology, 135, 91-99.
5. Blaser, M.J. & Atherton, J.C. (2004) Helicobacter pylori persistence: biology and disease. J. Clin. Invest., 113, 321-333.
6. Boncristiano, M., Paccani, S.R., Barone, S., Ulivieri, C., Patrussi, L., Ilver, D., Amedei, A., D'Elios, M.M., Telford, J.L. & Baldari, C.T. (2003) The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J. Exp. Med., 198, 1887-1897.
7. Covacci, A., Censini, S., Bugnoli, M., Petracca, R., Burroni, D., Macchia, G., Massone, A., Papini, E., Xiang, Z., Figura, N. & Rappuoli, R. (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc. Natl. Acad. Sci. USA, 90, 5791-5795.
8. Cover, T.L. & Blanke, S.R. (2005) Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat. Rev. Microbiol., 3, 320-332.
9. Cover, T.L. & Blaser, M.J. (1992) Purification and characterization of the vacuolating toxin from Helicobacter pylori. J. Biol. Chem., 267, 10570-10575.
10. Cover, T.L., Hanson, P.I. & Heuser, J.E. (1997) Acid-induced dissociation of VacA, the Helicobacter pylori vacuolating cytotoxin, reveals its pattern of assembly. J. Cell Biol., 138, 759-769.
11. Cover, T.L., Reddy, L.Y. & Blaser, M.J. (1993) Effects of ATPase inhibitors on the response of HeLa cells to Helicobacter pylori vacuolating toxin. Infect. Immun., 61, 1427-1431.
12. Czajkowsky, D.M., Iwamoto, H., Cover, T.L. & Shao, Z. (1999) The vacuolating toxin from Helicobacter pylori forms hexameric pores in lipid bilayers at low pH. Proc. Natl. Acad. Sci. USA, 96, 2001-2006.
13. de Bernard, M., Arico, B., Papini, E., Rizzuto, R., Grandi, G., Rappuoli, R. & Montecucco, C. (1997) Helicobacter pylori toxin VacA induces vacuole formation by acting in the cell cytosol. Mol. Microbiol., 26, 665-674.
14. de Guzman, B.B., Hisatsune, J., Nakayama, M., Yahiro, K., Wada, A., Yamasaki, E., Nishi, Y., Yamazaki, S., Azuma, T., Ito, Y., Ohtani, M., van der Wijk, T., den Hertog, J., Moss, J. & Hirayama, T. (2005) Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA. Cell Microbiol., 7, 1285-1293.
15. Deuel, T.F., Zhang, N., Yeh, H.J., Silos-Santiago, I. & Wang, Z.Y. (2002) Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway. Arch. Biochem. Biophys., 397, 162-171.
16. Fujikawa, A., Shirasaka, D., Yamamoto, S., Ota, H., Yahiro, K., Fukada, M., Shintani, T., Wada, A., Aoyama, N., Hirayama, T., Fukamachi, H. & Noda, M. (2003) Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori. Nat. Genet., 33, 375-381.
17. Galmiche, A., Rassow, J., Doye, A., Cagnol, S., Chambard, J.C., Contamin, S., de Thillot, V., Just, I., Ricci, V., Solcia, E., Van Obberghen, E. & Boquet, P. (2000) The N-terminal 34 kDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c release. EMBO J., 19, 6361-6370.
18. Gangwer, K.A., Mushrush, D.J., Stauff, D.L., Spiller, B., McClain, M.S., Cover, T.L. & Lacy, D.B. (2007) Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Proc. Natl. Acad. Sci. USA, 104, 16293-16298.
19. Gauthier, N.C., Monzo, P., Gonzalez, T., Doye, A., Oldani, A., Gounon, P., Ricci, V., Cormont, M. & Boquet, P. (2007) Early endosomes associated with dynamic F-actin structures are required for late trafficking of H. pylori VacA toxin. J. Cell Biol., 177, 343-354.
20. Gauthier, N.C., Monzo, P., Kaddai, V., Doye, A., Ricci, V. & Boquet, P. (2005) Helicobacter pylori VacA cytotoxin: a probe for a clathrin-independent and Cdc42-dependent pinocytic pathway routed to late endosomes. Mol. Biol. Cell, 16, 4852-4866.
21. Gebert, B., Fischer, W., Weiss, E., Hoffmann, R. & Haas, R. (2003) Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science, 301, 1099-1102.
22. Genisset, C., Puhar, A., Calore, F., de Bernard, M., Dell'Antone, P. & Montecucco, C. (2007) The concerted action of the Helicobacter pylori cytotoxin VacA and of the v-ATPase proton pump induces swelling of isolated endosomes. Cell Microbiol., 9, 1481-1490.
23. Hatakeyama, M. (2008) Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA. Oncogene, 27, 7047-7054.
24. Hisatsune, J., Nakayama, M., Isomoto, H., Kurazono, H., Mukaida, N., Mukhopadhyay, A.K., Azuma, T., Yamaoka, Y., Sap, J., Yamasaki, E., Yahiro, K., Moss, J. & Hirayama, T. (2008) Molecular characterization of Helicobacter pylori VacA induction of IL-8 in U937 cells reveals a prominent role for p38MAPK in activating transcription factor-2, cAMP response element binding protein, and NF-kappaB activation. J. Immunol., 180, 5017-5027.
25. 2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells. Infect. Immun., 75, 4472-4481.
26. Hotchin, N.A., Cover, T.L. & Akhtar, N. (2000) Cell vacuolation induced by the VacA cytotoxin of Helicobacter pylori is regulated by the Rac1 GTPase. J. Biol. Chem., 275, 14009-14012.
27. Hussein, NR., Mohammadi, M., Talebkhan, Y., Doraghi, M., Letley, D.P., Muhammad, M.K., Argent, R.H. & Atherton, J.C. (2008) Differences in virulence markers between Helicobacter pylori strains from Iraq and those from Iran: potential importance of regional differences in H. pylori-associated disease. J. Clin. Microbiol., 46, 1774-1779.
28. Isomoto H. (2009) Epigenetic alterations in cholangiocarcinoma-sustained IL-6/STAT3 signaling in cholangio- carcinoma due to SOCS3 epigenetic silencing. Digestion, 79 Suppl 1, 2-8.
29. Ivie, S.E., McClain, M.S., Torres, V.J., Algood, H.M., Lacy, D.B., Yang, R., Blanke, S.R. & Cover, T.L. (2008) Helicobacter pylori VacA subdomain required for intracellular toxin activity and assembly of functional oligomeric complexes. Infect. Immun., 76, 2843-2851.
30. Ji, X., Fernandez, T., Burroni, D., Pagliaccia, C., Atherton, J.C., Reyrat, J.M., Rappuoli, R. & Telford, J.L. (2000) Cell specificity of Helicobacter pylori cytotoxin is determined by a short region in the polymorphic midregion. Infect. Immun., 68, 3754-3757.
31. Kimura, M., Goto, S., Wada, A., Yahiro, K., Niidome, T., Hatakeyama, T., Aoyagi, H., Hirayama, T. & Kondo, T. (1999) Vacuolating cytotoxin purified from Helicobacter pylori causes mitochondrial damage in human gastric cells. Microb. Pathog., 26, 45-52.
32. Kusters, J.G., van Vliet, A.H. & Kuipers, E.J. (2006) Pathogenesis of Helicobacter pylori infection. Clin. Microbiol. Rev., 19, 449-490.
33. Malfertheiner, P., Schultze, V., Rosenkranz, B., Kaufmann, S.H., Ulrichs, T., Novicki, D., Norelli, F., Contorni, M., Peppoloni, S., Berti, D., Tornese, D., Ganju, J., Palla, E., Rappuoli, R., Scharschmidt, B.F. & Del Giudice, G. (2008) Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: a phase I study. Gastroenterology, 135, 787-795.
34. Mashima, H., Suzuki, J., Hirayama, T., Yoshikumi, Y., Ohno, H., Ohnishi, H., Yasuda, H., Fujita, T. & Omata, M. (2008) Involvement of vesicle-associated membrane protein 7 in human gastric epithelial cell vacuolation induced by Helicobacter pylori-produced VacA. Infect. Immun., 76, 2296-2303.
35. McClain, M.S., Iwamoto, H., Cao, P., Vinion-Dubiel, A.D., Li, Y., Szabo, G., Shao, Z. & Cover, T.L. (2003) Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylori vacuolating toxin. J. Biol. Chem., 278, 2101-2108.
36. Menaker, R.J., Ceponis, P.J. & Jones, N.L. (2004) Helicobacter pylori induces apoptosis of macrophages in association with alterations in the mitochondrial pathway. Infect. Immun., 72, 2889-2898.
37. Mérino, D. & Bouillet, P. (2009) The Bcl-2 family in autoimmune and degenerative disorders. Apoptosis, 14, 570-583.
38. Miehlke, S., Yu, J., Schuppler, M., Frings, C., Kirsch, C., Negraszus, N., Morgner, A., Stolte, M., Ehninger, G. & Bayerdörffer, E. (2001) Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease. Am. J. Gastroenterol., 96, 1008-1013.
39. Montecucco, C. & de Bernard, M. (2003) Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori. Microbes. Infect., 5, 715-721.
40. Molinari, M., Galli, C., Norais, N., Telford, J.L., Rappuoli, R., Luzio, J.P. & Montecucco, C. (1997) Vacuoles induced by Helicobacter pylori toxin contain both late endosomal and lysosomal markers. J. Biol. Chem., 272, 25339-25344.
41. Nakayama, M., Hisatsune, J., Yamasaki, E., Nishi, Y., Wada, A., Kurazono, H., Sap, J., Yahiro, K., Moss, J. & Hirayama, T. (2006) Clustering of Helicobacter pylori VacA in lipid rafts, mediated by its receptor, receptor-like protein tyrosine phosphatase beta, is required for intoxication in AZ-521 Cells. Infect. Immun., 74, 6571-6580.
42. Nakayama, M., Kimura, M., Wada, A., Yahiro, K., Ogushi, K., Niidome, T., Fujikawa, A., Shirasaka, D., Aoyama, N., Kurazono, H., Noda, M., Moss, J. & Hirayama, T. (2004) Helicobacter pylori VacA activates the p38/activating transcription factor 2-mediated signal pathway in AZ-521 cells. J. Biol. Chem., 279, 51013-51021.
43. Nakayama, M., Hisatsune, J., Yamasaki, E., Isomoto, H., Kurazono, H., Hatakeyama, M., Azuma, T., Yamaoka, Y., Yahiro, K., Moss, J. & Hirayama, T. (2009) Helicobacter pylori VacA-induced inhibition of GSK3 through the PI3K/Akt signaling pathway. J. Biol. Chem., 284, 1612-1619.
44. Nagy, T.A., Frey, M.R., Yan, F., Israel, D.A., Polk, D.B. & Peek, R.M. Jr. (2009) Helicobacter pylori regulates cellular migration and apoptosis by activation of phosphatidylinositol 3-kinase signaling. J. Infect. Dis., 199, 641-651
45. Oldani, A., Cormont, M., Hofman, V., Chiozzi, V., Oregioni, O., Canonici, A., Sciullo, A., Sommi, P., Fabbri, A., Ricci, V. & Boquet, P. (2009) Helicobacter pylori counteracts the apoptotic action of its VacA toxin by injecting the CagA protein into gastric epithelial cells. PLoS Pathog., 5(10), e1000603.
46. Padilla, P.I., Wada, A., Yahiro, K., Kimura, M., Niidome, T., Aoyagi, H., Kumatori, A., Anami, M., Hayashi, T., Fujisawa, J., Saito, H., Moss, J. & Hirayama, T. (2000) Morphologic differentiation of HL-60 cells is associated with appearance of RPTPbeta and induction of Helicobacter pylori VacA sensitivity. J. Biol. Chem., 275, 15200-15206.
47. Pagliaccia, C., de Bernard, M., Lupetti, P., Ji, X., Burroni, D., Cover, T.L., Papini, E., Rappuoli, R., Telford, J.L. & Reyrat, J.M. (1998) The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc. Natl. Acad. Sci. USA, 95, 10212-10217.
48. Papini, E., Satin, B., Bucci, C., de Bernard, M., Telford, J.L., Manetti, R., Rappuoli, R., Zerial, M. & Montecucco, C. (1997) The small GTP binding protein rab7 is essential for cellular vacuolation induced by Helicobacter pylori cytotoxin. EMBO J., 16, 15-24.
49. Papini, E., Zoratti, M. & Cover, T.L. (2001) In search of the Helicobacter pylori VacA mechanism of action. Toxicon., 39, 1757-1767.
50. Peek, R.M. Jr. & Crabtree, J.E. (2006) Helicobacter pylori infection and gastric neoplasia. J. Pathol., 208, 233-248.
51. Reyrat, J.M., Lanzavecchia, S., Lupetti, P., de Bernard, M., Pagliaccia, C., Pelicic, V., Charrel, M., Ulivieri, C., Norais, N., Ji, X., Cabiaux, V., Papini, E., Rappuoli, R. & Telford, J.L. (1999) 3D imaging of the 58 kDa cell binding subunit of the Helicobacter pylori cytotoxin. J. Mol. Biol., 290, 459-470.
52. Rhead, J.L., Letley, D.P., Mohammadi, M., Hussein, N., Mohagheghi, M.A., Eshagh Hosseini, M. & Atherton, J.C. (2007) A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology, 133, 926-923.
53. Ricci, V., Galmiche, A., Doye, A., Necchi, V., Solcia, E. & Boquet, P. (2000) High cell sensitivity to Helicobacter pylori VacA toxin depends on a GPI-anchored protein and is not blocked by inhibition of the clathrin-mediated pathway of endocytosis. Mol. Biol. Cell., 11, 3897-3909.
54. Roche, N., Ilver, D., Angström, J., Barone, S., Telford, J.L. & Teneberg, S. (2007) Human gastric glycosphingolipids recognized by Helicobacter pylori vacuolating cytotoxin VacA. Microbes. Infect., 9, 605-614.
55. Salama, N.R., Otto, G., Tompkins, L. & Falkow, S. (2001) Vacuolating cytotoxin of Helicobacter pylori plays a role during colonization in a mouse model of infection. Infect. Immun., 69, 730-736.
56. Sewald, X., Fischer, W. & Haas, R. (2008a) Sticky socks: Helicobacter pylori VacA takes shape. Trends Microbiol., 16, 89-92.
57. Sewald, X., Gebert-Vogl, B., Prassl, S., Barwig, I., Weiss, E., Fabbri, M., Osicka, R., Schiemann, M., Busch, D.H., Semmrich, M., Holzmann, B., Sebo, P. & Haas, R. (2008b) Integrin subunit CD18 Is the T-lymphocyte receptor for the Helicobacter pylori vacuolating cytotoxin. Cell. Host. Microbe., 3, 20-29.
58. Shirasaka, D., Aoyama, N., Sakashita, M., Kuroda, K., Maekawa, S., Wambura, C.M., Miyamoto, M., Tamura, T., Yahiro, K., Wada, A., Kurazono, H., Hirayama, T. & Kasuga, M. (2002) Relationship between gastric ulcer and Helicobacter pylori VacA detected in gastric juice using bead-ELISA method. Helicobacter, 7, 281-286.
59. Sokolova, O., Bozko, P.M. & Naumann, M. (2008) Helicobacter pylori suppresses glycogen synthase kinase 3β to promote β-catenin activity. J. Biol. Chem., 283, 29367-29374.
60. Südhof, T.C. & Rothman, J.E. (2009) Membrane fusion: grappling with SNARE and SM proteins. Science, 323, 474-477.
61. Sundrud, M.S., Torres, V.J., Unutmaz, D. & Cover, T.L. (2004) Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc. Natl. Acad. Sci. USA, 101, 7727-7732.
62. Supajatura, V., Ushio, H., Wada, A., Yahiro, K., Okumura, K., Ogawa, H., Hirayama, T. & Ra, C. (2002) Cutting edge: VacA, a vacuolating cytotoxin of Helicobacter pylori, directly activates mast cells for migration and production of proinflammatory cytokines. J. Immunol., 168, 2603-2607.
63. Suzuki, J., Ohnsihi, H., Shibata, H., Wada, A., Hirayama, T., Iiri, T., Ueda, N., Kanamaru, C., Tsuchida, T., Mashima, H., Yasuda, H. & Fujita, T. (2001) Dynamin is involved in human epithelial cell vacuolation caused by the Helicobacter pylori-produced cytotoxin VacA. J. Clin. Invest., 107, 363-370.
64. Suzuki, J., Ohnishi, H., Wada, A., Hirayama, T., Ohno, H., Ueda, N., Yasuda, H., Iiri, T., Wada, Y., Futai, M. & Mashima, H. (2003) Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA. J. Biol. Chem., 278, 25585-25590.
65. Tabassam, F.H., Graham, D.Y. & Yamaoka, Y. (2009) Helicobacter pylori activate epidermal growth factor receptor- and phosphatidylinositol 3-OH kinase-dependent Akt and glycogen synthase kinase 3beta phosphorylation. Cell Microbiol., 11, 70-82.
66. Tegtmeyer, N., Zabler, D., Schmidt, D., Hartig, R., Brandt, S. & Backert, S. (2009) Importance of EGF receptor, HER2/Neu and Erk1/2 kinase signalling for host cell elongation and scattering induced by the Helicobacter pylori CagA protein: antagonistic effects of the vacuolating cytotoxin VacA. Cell Microbiol., 11, 488-505.
67. Telford, J.L., Ghiara, P, Dell'Orco, M., Comanducci, M., Burroni, D., Bugnoli, M., Tecce, M.F., Censini, S., Covacci, A., Xiang, Z., Papini, E., Montecucco, C., Parente L. & Rappuoli, R. (1994) Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease. J. Exp. Med., 179, 1653-1658
68. Tombola, F., Carlesso, C., Szabò, I., de Bernard, M., Reyrat, J.M., Telford, J.L., Rappuoli, R., Montecucco, C., Papini, E. & Zoratti, M. (1999) Helicobacter pylori vacuolating toxin forms anion-selective channels in planar lipid bilayers: possible implications for the mechanism of cellular vacuolation. Biophys. J., 76, 1401-1409.
69. Torres, V.J., Van Compernolle, S.E., Sundrud, M.S., Unutmaz, D. & Cover, T.L. (2007) Helicobacter pylori vacuolating cytotoxin inhibits activation-induced proliferation of human T and B lymphocyte subsets. J. Immunol., 179, 5433-5440.
70. Tuo, B., Song, P., Wen, G., Sewald, X., Gebert-Vogl, B., Haas, R., Manns, M. & Seidler, U. (2009) Helicobacter pylori vacuolating cytotoxin inhibits duodenal bicarbonate secretion by a histaminedependent mechanism in mice. J. Infect. Dis., 199, 505-512.
71. van Doorn, L.J., Figueiredo, C., Mégraud, F., Pena, S., Midolo, P., Queiroz, D.M., Carneiro, F., Vanderborght, B., Pegado, M.D., Sanna, R., De Boer, W., Schneeberger, P.M., Correa, P., Ng, E.K., Atherton, J., Blaser, M.J. & Quint, W.G. (1999) Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology, 16, 823-830.
72. Wang, F., Xia, P., Wu, F., Wang, D., Wang, W., Ward, T., Liu, Y., Aikhionbare, F., Guo, Z., Powell, M., Liu, B., Bi, F., Shaw, A., Zhu, Z., Elmoselhi, A., Fan, D., Cover, T.L., Ding, X. & Yao, X. (2008) Helicobacter pylori VacA disrupts apicalmembrane-cytoskeletal interactions in gastric parietal cells. J. Biol. Chem., 283, 26714-26725.
73. Wen, S. & Moss, S.F. (2009) Helicobacter pylori virulence factors in gastric carcinogenesis. Cancer Lett., 282, 1-8.
74. Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K., Wada, A., Moss, J. & Hirayama, T. (1999) Activation of Helicobacter pylori VacA toxin by alkaline or acid conditions increases its binding to a 250-kDa receptor protein-tyrosine phosphatase beta. J. Biol. Chem., 274, 36693-36699.
75. Yahiro, K., Wada, A., Nakayama, M., Kimura, T., Ogushi, K., Niidome, T., Aoyagi, H., Yoshino, K., Yonezawa, K., Moss, J. & Hirayama, T. (2003) Protein-tyrosine phosphatase alpha, RPTP alpha, is a Helicobacter pylori VacA receptor. J. Biol. Chem., 278, 19183-19189.
76. Yahiro, K., Wada, A., Yamasaki, E., Nakayama, M., Nishi, Y., Hisatsune, J., Morinaga, N., Sap, J., Noda, M., Moss, J. & Hirayama, T. (2004) Essential domain of receptor tyrosine phosphatase β (RPTPβ) for interaction with Helicobacter pylori vacuolating cytotoxin. J. Biol. Chem., 279, 1013-1021.
77. Yamasaki, E., Wada, A., Kumatori, A., Nakagawa, I., Funao, J., Nakayama, M., Hisatsune, J., Kimura, M., Moss, J. & Hirayama, T. (2006) Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome c release and cell death, independent of vacuolation. J. Biol. Chem., 281, 11250-11259.
78. Yokoyama, K., Higashi, H., Ishikawa, S., Fujii, Y., Kondo, S., Kato, H., Azuma, T., Wada, A., Hirayama, T., Aburatani, H. & Hatakeyama, M. (2005) Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. Proc. Natl. Acad. Sci. USA, 102, 9661-9666.