[en] A key virulence factor for Yersinia pestis, the etiologic agent of plague, is the tyrosine phosphatase YopH, which the bacterium injects into host cells. We report that treatment of human T lymphocytes with a recombinant membrane-permeable YopH resulted in severe reduction in intracellular tyrosine phosphorylation and inhibition of T cell activation. The primary signal transducer for the T cell antigen receptor, the Lck tyrosine kinase, was specifically precipitated by a substrate-trapping YopH mutant, and Lck was dephosphorylated at its positive regulatory site, Tyr-394, in cells containing active YopH. By turning off Lck, YopH blocks T cell antigen receptor signaling at its very first step, effectively preventing the development of a protective immune response against this lethal bacterium.
Titball, R. W., and Leary, S. E. (1998) Br. Med. Bull. 54, 625-633
Hinnebusch, B. J. (1997) J. Mol. Med. 75, 645-652
Christie, A. B. (1982) Ecol. Dis. 1, 111-115
Cleri, D. J., Vernaleo, J. R., Lombardi, L. J., Rabbat, M. S., Mathew, A., Marton, R., and Reyelt, M. C. (1997) Semin. Resp. Infect. 12, 12-23
Titball, R. W., and Williamson, E. D. (2001) Vaccine 19, 4175-4184
Friedlander, A. M., Welkos, S. L., Worsham, P. L., Andrews, G. P., Heath, D. G., Anderson, G. W. Jr., Pitt, M. L., Estep, J., and Davis, K. (1995) Clin. Infect. Dis. 21, Suppl. 2, 178-181
Inglesby, T. V., Dennis, D. T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Fine, A. D., Friedlander, A. M., Hauer, J., Koerner, J. F., Layton, M., McDade, J., Osterholm, M. T., O'Toole, T., Parker, G., Perl, T. M., Russell, P. K., Schoch-Spana, M., and Tonat, K. (2000) JAMA 283, 2281-2290
Cornelis, G. R., Boland, A., Boyd, A. P., Geuijen, C., Iriarte, M., Neyt, C., Sory, M. P., and Stainier, I. (1998) Microbiol. Mol. Biol. Rev. 62, 1315-1352
Cornelis, G. R., and Wolf-Watz, H. (1997) Mol. Microbiol. 23, 861-867
Cornelis, G. R. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 8778-8783
Cheng, L. W., and Schneewind, O. (2000) (2000) J. Bacteriol. 182, 3183-3190
Persson, C., Nordfelth, R., Holmstrom, A., Hakansson, S., Rosqvist, R., and Wolf-Watz, H. (1995) Mol. Microbiol. 18, 135-150
Guan, K., and Dixon, J. E. (1990) Science 249, 553-556
Bliska, J. B., Guan, K., Dixon, J. E., and Falkow, S. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 1187-1191
Montagna, L. G., Ivanov, M. I., and Bliska, J. B. (2001) J. Biol. Chem. 276, 5005-5011
Evdokimov, A. G., Tropea, J. E., Routzahn, K. M., Copeland, T. D., and Waugh, D. S. (2001) Acta Cryst. 57, 793-799
Stuckey, J. A., Schubert, H. L., Fauman, E. B., Zhang, Z. Y., and Dixon, J. E. (1994) Nature 370, 571-575
Black, D. S., and Bliska, J. B. (1997) EMBO J. 16, 2730-2744
Persson, C., Carballeira, N., Wolf-Watz, H., and Fallman, M. (1997) EMBO J. 16, 2307-2318
Andersson, K., Carballeira, N., Magnusson, K. E., Persson, C., Stendahl, O., Wolf-Watz, H., and Fallman, M. (1996) Mol. Microbiol. 20, 1057-1069
Ernst, J. D. (2000) Cell. Microbiol. 2, 379-386
Aepfelbacher, M., Zumbihl, R., Ruckdeschel, K., Jacobi, C. A., Barz, C., and Heesemann, J. (1999) Biol. Chem. 380, 795-802
Green, S. P., Hartland, E. L., Robins-Browne, R. M., and Phillips, W. A. (1995) J. Leukocyte Biol. 57, 972-977
Yao, T., Mecsas, J., Healy, J. I., Falkow, S., and Chien, Y. (1999) J. Exp. Med. 190, 1343-1350
Kholod, N., and Mustelin, T. (2001) BioTechniques 31, 322-328
Couture, C., Baier, G., Oetken, C., Williams, S., Telford, D., Marie-Cardine, A., Baier-Bitterlich, G., Fischer, S., Burn, P., Altman, A., and Mustelin, T. (1994) Mol. Cell. Biol. 14, 5249-5258
Wang, X., Huynh, H., Gjörloff-Wingren, A., Monosov, E., Stridsberg, M., Fukuda, M., and Mustelin, T. (2002) J. Immunol. 168, 4612-4619
Saxena, M., Williams, S., Taskén, K., and Mustelin, T. (1999) Nat. Cell Biol. 1, 305-311
Alonso, A., Saxena, M., Williams, S., and Mustelin, T. (2001) J. Biol. Chem. 276, 4766-4771
Alonso, A., Rahmouni, S., Williams, S., van Stipdonk, M., Jaroszewski, L., Godzik, A., Abraham, R. T., Schoenberger, S., and Mustelin, T. (2003) Nat. Immunol. 4, 44-48
Gjörloff-Wingren, A., Saxena, M., Han, S., Wang, X., Alonso, A., Renedo, M., Oh, P., Williams, S., Schnitzer, J., and Mustelin, T. (2000) Eur. J. Immunol. 30, 2412-2421
Wadia, J. S., and Dowdy, S. F. (2002) Curr. Opin. Biotech. 13, 52-58
Flint, A. J., Tiganis, T., Barford, D., and Tonks, N. K. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 1680-1685
Mustelin, T., Abraham, R. T., Rudd, C. E., Alonso, A., and Merlo, J. J. (2002) Front. Biosci. 7, 918-969
Mustelin, T. (1994) Src Family Tyrosine Kinases in Leukocytes, R. G. Landes Co., Austin, TX