Abstract
STIMULATION of T lymphocytes through their antigen receptor (T-cell receptor; TCR) results in the activation of a tyrosine kinase1,2 and the generation of phosphatidyl inositol (PtdIns)-derived second messengers3–5. Several reports have indicated that CD45, a haematopoetic cell-specific surface glycoprotein with tyrosine phosphatase activity in its cytoplasmic domain6–10, is important in lymphocyte activation11–14. To examine the possibility that CD45 might influence proximal signal transduction events through the TCR, we have isolated a variant of the human T-cell leukaemic line, HPB-ALL, which fails to express this phosphatase. Unlike cells expressing CD45, stimulation of the TCR in the CD45-negative cell does not result in PtdIns-derived second messengers. Reconstitution of CD45 expression restored early signalling events through the TCR. To localize the site of CD45 action, the human muscarinic type 1 receptor, which also activates the Ptdlns second messenger pathway15,16, was transfected into the CD45-negative cell. Although stimulation of the TCR failed to generate Ptdlns-derived second messengers, there was normal activity of the PtdIns pathway when human muscarinic receptor type 1 was stimulated, despite the absence of CD45. These data indicate that CD45 influences a cellular component that is essential for effective coupling of the TCR to the PtdIns second messenger pathway.
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References
Patel, M. D., Samelson, L. E. & Klausner, R. D. J. biol. Chem. 262, 5831–5838 (1987).
Samelson, L. E. & Patel, M. D. Cell 46, 1083–1090 (1986).
Weiss, A. & imboden, J. B. Adv. Immun. 41, 1–38 (1987).
Imboden, J. B., Weiss, A. & Stobo, J. D. J. Immun. 134, 663–665 (1985).
Imboden, J. B. & Stobo, J. D. J. exp. Med. 161, 446–456 (1985).
Thomas, M. L. A. Rev. Immun. 7, 339–369 (1989).
Tonks, N. K., Charbonneau, H., Diltz, C. D., Fischer, E. H. & Walsh, K. A. Biochemistry 27, 8695–8701 (1988).
Kiener, P. A. & Mittler, R. S. J. Immun. 143, 22–28 (1989).
Mustelin, T., Coggeshall, K. M. & Altman, A. Proc. natn. Acad. Sci. U.S.A. 86, 6302–6306 (1989).
Ostergaard, H. L. et al. Proc. natn. Acad. Sci. U.S.A. 86, 8959–8963 (1989).
Pingel, J. T. & Thomas, M. L. Cell 58, 1055–1065 (1989).
Martorell, J., Vilella, R., Borche, L., Rojo, I. & Vives, J. Eur. J. Immun. 17, 1447–1451 (1987).
Mittler, R. S., Greenfield, R. S., Schacter, B. Z., Richard, N. F. & Hoffmann, M. K. J. Immun. 138, 3159–3166 (1987).
Ledbetter, J. A., Tonks, N. K., Fischer, E. H. & Clark, E. A. Proc. natn. Acad. Sci. U.S.A. 85, 8628–8632 (1988).
Peralta, E. G., Ashkenazi, A., Winslow, J. W., Ramachandran, J. & Capon, D. J. Nature 334, 434–437 (1988).
Goldsmith, M. G., Desai, D. M., Shultz, T. & Weiss, A. J. biol. Chem. 264, 17190–17197 (1989).
Lanier, L. L., Ruitenberg, J. J., Allison, J. P. & Weiss, A. J. Immun. 137, 2286–2292 (1986).
Oettgen, H. C., Terhorst, C., Canthley, L. C. & Rosoff, P. M. Cell 40, 583–590 (1985).
Berridge, M. J. & Irvine, R. F. Nature 312, 315–321 (1984).
Akbar, A. N., Terry, L., Timms, A., Beverley, P. C. L. & Janossy, G. J. Immun 140, 2171–2178 (1988).
Thomas, M. L., Reynolds, P. J., Chain, A., Ben-Neriah, Y. & Trowbridge, I. S. Proc. natn. Acad. Sci. U.S.A. 84, 5360–5363 (1987).
Johnson, N. A., Meyer, C. M., Pingel, J. T. & Thomas, M. L. J. biol. Chem. 264, 6220–6229 (1989).
Nathanson, N. M. A. Rev. Neurosci. 10: 195–236 (1987).
Baniyash, M., Gardia-Morales, P., Bonifacino, J. S., Samelson, L. E. & Klausner, R. D. J. biol. Chem. 263, 9874–9878 (1988).
Samelson, L. E., Davidson, W. F., Morse, H. C. & Klausner, R. D. Nature 324, 674–676 (1986).
Weiss, A. & Stobo, J. D. J. exp. Med. 160, 1284–1299 (1984).
Goldsmith, M. G. & Weiss, A. Proc. natn. Acad. Sci. U.S.A. 84, 6879–6883 (1987).
Tsien, R. Y., Pozzan, T. & Rink, T. J. J. Cell Biol. 94, 925–934 (1982).
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Koretzky, G., Picus, J., Thomas, M. et al. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway. Nature 346, 66–68 (1990). https://doi.org/10.1038/346066a0
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DOI: https://doi.org/10.1038/346066a0
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