Abstract
LYMPHOCYTE-specific tyrosine protein kinase p56lck is physically associated with CD4 and CDS T-cell surface molecules, suggesting that it may transduce CD4/CD8-triggered tyrosine phosphorylation signals during antigen stimulation1,2. Indeed, antibody-mediated aggregation of CD4 (to mimic interaction with its ligand, major histocompatibility complex (MHC) class II molecules), rapidly elevates the kinase activity of p56lck (refs 3, 4) and is associated with marked changes in tyrosine protein phosphorylation4-6. Genetic analyses suggest that the interaction of CD4/CD8 with p56lck results in a positive signal during antigen-induced T-cell activation7-10. To evaluate directly the role of p56lck in T-cell activation, we introduced a constitutively activated form of Lck protein (tyrosine 505 to phenylalanine 505 mutant; refs 11-13) in a CD4-negative, MHC-class II restricted mouse T-cell hybridoma14. We report here that, as for transfection of CD410,15,16, expression of the Lck mutant enhanced T-lymphocyte responsiveness. This finding provides direct evidence that p56lck can positively regulate T-cell functions and that it mediates at least some of the effects of CD4 and CDS on T-cell activation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Veillette, A., Bookman, M. A., Horak, E. M. & Bolen, J. B. Cell 55, 301–308 (1988).
Rudd, C. E., Trevillyan, J. M., Dasgupta, J. D., Wong, L. L. & Schlossman, S. F. Proc. natn. Acad. Sci. U.S.A. 85, 5190–5194 (1988).
Veillette, A., Bookman, M. A., Horak, E. M. Samelson, L. E. & Bolen, J. B. Nature 338, 257–259 (1989).
Luo, K. & Sefton, B. M. Molec. cell. Biol. 10, 5305–5313 (1990).
Veillette, A., Bolen, J. B. & Bookman, M. A. Molec. cell. Biol. 9, 4441–4446 (1989).
Veillette, A., Zuniga-Pflucker, J. C., Bolen, J. B. & Kruisbeek, A. M. J. exp. Med. 170, 1671–1680 (1989).
Sleckman, B. P. et al. J. Immun. 141, 49–54 (1988).
Zamoyska, R. et al. Nature 342, 278–281 (1989).
Letourneur, F. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2339–2343 (1990).
Miceli, M. C., von Hoegen, P. & Parnes, J. R. Proc. natn. Acad. Sci. U.S.A. 88, 2623–2627 (1991).
Amrein, K. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 85, 4247–4251 (1988).
Marth, J. D. et al. Molec. cell. Biol. 8, 540–550 (1988).
Abraham, N. & Veillette, A. Molec. cell. Biol. 10, 5197–5206 (1990).
Reske-Kunz, A. B. & Rude, E. Eur. J. Immun. 15, 1048–1054 (1085).
Ballhausen, W. G. et al. J. exp. Med. 167, 1493–1498 (1988).
Parnes, J. R., von Hoegen, P., Miceli, M. C. & Zamoyska, R. Cold Spring Harb. Symp. quant. Biol. 54, 649–655 (1989).
Mustelin, T., Coggeshall, K. M., Isakov, N. & Altman, A. Science 247, 1584–1587 (1990).
June, C. H. et al. Proc. natn. Acad. Sci. U.S.A. 87, 7722–7726 (1990).
June, C. H., Fletcher, M. C., Ledbetter, J. A. & Samelson, L. E. J. Immun. 144, 1591–1599 (1990).
Gay, D. et al. Nature 328, 626–629 (1987).
Anderson, P., Blue, M. L. & Schlossman, S. F. J. Immun. 140, 1732–1737 (1988).
Gallagher, P. F., de St. Groth, B. F. & Miller, J. F. A. P. Proc. natn. Acad. Sci. U.S.A. 86, 10044–10048 (1989).
Saizawa, K., Rojo, J. & Janeway, C. A. Nature 328, 260–263 (1987).
Ostergaard, H. L. et al. Proc. natn. Acad. Sci. U.S.A. 86, 8959–8963 (1989).
Reynolds, P. J. et al. Molec. cell. Biol. 10, 4266–4270 (1990).
Einspahr, K. J., Abraham, R. T., Dick, C. J. & Leibson, P. J. J. Immun. 145, 1490–1497 (1990).
Miller, A. D. & Rosman, G. J. BioTechniques 7, 980–990 (1989).
Albritton, L. M., Tseng, L., Scadden, D. & Cunningham, J. M. Cell 57, 659–666 (1989).
Louie, R. R. et al. J. Virol. 62, 4673–4679 (1988).
Mossman, T. R. J. immunol. Meth. 65, 55–63 (1983).
Koch, C. A., Moran, M., Sadowski, I. & Pawson, T. Molec. cell. Biol. 9, 4131–4140 (1989).
Staerz, U. D., Rammensee, H., Benedetto, J. D. & Bevan, M. J. J. Immun. 134, 3994–4000 (1985).
Wilde, D. B., Marrack, P., Kappler, J., Dialynas, D. P. & Fitch, F. W. J. Immun. 131, 2178–2183 (1983).
Leo, O., Foo, M., Sachs, D. H., Samelson, L. E. & Bluestone, J. A. Proc. natn. Acad. Sci. U.S.A. 84, 1374–1378 (1987).
Kubo, R. T., Born, W., Kappler, J. W., Marrack, P. & Pigeon, M. J. Immun. 142, 2736–2742 (1989).
Gunter, K. C., Malek, T. R. & Shevach, E. M. J. exp. Med. 159, 716–730 (1984).
Springer, T., Galfre, G., Secher, D. S. & Milstein, C. Eur. J. Immun. 8, 539–551 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Abraham, N., Miceli, M., Parnes, J. et al. Enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine protein kinase p56lck. Nature 350, 62–66 (1991). https://doi.org/10.1038/350062a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/350062a0
This article is cited by
-
CD47 masks pro-phagocytic ligands in cis on tumor cells to suppress antitumor immunity
Nature Immunology (2023)
-
Lymphocyte-Specific Protein Tyrosine Kinase Contributes to Spontaneous Regression of Liver Fibrosis may by Interacting with Suppressor of Cytokine Signaling 1
Inflammation (2023)
-
SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin
Nature (2017)
-
A DNA-binding mutant of TAL1 cooperates with LMO2 to cause T cell leukemia in mice
Oncogene (2011)
-
Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation
Nature Cell Biology (2003)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
