Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Jul 1;172(1):347–350. doi: 10.1084/jem.172.1.347

Coclustering CD45 with CD4 or CD8 alters the phosphorylation and kinase activity of p56lck

PMCID: PMC2188152  PMID: 2141630

Abstract

Antibody-mediated CD4 crosslinking results in increased tyrosine phosphorylation and tyrosine kinase activity of the associated p56lck. Treatment with anti-CD4 and anti-Ig also induced the phosphorylation of p56lck in a CD45- mutant cell line, indicating that the increase in phosphotyrosine content of p56lck is not the result of being sequestered from CD45 protein tyrosine phosphatase (PTPase). Antibody- mediated coclustering of CD45 with CD4 inhibited the anti-CD4-induced phosphorylation of p56lck on tyrosine and the concomitant increase in in vitro kinase activity. Similar results were obtained when CD45 was coclustered with CD8 on cytotoxic T cell lines. These observations provide strong evidence that p56lck is a substrate for CD45 in vivo and provide an assay to study the regulation and specificity of CD45 PTPase activity.

Full Text

The Full Text of this article is available as a PDF (507.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Charbonneau H., Tonks N. K., Walsh K. A., Fischer E. H. The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7182–7186. doi: 10.1073/pnas.85.19.7182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Glasebrook A. L., Sarmiento M., Loken M. R., Dialynas D. P., Quintans J., Eisenberg L., Lutz C. T., Wilde D., Fitch F. W. Murine T lymphocyte clones with distinct immunological functions. Immunol Rev. 1981;54:225–266. doi: 10.1111/j.1600-065x.1981.tb00439.x. [DOI] [PubMed] [Google Scholar]
  3. Hurley T. R., Sefton B. M. Analysis of the activity and phosphorylation of the lck protein in lymphoid cells. Oncogene. 1989 Mar;4(3):265–272. [PubMed] [Google Scholar]
  4. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Lotem J., Sachs L. Indirect induction of differentiation of normal and leukemic myeloid cells by recombinant interleukin 1. Leuk Res. 1989;13(1):13–21. doi: 10.1016/0145-2126(89)90026-x. [DOI] [PubMed] [Google Scholar]
  6. Ostergaard H. L., Shackelford D. A., Hurley T. R., Johnson P., Hyman R., Sefton B. M., Trowbridge I. S. Expression of CD45 alters phosphorylation of the lck-encoded tyrosine protein kinase in murine lymphoma T-cell lines. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8959–8963. doi: 10.1073/pnas.86.22.8959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Rudd C. E., Anderson P., Morimoto C., Streuli M., Schlossman S. F. Molecular interactions, T-cell subsets and a role of the CD4/CD8:p56lck complex in human T-cell activation. Immunol Rev. 1989 Oct;111:225–266. doi: 10.1111/j.1600-065x.1989.tb00548.x. [DOI] [PubMed] [Google Scholar]
  8. Rudd C. E., Trevillyan J. M., Dasgupta J. D., Wong L. L., Schlossman S. F. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5190–5194. doi: 10.1073/pnas.85.14.5190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Thomas M. L. The leukocyte common antigen family. Annu Rev Immunol. 1989;7:339–369. doi: 10.1146/annurev.iy.07.040189.002011. [DOI] [PubMed] [Google Scholar]
  10. Trowbridge I. S. Interspecies spleen-myeloma hybrid producing monoclonal antibodies against mouse lymphocyte surface glycoprotein, T200. J Exp Med. 1978 Jul 1;148(1):313–323. doi: 10.1084/jem.148.1.313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Veillette A., Bookman M. A., Horak E. M., Bolen J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. doi: 10.1016/0092-8674(88)90053-0. [DOI] [PubMed] [Google Scholar]
  12. Veillette A., Bookman M. A., Horak E. M., Samelson L. E., Bolen J. B. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989 Mar 16;338(6212):257–259. doi: 10.1038/338257a0. [DOI] [PubMed] [Google Scholar]
  13. Veillette A., Zúiga-Pflücker J. C., Bolen J. B., Kruisbeek A. M. Engagement of CD4 and CD8 expressed on immature thymocytes induces activation of intracellular tyrosine phosphorylation pathways. J Exp Med. 1989 Nov 1;170(5):1671–1680. doi: 10.1084/jem.170.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES