Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation (original) (raw)

Abstract

The lymphocyte-specific tyrosine protein kinase p56lck is abundantly expressed in L3T4+ (CD4+) and Lyt-2+ (CD8+) T-lymphocytes, where it is predominantly phosphorylated in vivo on the carboxy-terminal tyrosine residue 505 (Y-505). Upon exposure to activating signals (mitogenic lectins, antibodies to the T-cell receptor), the p56lck expressed in normal cloned murine T-cells is modified into a product which migrates at approximately 59 kilodaltons on sodium dodecyl sulfate-polyacrylamide gels and which possesses several amino-terminal serine phosphorylations. The changes in both mobility and amino-terminal phosphorylation can be reproduced by known activators of protein kinase C (4 alpha-phorbol 12 beta-myristate, dioctanoylglycerol), suggesting that this signal transduction pathway (or related pathways) mediates at least part of these events. Interestingly, agents raising intracellular calcium (such as A23187) cause the appearance of several of these amino-terminal phosphorylation changes but do not cause the pronounced shift in electrophoretic mobility. These data suggest that at least two serine kinase systems are implicated in the alterations of p56lck associated with T-cell activation and that the lck gene product plays a critical role in normal T-cell physiology.

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Selected References

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  1. Bolen J. B., Veillette A., Schwartz A. M., Deseau V., Rosen N. Analysis of pp60c-src in human colon carcinoma and normal human colon mucosal cells. Oncogene Res. 1987 Jul;1(2):149–168. [PubMed] [Google Scholar]
  2. Bookman M. A., Swerdlow R., Matis L. A. Adoptive chemoimmunotherapy of murine leukemia with helper T lymphocyte clones. J Immunol. 1987 Nov 1;139(9):3166–3170. [PubMed] [Google Scholar]
  3. Casnellie J. E., Harrison M. L., Hellstrom K. E., Krebs E. G. A lymphoma cell line expressing elevated levels of tyrosine protein kinase activity. J Biol Chem. 1983 Sep 10;258(17):10738–10742. [PubMed] [Google Scholar]
  4. Casnellie J. E., Lamberts R. J. Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes. J Biol Chem. 1986 Apr 15;261(11):4921–4925. [PubMed] [Google Scholar]
  5. Casnellie J. E. Sites of in vivo phosphorylation of the T cell tyrosine protein kinase in LSTRA cells and their alteration by tumor-promoting phorbol esters. J Biol Chem. 1987 Jul 15;262(20):9859–9864. [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Cooper J. A., Gould K. L., Cartwright C. A., Hunter T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986 Mar 21;231(4744):1431–1434. doi: 10.1126/science.2420005. [DOI] [PubMed] [Google Scholar]
  8. Gould K. L., Woodgett J. R., Cooper J. A., Buss J. E., Shalloway D., Hunter T. Protein kinase C phosphorylates pp60src at a novel site. Cell. 1985 Oct;42(3):849–857. doi: 10.1016/0092-8674(85)90281-8. [DOI] [PubMed] [Google Scholar]
  9. Gray P. W., Goeddel D. V. Cloning and expression of murine immune interferon cDNA. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5842–5846. doi: 10.1073/pnas.80.19.5842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heckford S. E., Gelmann E. P., Agnor C. L., Jacobson S., Zinn S., Matis L. A. Distinct signals are required for proliferation and lymphokine gene expression in murine T cell clones. J Immunol. 1986 Dec 1;137(11):3652–3663. [PubMed] [Google Scholar]
  11. Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kawakami T., Kawakami Y., Aaronson S. A., Robbins K. C. Acquisition of transforming properties by FYN, a normal SRC-related human gene. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3870–3874. doi: 10.1073/pnas.85.11.3870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koga Y., Kimura N., Minowada J., Mak T. W. Expression of the human T-cell-specific tyrosine kinase YT16 (lck) message in leukemic T-cell lines. Cancer Res. 1988 Feb 15;48(4):856–859. [PubMed] [Google Scholar]
  14. Ledbetter J. A., Gentry L. E., June C. H., Rabinovitch P. S., Purchio A. F. Stimulation of T cells through the CD3/T-cell receptor complex: role of cytoplasmic calcium, protein kinase C translocation, and phosphorylation of pp60c-src in the activation pathway. Mol Cell Biol. 1987 Feb;7(2):650–656. doi: 10.1128/mcb.7.2.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ledbetter J. A., June C. H., Grosmaire L. S., Rabinovitch P. S. Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1384–1388. doi: 10.1073/pnas.84.5.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leo O., Foo M., Sachs D. H., Samelson L. E., Bluestone J. A. Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374–1378. doi: 10.1073/pnas.84.5.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Manger B., Weiss A., Imboden J., Laing T., Stobo J. D. The role of protein kinase C in transmembrane signaling by the T cell antigen receptor complex. Effects of stimulation with soluble or immobilized CD3 antibodies. J Immunol. 1987 Oct 15;139(8):2755–2760. [PubMed] [Google Scholar]
  18. Marth J. D., Cooper J. A., King C. S., Ziegler S. F., Tinker D. A., Overell R. W., Krebs E. G., Perlmutter R. M. Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck). Mol Cell Biol. 1988 Feb;8(2):540–550. doi: 10.1128/mcb.8.2.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marth J. D., Lewis D. B., Wilson C. B., Gearn M. E., Krebs E. G., Perlmutter R. M. Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases. EMBO J. 1987 Sep;6(9):2727–2734. doi: 10.1002/j.1460-2075.1987.tb02566.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Marth J. D., Overell R. W., Meier K. E., Krebs E. G., Perlmutter R. M. Translational activation of the lck proto-oncogene. Nature. 1988 Mar 10;332(6160):171–173. doi: 10.1038/332171a0. [DOI] [PubMed] [Google Scholar]
  21. Marth J. D., Peet R., Krebs E. G., Perlmutter R. M. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. doi: 10.1016/0092-8674(85)90169-2. [DOI] [PubMed] [Google Scholar]
  22. Meuer S. C., Hodgdon J. C., Hussey R. E., Protentis J. P., Schlossman S. F., Reinherz E. L. Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J Exp Med. 1983 Sep 1;158(3):988–993. doi: 10.1084/jem.158.3.988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  24. Ohno S., Akita Y., Konno Y., Imajoh S., Suzuki K. A novel phorbol ester receptor/protein kinase, nPKC, distantly related to the protein kinase C family. Cell. 1988 Jun 3;53(5):731–741. doi: 10.1016/0092-8674(88)90091-8. [DOI] [PubMed] [Google Scholar]
  25. Ralston R., Bishop J. M. The product of the protooncogene c-src is modified during the cellular response to platelet-derived growth factor. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7845–7849. doi: 10.1073/pnas.82.23.7845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rosoff P. M., Burakoff S. J., Greenstein J. L. The role of the L3T4 molecule in mitogen and antigen-activated signal transduction. Cell. 1987 Jun 19;49(6):845–853. doi: 10.1016/0092-8674(87)90622-2. [DOI] [PubMed] [Google Scholar]
  27. Taylor M. V., Metcalfe J. C., Hesketh T. R., Smith G. A., Moore J. P. Mitogens increase phosphorylation of phosphoinositides in thymocytes. 1984 Nov 29-Dec 5Nature. 312(5993):462–465. doi: 10.1038/312462a0. [DOI] [PubMed] [Google Scholar]
  28. Veillette A., Foss F. M., Sausville E. A., Bolen J. B., Rosen N. Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines. Oncogene Res. 1987 Sep-Oct;1(4):357–374. [PubMed] [Google Scholar]
  29. Veillette A., Horak I. D., Bolen J. B. Post-translational alterations of the tyrosine kinase p56lck in response to activators of protein kinase C. Oncogene Res. 1988 May;2(4):385–401. [PubMed] [Google Scholar]
  30. Voronova A. F., Sefton B. M. Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion. Nature. 1986 Feb 20;319(6055):682–685. doi: 10.1038/319682a0. [DOI] [PubMed] [Google Scholar]
  31. Weiss A., Imboden J., Hardy K., Manger B., Terhorst C., Stobo J. The role of the T3/antigen receptor complex in T-cell activation. Annu Rev Immunol. 1986;4:593–619. doi: 10.1146/annurev.iy.04.040186.003113. [DOI] [PubMed] [Google Scholar]
  32. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  33. de Graaf P. W., Horak E., Bookman M. A. Adoptive immunotherapy of syngeneic murine leukemia is enhanced by the combination of recombinant IFN-gamma and a tumor-specific cytotoxic T cell clone. J Immunol. 1988 Apr 15;140(8):2853–2857. [PubMed] [Google Scholar]