Abstract
The cell surface molecule CD2 has a signaling role in the activation of T lymphocytes and natural killer cells. Because perturbation of CD2 leads to the appearance of tyrosine-phosphorylated proteins, we investigated the possibility that CD2 associates with cytoplasmic protein tyrosine kinases. As determined by in vitro kinase assays and phosphoamino acid analysis, protein tyrosine kinase activity coprecipitated with CD2 from rat T lymphocytes, T lymphoblasts, thymocytes, interleukin-2-activated natural killer cells, and RNK-16 cells (a rat natural killer cell line). In each case, both p56lck and p59fyn were identified in the CD2 immunoprecipitate. In the thymus, the association between CD2 and these kinases occurred predominately in a small subset of thymocytes that had the cell surface phenotype of mature T cells, indicating that the association is a regulated event and occurs late in T-cell ontogeny. The finding that CD2 is associated with p56lck and p59fyn in detergent lysates suggests that interactions with these Src-like protein kinases play a critical role in CD2-mediated signal transduction.
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- Alcover A., Alberini C., Acuto O., Clayton L. K., Transy C., Spagnoli G. C., Moingeon P., Lopez P., Reinherz E. L. Interdependence of CD3-Ti and CD2 activation pathways in human T lymphocytes. EMBO J. 1988 Jul;7(7):1973–1977. doi: 10.1002/j.1460-2075.1988.tb03035.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alcover A., Chang H. C., Sayre P. H., Hussey R. E., Reinherz E. L. The T 11 (CD 2) cDNA encodes a transmembrane protein which expresses T 11(1), T 11(2) and T 11(3) epitopes but which does not independently mediate calcium influx: analysis by gene transfer in a baculovirus system. Eur J Immunol. 1988 Mar;18(3):363–367. doi: 10.1002/eji.1830180307. [DOI] [PubMed] [Google Scholar]
- Alcover A., Weiss M. J., Daley J. F., Reinherz E. L. The T11 glycoprotein is functionally linked to a calcium channel in precursor and mature T-lineage cells. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2614–2618. doi: 10.1073/pnas.83.8.2614. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arulanandam A. R., Koyasu S., Reinherz E. L. T cell receptor-independent CD2 signal transduction in FcR+ cells. J Exp Med. 1991 Apr 1;173(4):859–868. doi: 10.1084/jem.173.4.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bell G. M., Seaman W. E., Niemi E. C., Imboden J. B. The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line. J Exp Med. 1992 Feb 1;175(2):527–536. doi: 10.1084/jem.175.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bockenstedt L. K., Goldsmith M. A., Dustin M., Olive D., Springer T. A., Weiss A. The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor. J Immunol. 1988 Sep 15;141(6):1904–1911. [PubMed] [Google Scholar]
- Boyle W. J., van der Geer P., Hunter T. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 1991;201:110–149. doi: 10.1016/0076-6879(91)01013-r. [DOI] [PubMed] [Google Scholar]
- Brown M. H., Cantrell D. A., Brattsand G., Crumpton M. J., Gullberg M. The CD2 antigen associates with the T-cell antigen receptor CD3 antigen complex on the surface of human T lymphocytes. Nature. 1989 Jun 15;339(6225):551–553. doi: 10.1038/339551a0. [DOI] [PubMed] [Google Scholar]
- Burkhardt A. L., Brunswick M., Bolen J. B., Mond J. J. Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7410–7414. doi: 10.1073/pnas.88.16.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang H. C., Moingeon P., Lopez P., Krasnow H., Stebbins C., Reinherz E. L. Dissection of the human CD2 intracellular domain. Identification of a segment required for signal transduction and interleukin 2 production. J Exp Med. 1989 Jun 1;169(6):2073–2083. doi: 10.1084/jem.169.6.2073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark S. J., Law D. A., Paterson D. J., Puklavec M., Williams A. F. Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies. J Exp Med. 1988 Jun 1;167(6):1861–1872. doi: 10.1084/jem.167.6.1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleveland D. W. Peptide mapping in one dimension by limited proteolysis of sodium dodecyl sulfate-solubilized proteins. Methods Enzymol. 1983;96:222–229. doi: 10.1016/s0076-6879(83)96020-2. [DOI] [PubMed] [Google Scholar]
- Clipstone N. A., Crumpton M. J. Stable expression of the cDNA encoding the human T lymphocyte-specific CD2 antigen in murine L cells. Eur J Immunol. 1988 Oct;18(10):1541–1545. doi: 10.1002/eji.1830181011. [DOI] [PubMed] [Google Scholar]
- Cooke M. P., Abraham K. M., Forbush K. A., Perlmutter R. M. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell. 1991 Apr 19;65(2):281–291. doi: 10.1016/0092-8674(91)90162-r. [DOI] [PubMed] [Google Scholar]
- Danielian S., Fagard R., Alcover A., Acuto O., Fischer S. The tyrosine kinase activity of p56lck is increased in human T cells activated via CD2. Eur J Immunol. 1991 Aug;21(8):1967–1970. doi: 10.1002/eji.1830210828. [DOI] [PubMed] [Google Scholar]
- He Q., Beyers A. D., Barclay A. N., Williams A. F. A role in transmembrane signaling for the cytoplasmic domain of the CD2 T lymphocyte surface antigen. Cell. 1988 Sep 23;54(7):979–984. doi: 10.1016/0092-8674(88)90112-2. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
- Moingeon P., Lucich J. L., McConkey D. J., Letourneur F., Malissen B., Kochan J., Chang H. C., Rodewald H. R., Reinherz E. L. CD3 zeta dependence of the CD2 pathway of activation in T lymphocytes and natural killer cells. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1492–1496. doi: 10.1073/pnas.89.4.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Monostori E., Desai D., Brown M. H., Cantrell D. A., Crumpton M. J. Activation of human T lymphocytes via the CD2 antigen results in tyrosine phosphorylation of T cell antigen receptor zeta-chains. J Immunol. 1990 Feb 1;144(3):1010–1014. [PubMed] [Google Scholar]
- Paterson D. J., Green J. R., Jefferies W. A., Puklavec M., Williams A. F. The MRC OX-44 antigen marks a functionally relevant subset among rat thymocytes. J Exp Med. 1987 Jan 1;165(1):1–13. doi: 10.1084/jem.165.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Samelson L. E., Fletcher M. C., Ledbetter J. A., June C. H. Activation of tyrosine phosphorylation in human T cells via the CD2 pathway. Regulation by the CD45 tyrosine phosphatase. J Immunol. 1990 Oct 15;145(8):2448–2454. [PubMed] [Google Scholar]
- Samelson L. E., Phillips A. F., Luong E. T., Klausner R. D. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358–4362. doi: 10.1073/pnas.87.11.4358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schraven B., Samstag Y., Altevogt P., Meuer S. C. Association of CD2 and CD45 on human T lymphocytes. Nature. 1990 May 3;345(6270):71–74. doi: 10.1038/345071a0. [DOI] [PubMed] [Google Scholar]
- Seed B., Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. doi: 10.1073/pnas.84.10.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sewell W. A., Brown M. H., Dunne J., Owen M. J., Crumpton M. J. Molecular cloning of the human T-lymphocyte surface CD2 (T11) antigen. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8718–8722. doi: 10.1073/pnas.83.22.8718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sewell W. A., Brown M. H., Owen M. J., Fink P. J., Kozak C. A., Crumpton M. J. The murine homologue of the T lymphocyte CD2 antigen: molecular cloning, chromosome assignment and cell surface expression. Eur J Immunol. 1987 Jul;17(7):1015–1020. doi: 10.1002/eji.1830170718. [DOI] [PubMed] [Google Scholar]
- Shaw A. S., Chalupny J., Whitney J. A., Hammond C., Amrein K. E., Kavathas P., Sefton B. M., Rose J. K. Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase. Mol Cell Biol. 1990 May;10(5):1853–1862. doi: 10.1128/mcb.10.5.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siliciano R. F., Pratt J. C., Schmidt R. E., Ritz J., Reinherz E. L. Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein. Nature. 1985 Oct 3;317(6036):428–430. doi: 10.1038/317428a0. [DOI] [PubMed] [Google Scholar]
- Tiefenthaler G., Hünig T., Dustin M. L., Springer T. A., Meuer S. C. Purified lymphocyte function-associated antigen-3 and T11 target structure are active in CD2-mediated T cell stimulation. Eur J Immunol. 1987 Dec;17(12):1847–1850. doi: 10.1002/eji.1830171227. [DOI] [PubMed] [Google Scholar]
- Turner J. M., Brodsky M. H., Irving B. A., Levin S. D., Perlmutter R. M., Littman D. R. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs. Cell. 1990 Mar 9;60(5):755–765. doi: 10.1016/0092-8674(90)90090-2. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Vivier E., Morin P. M., O'Brien C., Schlossman S. F., Anderson P. CD2 is functionally linked to the zeta-natural killer receptor complex. Eur J Immunol. 1991 Apr;21(4):1077–1080. doi: 10.1002/eji.1830210434. [DOI] [PubMed] [Google Scholar]
- Vujanovic N. L., Herberman R. B., Maghazachi A. A., Hiserodt J. C. Lymphokine-activated killer cells in rats. III. A simple method for the purification of large granular lymphocytes and their rapid expansion and conversion into lymphokine-activated killer cells. J Exp Med. 1988 Jan 1;167(1):15–29. doi: 10.1084/jem.167.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams A. F., Barclay A. N., Clark S. J., Paterson D. J., Willis A. C. Similarities in sequences and cellular expression between rat CD2 and CD4 antigens. J Exp Med. 1987 Feb 1;165(2):368–380. doi: 10.1084/jem.165.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Boehmer H. The developmental biology of T lymphocytes. Annu Rev Immunol. 1988;6:309–326. doi: 10.1146/annurev.iy.06.040188.001521. [DOI] [PubMed] [Google Scholar]