Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1992 Dec;11(13):4887–4897. doi: 10.1002/j.1460-2075.1992.tb05595.x

CD45 tyrosine phosphatase-activated p59fyn couples the T cell antigen receptor to pathways of diacylglycerol production, protein kinase C activation and calcium influx.

M Shiroo 1, L Goff 1, M Biffen 1, E Shivnan 1, D Alexander 1
PMCID: PMC556966  PMID: 1464315

Abstract

The role of the CD45 phosphotyrosine phosphatase in coupling the T cell antigen receptor complex (TCR) to intracellular signals was investigated. CD45- HPB-ALL T cells were transfected with cDNA encoding the CD45RA+B+C- isoform. The tyrosine kinase activity of p59fyn was found to be 65% less in CD45- cells than in CD45+ cells, whereas p56lck kinase activity was comparable in both sub-clones. In CD45- cells the TCR was uncoupled from protein tyrosine phosphorylation, phospholipase C gamma 1 regulation, inositol phosphate production, calcium signals, diacylglycerol production and protein kinase C activation. Restoration of TCR coupling to all these pathways correlated with the increased p59fyn activity observed in CD45-transfected cells. Co-aggregation of CD4- or CD8-p56lck kinase with the TCR in CD45- cells restored TCR-induced protein tyrosine phosphorylation, phospholipase C gamma 1 regulation and calcium signals. Receptor-mediated calcium signals were largely due (60-90%) to Ca2+ influx, and only a minor component (10-40%) was caused by Ca2+ release from intracellular stores. Maximal CD3-mediated Ca2+ influx occurred at CD3 mAb concentrations at which inositol phosphate production was non-detectable. These results indicate that CD45-regulated p59fyn plays a critical role in coupling the TCR to specific intracellular signalling pathways and that CD4- or CD8-p56lck can only restore signal transduction coupling in CD45- cells when brought into close association with the TCR.

Full text

PDF
4887

Images in this article

Selected References

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

  1. Abraham N., Miceli M. C., Parnes J. R., Veillette A. Enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine protein kinase p56lck. Nature. 1991 Mar 7;350(6313):62–66. doi: 10.1038/350062a0. [DOI] [PubMed] [Google Scholar]
  2. Alexander D. R., Cantrell D. A. Kinases and phosphatases in T-cell activation. Immunol Today. 1989 Jun;10(6):200–205. doi: 10.1016/0167-5699(89)90325-3. [DOI] [PubMed] [Google Scholar]
  3. Alexander D. R., Graves J. D., Lucas S. C., Cantrell D. A., Crumpton M. J. A method for measuring protein kinase C activity in permeabilized T lymphocytes by using peptide substrates. Evidence for multiple pathways of kinase activation. Biochem J. 1990 Jun 1;268(2):303–308. doi: 10.1042/bj2680303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alexander D. R., Hexham J. M., Lucas S. C., Graves J. D., Cantrell D. A., Crumpton M. J. A protein kinase C pseudosubstrate peptide inhibits phosphorylation of the CD3 antigen in streptolysin-O-permeabilized human T lymphocytes. Biochem J. 1989 Jun 15;260(3):893–901. doi: 10.1042/bj2600893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Alexander D. R. The role of phosphatases in signal transduction. New Biol. 1990 Dec;2(12):1049–1062. [PubMed] [Google Scholar]
  6. Baniyash M., Garcia-Morales P., Bonifacino J. S., Samelson L. E., Klausner R. D. Disulfide linkage of the zeta and eta chains of the T cell receptor. Possible identification of two structural classes of receptors. J Biol Chem. 1988 Jul 15;263(20):9874–9878. [PubMed] [Google Scholar]
  7. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  9. Bird G. S., Rossier M. F., Hughes A. R., Shears S. B., Armstrong D. L., Putney J. W., Jr Activation of Ca2+ entry into acinar cells by a non-phosphorylatable inositol trisphosphate. Nature. 1991 Jul 11;352(6331):162–165. doi: 10.1038/352162a0. [DOI] [PubMed] [Google Scholar]
  10. Brattsand G., Cantrell D. A., Ward S., Ivars F., Gullberg M. Signal transduction through the T cell receptor-CD3 complex. Evidence for heterogeneity in receptor coupling. J Immunol. 1990 May 15;144(10):3651–3658. [PubMed] [Google Scholar]
  11. Caron L., Abraham N., Pawson T., Veillette A. Structural requirements for enhancement of T-cell responsiveness by the lymphocyte-specific tyrosine protein kinase p56lck. Mol Cell Biol. 1992 Jun;12(6):2720–2729. doi: 10.1128/mcb.12.6.2720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chalupny N. J., Ledbetter J. A., Kavathas P. Association of CD8 with p56lck is required for early T cell signalling events. EMBO J. 1991 May;10(5):1201–1207. doi: 10.1002/j.1460-2075.1991.tb08061.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chan A. C., Irving B. A., Fraser J. D., Weiss A. The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9166–9170. doi: 10.1073/pnas.88.20.9166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  15. Cohen J. J., Duke R. C., Fadok V. A., Sellins K. S. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992;10:267–293. doi: 10.1146/annurev.iy.10.040192.001411. [DOI] [PubMed] [Google Scholar]
  16. Collins T. L., Uniyal S., Shin J., Strominger J. L., Mittler R. S., Burakoff S. J. p56lck association with CD4 is required for the interaction between CD4 and the TCR/CD3 complex and for optimal antigen stimulation. J Immunol. 1992 Apr 1;148(7):2159–2162. [PubMed] [Google Scholar]
  17. 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]
  18. Crabtree G. R. Contingent genetic regulatory events in T lymphocyte activation. Science. 1989 Jan 20;243(4889):355–361. doi: 10.1126/science.2783497. [DOI] [PubMed] [Google Scholar]
  19. Dasgupta J. D., Granja C., Druker B., Lin L. L., Yunis E. J., Relias V. Phospholipase C-gamma 1 association with CD3 structure in T cells. J Exp Med. 1992 Jan 1;175(1):285–288. doi: 10.1084/jem.175.1.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Davidson D., Chow L. M., Fournel M., Veillette A. Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn. J Exp Med. 1992 Jun 1;175(6):1483–1492. doi: 10.1084/jem.175.6.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Deans J. P., Kanner S. B., Torres R. M., Ledbetter J. A. Interaction of CD4:lck with the T cell receptor/CD3 complex induces early signaling events in the absence of CD45 tyrosine phosphatase. Eur J Immunol. 1992 Mar;22(3):661–668. doi: 10.1002/eji.1830220308. [DOI] [PubMed] [Google Scholar]
  22. Dianzani U., Shaw A., al-Ramadi B. K., Kubo R. T., Janeway C. A., Jr Physical association of CD4 with the T cell receptor. J Immunol. 1992 Feb 1;148(3):678–688. [PubMed] [Google Scholar]
  23. Finkel T. H., Cambier J. C., Kubo R. T., Born W. K., Marrack P., Kappler J. W. The thymus has two functionally distinct populations of immature alpha beta + T cells: one population is deleted by ligation of alpha beta TCR. Cell. 1989 Sep 22;58(6):1047–1054. doi: 10.1016/0092-8674(89)90503-5. [DOI] [PubMed] [Google Scholar]
  24. Finkel T. H., Kubo R. T., Cambier J. C. T-cell development and transmembrane signaling: changing biological responses through an unchanging receptor. Immunol Today. 1991 Feb;12(2):79–85. doi: 10.1016/0167-5699(91)90162-M. [DOI] [PubMed] [Google Scholar]
  25. Gardner P., Alcover A., Kuno M., Moingeon P., Weyand C. M., Goronzy J., Reinherz E. L. Triggering of T-lymphocytes via either T3-Ti or T11 surface structures opens a voltage-insensitive plasma membrane calcium-permeable channel: requirement for interleukin-2 gene function. J Biol Chem. 1989 Jan 15;264(2):1068–1076. [PubMed] [Google Scholar]
  26. Geppert T. D., Davis L. S., Gur H., Wacholtz M. C., Lipsky P. E. Accessory cell signals involved in T-cell activation. Immunol Rev. 1990 Oct;117:5–66. doi: 10.1111/j.1600-065x.1990.tb00566.x. [DOI] [PubMed] [Google Scholar]
  27. Glaichenhaus N., Shastri N., Littman D. R., Turner J. M. Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells. Cell. 1991 Feb 8;64(3):511–520. doi: 10.1016/0092-8674(91)90235-q. [DOI] [PubMed] [Google Scholar]
  28. Gullberg M., Noreus K., Brattsand G., Friedrich B., Shingler V. Purification and characterization of a 19-kilodalton intracellular protein. An activation-regulated putative protein kinase C substrate of T lymphocytes. J Biol Chem. 1990 Oct 15;265(29):17499–17505. [PubMed] [Google Scholar]
  29. Haughn L., Gratton S., Caron L., Sékaly R. P., Veillette A., Julius M. Association of tyrosine kinase p56lck with CD4 inhibits the induction of growth through the alpha beta T-cell receptor. Nature. 1992 Jul 23;358(6384):328–331. doi: 10.1038/358328a0. [DOI] [PubMed] [Google Scholar]
  30. Hoth M., Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature. 1992 Jan 23;355(6358):353–356. doi: 10.1038/355353a0. [DOI] [PubMed] [Google Scholar]
  31. Hurley T. R., Luo K., Sefton B. M. Activators of protein kinase C induce dissociation of CD4, but not CD8, from p56lck. Science. 1989 Jul 28;245(4916):407–409. doi: 10.1126/science.2787934. [DOI] [PubMed] [Google Scholar]
  32. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Imboden J. B., Weiss A. The T-cell antigen receptor regulates sustained increases in cytoplasmic free Ca2+ through extracellular Ca2+ influx and ongoing intracellular Ca2+ mobilization. Biochem J. 1987 Nov 1;247(3):695–700. doi: 10.1042/bj2470695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Irvine R. F. 'Quantal' Ca2+ release and the control of Ca2+ entry by inositol phosphates--a possible mechanism. FEBS Lett. 1990 Apr 9;263(1):5–9. doi: 10.1016/0014-5793(90)80692-c. [DOI] [PubMed] [Google Scholar]
  35. Irving B. A., Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891–901. doi: 10.1016/0092-8674(91)90314-o. [DOI] [PubMed] [Google Scholar]
  36. Janeway C. A., Jr, Carding S., Jones B., Murray J., Portoles P., Rasmussen R., Rojo J., Saizawa K., West J., Bottomly K. CD4+ T cells: specificity and function. Immunol Rev. 1988 Jan;101:39–80. doi: 10.1111/j.1600-065x.1988.tb00732.x. [DOI] [PubMed] [Google Scholar]
  37. Janeway C. A., Jr The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation. Annu Rev Immunol. 1992;10:645–674. doi: 10.1146/annurev.iy.10.040192.003241. [DOI] [PubMed] [Google Scholar]
  38. June C. H., Fletcher M. C., Ledbetter J. A., Samelson L. E. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation. J Immunol. 1990 Mar 1;144(5):1591–1599. [PubMed] [Google Scholar]
  39. Kamps M. P., Sefton B. M. Identification of multiple novel polypeptide substrates of the v-src, v-yes, v-fps, v-ros, and v-erb-B oncogenic tyrosine protein kinases utilizing antisera against phosphotyrosine. Oncogene. 1988 Apr;2(4):305–315. [PubMed] [Google Scholar]
  40. Kisielow P., Leiserson W., Von Boehmer H. Differentiation of thymocytes in fetal organ culture: analysis of phenotypic changes accompanying the appearance of cytolytic and interleukin 2-producing cells. J Immunol. 1984 Sep;133(3):1117–1123. [PubMed] [Google Scholar]
  41. Kizaki H., Tadakuma T., Odaka C., Muramatsu J., Ishimura Y. Activation of a suicide process of thymocytes through DNA fragmentation by calcium ionophores and phorbol esters. J Immunol. 1989 Sep 15;143(6):1790–1794. [PubMed] [Google Scholar]
  42. Klausner R. D., Samelson L. E. T cell antigen receptor activation pathways: the tyrosine kinase connection. Cell. 1991 Mar 8;64(5):875–878. doi: 10.1016/0092-8674(91)90310-u. [DOI] [PubMed] [Google Scholar]
  43. Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
  44. Koretzky G. A., Picus J., Schultz T., Weiss A. Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2037–2041. doi: 10.1073/pnas.88.6.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Koretzky G. A., Picus J., Thomas M. L., Weiss A. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway. Nature. 1990 Jul 5;346(6279):66–68. doi: 10.1038/346066a0. [DOI] [PubMed] [Google Scholar]
  46. Ledbetter J. A., June C. H., Martin P. J., Spooner C. E., Hansen J. A., Meier K. E. Valency of CD3 binding and internalization of the CD3 cell-surface complex control T cell responses to second signals: distinction between effects on protein kinase C, cytoplasmic free calcium, and proliferation. J Immunol. 1986 Jun 1;136(11):3945–3952. [PubMed] [Google Scholar]
  47. Ledbetter J. A., June C. H., Rabinovitch P. S., Grossmann A., Tsu T. T., Imboden J. B. Signal transduction through CD4 receptors: stimulatory vs. inhibitory activity is regulated by CD4 proximity to the CD3/T cell receptor. Eur J Immunol. 1988 Apr;18(4):525–532. doi: 10.1002/eji.1830180406. [DOI] [PubMed] [Google Scholar]
  48. Lehninger A. L., Carafoli E. The interaction of La 3+ with mitochondria in relation to respiration-coupled Ca 2+ transport. Arch Biochem Biophys. 1971 Apr;143(2):506–515. doi: 10.1016/0003-9861(71)90235-9. [DOI] [PubMed] [Google Scholar]
  49. Letourneur F., Klausner R. D. Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3 epsilon. Science. 1992 Jan 3;255(5040):79–82. doi: 10.1126/science.1532456. [DOI] [PubMed] [Google Scholar]
  50. Lucas S., Marais R., Graves J. D., Alexander D., Parker P., Cantrell D. A. Heterogeneity of protein kinase C expression and regulation in T lymphocytes. FEBS Lett. 1990 Jan 15;260(1):53–56. doi: 10.1016/0014-5793(90)80064-p. [DOI] [PubMed] [Google Scholar]
  51. Luo K. X., Sefton B. M. Cross-linking of T-cell surface molecules CD4 and CD8 stimulates phosphorylation of the lck tyrosine protein kinase at the autophosphorylation site. Mol Cell Biol. 1990 Oct;10(10):5305–5313. doi: 10.1128/mcb.10.10.5305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. 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]
  53. Mason M. J., Garcia-Rodriguez C., Grinstein S. Coupling between intracellular Ca2+ stores and the Ca2+ permeability of the plasma membrane. Comparison of the effects of thapsigargin, 2,5-di-(tert-butyl)-1,4-hydroquinone, and cyclopiazonic acid in rat thymic lymphocytes. J Biol Chem. 1991 Nov 5;266(31):20856–20862. [PubMed] [Google Scholar]
  54. McCrady C. W., Ely C. M., Westin E., Carchman R. A. Coordination and reversibility of signals for proliferative activation and interleukin-2 mRNA production in resting human T lymphocytes by phorbol ester and calcium ionophore. J Biol Chem. 1988 Dec 5;263(34):18537–18544. [PubMed] [Google Scholar]
  55. Mela L. Interactions of La3+ and local anesthetic drugs with mitochondrial Ca++ and Mn++ uptake. Arch Biochem Biophys. 1968 Feb;123(2):286–293. doi: 10.1016/0003-9861(68)90136-7. [DOI] [PubMed] [Google Scholar]
  56. Miller J. F., Morahan G. Peripheral T cell tolerance. Annu Rev Immunol. 1992;10:51–69. doi: 10.1146/annurev.iy.10.040192.000411. [DOI] [PubMed] [Google Scholar]
  57. Mittler R. S., Goldman S. J., Spitalny G. L., Burakoff S. J. T-cell receptor-CD4 physical association in a murine T-cell hybridoma: induction by antigen receptor ligation. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8531–8535. doi: 10.1073/pnas.86.21.8531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Molina T. J., Kishihara K., Siderovski D. P., van Ewijk W., Narendran A., Timms E., Wakeham A., Paige C. J., Hartmann K. U., Veillette A. Profound block in thymocyte development in mice lacking p56lck. Nature. 1992 May 14;357(6374):161–164. doi: 10.1038/357161a0. [DOI] [PubMed] [Google Scholar]
  59. Mustelin T., Altman A. Dephosphorylation and activation of the T cell tyrosine kinase pp56lck by the leukocyte common antigen (CD45). Oncogene. 1990 Jun;5(6):809–813. [PubMed] [Google Scholar]
  60. Mustelin T., Coggeshall K. M., Isakov N., Altman A. T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation. Science. 1990 Mar 30;247(4950):1584–1587. doi: 10.1126/science.2138816. [DOI] [PubMed] [Google Scholar]
  61. Mustelin T., Pessa-Morikawa T., Autero M., Gassmann M., Andersson L. C., Gahmberg C. G., Burn P. Regulation of the p59fyn protein tyrosine kinase by the CD45 phosphotyrosine phosphatase. Eur J Immunol. 1992 May;22(5):1173–1178. doi: 10.1002/eji.1830220510. [DOI] [PubMed] [Google Scholar]
  62. Nakayama T., Samelson L. E., Nakayama Y., Munitz T. I., Sheard M., June C. H., Singer A. Ligand-stimulated signaling events in immature CD4+CD8+ thymocytes expressing competent T-cell receptor complexes. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9949–9953. doi: 10.1073/pnas.88.22.9949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Niklinska B. B., Yamada H., O'Shea J. J., June C. H., Ashwell J. D. Tyrosine kinase-regulated and inositol phosphate-independent Ca2+ elevation and mobilization in T cells. J Biol Chem. 1992 Apr 5;267(10):7154–7159. [PubMed] [Google Scholar]
  64. 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]
  65. Oettgen H. C., Terhorst C., Cantley L. C., Rosoff P. M. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985 Mar;40(3):583–590. doi: 10.1016/0092-8674(85)90206-5. [DOI] [PubMed] [Google Scholar]
  66. 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]
  67. Ostergaard H. L., Trowbridge I. S. Coclustering CD45 with CD4 or CD8 alters the phosphorylation and kinase activity of p56lck. J Exp Med. 1990 Jul 1;172(1):347–350. doi: 10.1084/jem.172.1.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Peppelenbosch M. P., Tertoolen L. G., de Laat S. W. Epidermal growth factor-activated calcium and potassium channels. J Biol Chem. 1991 Oct 25;266(30):19938–19944. [PubMed] [Google Scholar]
  69. Pingel J. T., Thomas M. L. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell. 1989 Sep 22;58(6):1055–1065. doi: 10.1016/0092-8674(89)90504-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Premack B. A., Gardner P. Role of ion channels in lymphocytes. J Clin Immunol. 1991 Sep;11(5):225–238. doi: 10.1007/BF00918180. [DOI] [PubMed] [Google Scholar]
  71. Ratcliffe M. J., Coggeshall K. M., Newell M. K., Julius M. H. T cell receptor aggregation, but not dimerization, induces increased cytosolic calcium concentrations and reveals a lack of stable association between CD4 and the T cell receptor. J Immunol. 1992 Mar 15;148(6):1643–1651. [PubMed] [Google Scholar]
  72. Rothenberg E. V. Death and transfiguration of cortical thymocytes: a reconsideration. Immunol Today. 1990 Apr;11(4):116–119. doi: 10.1016/0167-5699(90)90047-d. [DOI] [PubMed] [Google Scholar]
  73. 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]
  74. Salmerón A., Sánchez-Madrid F., Ursa M. A., Fresno M., Alarcón B. A conformational epitope expressed upon association of CD3-epsilon with either CD3-delta or CD3-gamma is the main target for recognition by anti-CD3 monoclonal antibodies. J Immunol. 1991 Nov 1;147(9):3047–3052. [PubMed] [Google Scholar]
  75. Samelson L. E., Harford J. B., Klausner R. D. Identification of the components of the murine T cell antigen receptor complex. Cell. 1985 Nov;43(1):223–231. doi: 10.1016/0092-8674(85)90027-3. [DOI] [PubMed] [Google Scholar]
  76. 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]
  77. Sancho J., Silverman L. B., Castigli E., Ahern D., Laudano A. P., Terhorst C., Geha R. S., Chatila T. A. Developmental regulation of transmembrane signaling via the T cell antigen receptor/CD3 complex in human T lymphocytes. J Immunol. 1992 Mar 1;148(5):1315–1321. [PubMed] [Google Scholar]
  78. Sawamura S., Ase K., Berry N., Kikkawa U., McCaffrey P. G., Minowada J., Nishizuka Y. Expression of protein kinase C subspecies in human leukemia-lymphoma cell lines. FEBS Lett. 1989 Apr 24;247(2):353–357. doi: 10.1016/0014-5793(89)81369-9. [DOI] [PubMed] [Google Scholar]
  79. Secrist J. P., Karnitz L., Abraham R. T. T-cell antigen receptor ligation induces tyrosine phosphorylation of phospholipase C-gamma 1. J Biol Chem. 1991 Jul 5;266(19):12135–12139. [PubMed] [Google Scholar]
  80. Sefton B. M. The lck tyrosine protein kinase. Oncogene. 1991 May;6(5):683–686. [PubMed] [Google Scholar]
  81. Seong R. H., Chamberlain J. W., Parnes J. R. Signal for T-cell differentiation to a CD4 cell lineage is delivered by CD4 transmembrane region and/or cytoplasmic tail. Nature. 1992 Apr 23;356(6371):718–720. doi: 10.1038/356718a0. [DOI] [PubMed] [Google Scholar]
  82. Shivnan E., Biffen M., Shiroo M., Pratt E., Glennie M., Alexander D. Does co-aggregation of the CD45 and CD3 antigens inhibit T cell antigen receptor complex-mediated activation of phospholipase C and protein kinase C? Eur J Immunol. 1992 Apr;22(4):1055–1062. doi: 10.1002/eji.1830220427. [DOI] [PubMed] [Google Scholar]
  83. Streuli M., Morimoto C., Schrieber M., Schlossman S. F., Saito H. Characterization of CD45 and CD45R monoclonal antibodies using transfected mouse cell lines that express individual human leukocyte common antigens. J Immunol. 1988 Dec 1;141(11):3910–3914. [PubMed] [Google Scholar]
  84. 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]
  85. Truneh A., Albert F., Golstein P., Schmitt-Verhulst A. M. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature. 1985 Jan 24;313(6000):318–320. doi: 10.1038/313318a0. [DOI] [PubMed] [Google Scholar]
  86. 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]
  87. 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]
  88. Wange R. L., Kong A. N., Samelson L. E. A tyrosine-phosphorylated 70-kDa protein binds a photoaffinity analogue of ATP and associates with both the zeta chain and CD3 components of the activated T cell antigen receptor. J Biol Chem. 1992 Jun 15;267(17):11685–11688. [PubMed] [Google Scholar]
  89. Weaver C. T., Pingel J. T., Nelson J. O., Thomas M. L. CD8+ T-cell clones deficient in the expression of the CD45 protein tyrosine phosphatase have impaired responses to T-cell receptor stimuli. Mol Cell Biol. 1991 Sep;11(9):4415–4422. doi: 10.1128/mcb.11.9.4415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Wegener A. M., Letourneur F., Hoeveler A., Brocker T., Luton F., Malissen B. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell. 1992 Jan 10;68(1):83–95. doi: 10.1016/0092-8674(92)90208-t. [DOI] [PubMed] [Google Scholar]
  91. Weiss A. Molecular and genetic insights into T cell antigen receptor structure and function. Annu Rev Genet. 1991;25:487–510. doi: 10.1146/annurev.ge.25.120191.002415. [DOI] [PubMed] [Google Scholar]
  92. Yarden Y., Ullrich A. Growth factor receptor tyrosine kinases. Annu Rev Biochem. 1988;57:443–478. doi: 10.1146/annurev.bi.57.070188.002303. [DOI] [PubMed] [Google Scholar]
  93. Zamoyska R., Derham P., Gorman S. D., von Hoegen P., Bolen J. B., Veillette A., Parnes J. R. Inability of CD8 alpha' polypeptides to associate with p56lck correlates with impaired function in vitro and lack of expression in vivo. Nature. 1989 Nov 16;342(6247):278–281. doi: 10.1038/342278a0. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES