Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1995 Jun 1;14(11):2499–2508. doi: 10.1002/j.1460-2075.1995.tb07247.x

Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.

A C Chan 1, M Dalton 1, R Johnson 1, G H Kong 1, T Wang 1, R Thoma 1, T Kurosaki 1
PMCID: PMC398363  PMID: 7781602

Abstract

ZAP-70 is a protein tyrosine kinase (PTK) required for T-cell development and T-cell antigen receptor (TCR) function. ZAP-70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP-70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP-70 was up-regulated 10-fold when ZAP-70 was co-infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP-70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP-70 is required for antigen receptor-mediated induction of interleukin-2 (IL-2) secretion in lymphocytes.

Full text

PDF
2499

Images in this article

Selected References

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

  1. Agarwal A., Salem P., Robbins K. C. Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling. J Biol Chem. 1993 Jul 25;268(21):15900–15905. [PubMed] [Google Scholar]
  2. Arpaia E., Shahar M., Dadi H., Cohen A., Roifman C. M. Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase. Cell. 1994 Mar 11;76(5):947–958. doi: 10.1016/0092-8674(94)90368-9. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Burkhardt A. L., Stealey B., Rowley R. B., Mahajan S., Prendergast M., Fargnoli J., Bolen J. B. Temporal regulation of non-transmembrane protein tyrosine kinase enzyme activity following T cell antigen receptor engagement. J Biol Chem. 1994 Sep 23;269(38):23642–23647. [PubMed] [Google Scholar]
  5. 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]
  6. Chan A. C., Desai D. M., Weiss A. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annu Rev Immunol. 1994;12:555–592. doi: 10.1146/annurev.iy.12.040194.003011. [DOI] [PubMed] [Google Scholar]
  7. Chan A. C., Iwashima M., Turck C. W., Weiss A. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992 Nov 13;71(4):649–662. doi: 10.1016/0092-8674(92)90598-7. [DOI] [PubMed] [Google Scholar]
  8. Chan A. C., Kadlecek T. A., Elder M. E., Filipovich A. H., Kuo W. L., Iwashima M., Parslow T. G., Weiss A. ZAP-70 deficiency in an autosomal recessive form of severe combined immunodeficiency. Science. 1994 Jun 10;264(5165):1599–1601. doi: 10.1126/science.8202713. [DOI] [PubMed] [Google Scholar]
  9. Chan A. C., van Oers N. S., Tran A., Turka L., Law C. L., Ryan J. C., Clark E. A., Weiss A. Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol. 1994 May 15;152(10):4758–4766. [PubMed] [Google Scholar]
  10. Couture C., Baier G., Altman A., Mustelin T. p56lck-independent activation and tyrosine phosphorylation of p72syk by T-cell antigen receptor/CD3 stimulation. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5301–5305. doi: 10.1073/pnas.91.12.5301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cross F. R., Hanafusa H. Local mutagenesis of Rous sarcoma virus: the major sites of tyrosine and serine phosphorylation of pp60src are dispensable for transformation. Cell. 1983 Sep;34(2):597–607. doi: 10.1016/0092-8674(83)90392-6. [DOI] [PubMed] [Google Scholar]
  12. Davies A. H. Current methods for manipulating baculoviruses. Biotechnology (N Y) 1994 Jan;12(1):47–50. doi: 10.1038/nbt0194-47. [DOI] [PubMed] [Google Scholar]
  13. Duplay P., Thome M., Hervé F., Acuto O. p56lck interacts via its src homology 2 domain with the ZAP-70 kinase. J Exp Med. 1994 Apr 1;179(4):1163–1172. doi: 10.1084/jem.179.4.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ebina Y., Ellis L., Jarnagin K., Edery M., Graf L., Clauser E., Ou J. H., Masiarz F., Kan Y. W., Goldfine I. D. The human insulin receptor cDNA: the structural basis for hormone-activated transmembrane signalling. Cell. 1985 Apr;40(4):747–758. doi: 10.1016/0092-8674(85)90334-4. [DOI] [PubMed] [Google Scholar]
  15. Elder M. E., Lin D., Clever J., Chan A. C., Hope T. J., Weiss A., Parslow T. G. Human severe combined immunodeficiency due to a defect in ZAP-70, a T cell tyrosine kinase. Science. 1994 Jun 10;264(5165):1596–1599. doi: 10.1126/science.8202712. [DOI] [PubMed] [Google Scholar]
  16. Gauen L. K., Zhu Y., Letourneur F., Hu Q., Bolen J. B., Matis L. A., Klausner R. D., Shaw A. S. Interactions of p59fyn and ZAP-70 with T-cell receptor activation motifs: defining the nature of a signalling motif. Mol Cell Biol. 1994 Jun;14(6):3729–3741. doi: 10.1128/mcb.14.6.3729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hubbard S. R., Wei L., Ellis L., Hendrickson W. A. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature. 1994 Dec 22;372(6508):746–754. doi: 10.1038/372746a0. [DOI] [PubMed] [Google Scholar]
  18. Hutchcroft J. E., Geahlen R. L., Deanin G. G., Oliver J. M. Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9107–9111. doi: 10.1073/pnas.89.19.9107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iwashima M., Irving B. A., van Oers N. S., Chan A. C., Weiss A. Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases. Science. 1994 Feb 25;263(5150):1136–1139. doi: 10.1126/science.7509083. [DOI] [PubMed] [Google Scholar]
  20. Kanner S. B., Aruffo A., Chan P. Y. Lymphocyte antigen receptor activation of a focal adhesion kinase-related tyrosine kinase substrate. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10484–10487. doi: 10.1073/pnas.91.22.10484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Katzav S., Sutherland M., Packham G., Yi T., Weiss A. The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav. J Biol Chem. 1994 Dec 23;269(51):32579–32585. [PubMed] [Google Scholar]
  22. Kmiecik T. E., Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell. 1987 Apr 10;49(1):65–73. doi: 10.1016/0092-8674(87)90756-2. [DOI] [PubMed] [Google Scholar]
  23. Koga Y., Caccia N., Toyonaga B., Spolski R., Yanagi Y., Yoshikai Y., Mak T. W. A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases. Eur J Immunol. 1986 Dec;16(12):1643–1646. doi: 10.1002/eji.1830161229. [DOI] [PubMed] [Google Scholar]
  24. Kolanus W., Romeo C., Seed B. T cell activation by clustered tyrosine kinases. Cell. 1993 Jul 16;74(1):171–183. doi: 10.1016/0092-8674(93)90304-9. [DOI] [PubMed] [Google Scholar]
  25. Koyasu S., Tse A. G., Moingeon P., Hussey R. E., Mildonian A., Hannisian J., Clayton L. K., Reinherz E. L. Delineation of a T-cell activation motif required for binding of protein tyrosine kinases containing tandem SH2 domains. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6693–6697. doi: 10.1073/pnas.91.14.6693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kurosaki T., Takata M., Yamanashi Y., Inazu T., Taniguchi T., Yamamoto T., Yamamura H. Syk activation by the Src-family tyrosine kinase in the B cell receptor signaling. J Exp Med. 1994 May 1;179(5):1725–1729. doi: 10.1084/jem.179.5.1725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Law C. L., Sidorenko S. P., Chandran K. A., Draves K. E., Chan A. C., Weiss A., Edelhoff S., Disteche C. M., Clark E. A. Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex. J Biol Chem. 1994 Apr 22;269(16):12310–12319. [PubMed] [Google Scholar]
  28. Luo K. X., Hurley T. R., Sefton B. M. Cyanogen bromide cleavage and proteolytic peptide mapping of proteins immobilized to membranes. Methods Enzymol. 1991;201:149–152. doi: 10.1016/0076-6879(91)01014-s. [DOI] [PubMed] [Google Scholar]
  29. Minoguchi K., Benhamou M., Swaim W. D., Kawakami Y., Kawakami T., Siraganian R. P. Activation of protein tyrosine kinase p72syk by Fc epsilon RI aggregation in rat basophilic leukemia cells. p72syk is a minor component but the major protein tyrosine kinase of pp72. J Biol Chem. 1994 Jun 17;269(24):16902–16908. [PubMed] [Google Scholar]
  30. Perlmutter R. M., Levin S. D., Appleby M. W., Anderson S. J., Alberola-Ila J. Regulation of lymphocyte function by protein phosphorylation. Annu Rev Immunol. 1993;11:451–499. doi: 10.1146/annurev.iy.11.040193.002315. [DOI] [PubMed] [Google Scholar]
  31. Perlmutter R. M., Marth J. D., Lewis D. B., Peet R., Ziegler S. F., Wilson C. B. Structure and expression of lck transcripts in human lymphoid cells. J Cell Biochem. 1988 Oct;38(2):117–126. doi: 10.1002/jcb.240380206. [DOI] [PubMed] [Google Scholar]
  32. Piwnica-Worms H., Saunders K. B., Roberts T. M., Smith A. E., Cheng S. H. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. doi: 10.1016/0092-8674(87)90757-4. [DOI] [PubMed] [Google Scholar]
  33. Samelson L. E., Klausner R. D. Tyrosine kinases and tyrosine-based activation motifs. Current research on activation via the T cell antigen receptor. J Biol Chem. 1992 Dec 15;267(35):24913–24916. [PubMed] [Google Scholar]
  34. Snyder M. A., Bishop J. M., Colby W. W., Levinson A. D. Phosphorylation of tyrosine-416 is not required for the transforming properties and kinase activity of pp60v-src. Cell. 1983 Mar;32(3):891–901. doi: 10.1016/0092-8674(83)90074-0. [DOI] [PubMed] [Google Scholar]
  35. Sullivan S., Wong T. W. A manual sequencing method for identification of phosphorylated amino acids in phosphopeptides. Anal Biochem. 1991 Aug 15;197(1):65–68. doi: 10.1016/0003-2697(91)90356-x. [DOI] [PubMed] [Google Scholar]
  36. Szabo S. J., Gold J. S., Murphy T. L., Murphy K. M. Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: roles for NF-Y and NF-ATc. Mol Cell Biol. 1993 Aug;13(8):4793–4805. doi: 10.1128/mcb.13.8.4793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Takata M., Sabe H., Hata A., Inazu T., Homma Y., Nukada T., Yamamura H., Kurosaki T. Tyrosine kinases Lyn and Syk regulate B cell receptor-coupled Ca2+ mobilization through distinct pathways. EMBO J. 1994 Mar 15;13(6):1341–1349. doi: 10.1002/j.1460-2075.1994.tb06387.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Taniguchi T., Kitagawa H., Yasue S., Yanagi S., Sakai K., Asahi M., Ohta S., Takeuchi F., Nakamura S., Yamamura H. Protein-tyrosine kinase p72syk is activated by thrombin and is negatively regulated through Ca2+ mobilization in platelets. J Biol Chem. 1993 Feb 5;268(4):2277–2279. [PubMed] [Google Scholar]
  39. Taniguchi T., Kobayashi T., Kondo J., Takahashi K., Nakamura H., Suzuki J., Nagai K., Yamada T., Nakamura S., Yamamura H. Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis. J Biol Chem. 1991 Aug 25;266(24):15790–15796. [PubMed] [Google Scholar]
  40. Wange R. L., Isakov N., Burke T. R., Jr, Otaka A., Roller P. P., Watts J. D., Aebersold R., Samelson L. E. F2(Pmp)2-TAM zeta 3, a novel competitive inhibitor of the binding of ZAP-70 to the T cell antigen receptor, blocks early T cell signaling. J Biol Chem. 1995 Jan 13;270(2):944–948. doi: 10.1074/jbc.270.2.944. [DOI] [PubMed] [Google Scholar]
  41. Wange R. L., Malek S. N., Desiderio S., Samelson L. E. Tandem SH2 domains of ZAP-70 bind to T cell antigen receptor zeta and CD3 epsilon from activated Jurkat T cells. J Biol Chem. 1993 Sep 15;268(26):19797–19801. [PubMed] [Google Scholar]
  42. Watts J. D., Affolter M., Krebs D. L., Wange R. L., Samelson L. E., Aebersold R. Identification by electrospray ionization mass spectrometry of the sites of tyrosine phosphorylation induced in activated Jurkat T cells on the protein tyrosine kinase ZAP-70. J Biol Chem. 1994 Nov 25;269(47):29520–29529. [PubMed] [Google Scholar]
  43. Weiss A., Littman D. R. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. doi: 10.1016/0092-8674(94)90334-4. [DOI] [PubMed] [Google Scholar]

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

RESOURCES