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. 1996 Feb 1;183(2):611–620. doi: 10.1084/jem.183.2.611

Dominant-negative zeta-associated protein 70 inhibits T cell antigen receptor signaling

PMCID: PMC2192449  PMID: 8627172

Abstract

Zeta-associated protein (ZAP)-70 is a cytoplasmic protein tyrosine required for T cell antigen receptor (TCR) signaling and development. Mutations in ZAP-70 result in severe combined immunodeficiency in humans. ZAP-70 interacts with the TCR by binding to tyrosine- phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) present in the invariant subunits of the TCR complex. Here we report that two ZAP-70 mutants devoid of kinase activity, generated either by a point mutation in the kinase domain to create an inactive kinase, or by truncation of the entire kinase domain (SH2[N+C]), functioned as dominant-negative mutants to specifically suppress TCR-mediated activation of NFAT, a nuclear factor essential for inducible interleukin 2 gene expression. Biochemical studies with the SH2(N+C) mutant showed that it also blocked early TCR signaling events, such as p95vav tyrosine phosphorylation, extracellular signal-regulated kinase 2 activation, and the association of a number of tyrosine- phosphorylated proteins with growth factor receptor-binding protein 2 (GRB2). The inhibitory effects of the SH2(N+C) mutant revealed that it requires an intact phosphotyrosine-binding site in its COOH-terminal SH2 domain. Using a CD8-zeta chimeric receptor to analyze the interaction of the SH2(N+C) mutant with ITAMs of TCR-zeta, we found that this mutant was constitutively bound to the hyperphosphorylated CD8-zeta chimera. These results indicate that tyrosine-phosphorylated ITAM is the target for the action of this dominant-negative mutant, suggesting that the assembly of a functional receptor signaling complex on ITAMs is a critical proximal TCR signaling event leading to downstream activation.

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Selected References

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  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. Alberola-Ila J., Forbush K. A., Seger R., Krebs E. G., Perlmutter R. M. Selective requirement for MAP kinase activation in thymocyte differentiation. Nature. 1995 Feb 16;373(6515):620–623. doi: 10.1038/373620a0. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bram R. J., Crabtree G. R. Calcium signalling in T cells stimulated by a cyclophilin B-binding protein. Nature. 1994 Sep 22;371(6495):355–358. doi: 10.1038/371355a0. [DOI] [PubMed] [Google Scholar]
  5. Bustelo X. R., Ledbetter J. A., Barbacid M. Product of vav proto-oncogene defines a new class of tyrosine protein kinase substrates. Nature. 1992 Mar 5;356(6364):68–71. doi: 10.1038/356068a0. [DOI] [PubMed] [Google Scholar]
  6. Chan A. C., Dalton M., Johnson R., Kong G. H., Wang T., Thoma R., Kurosaki T. Activation of ZAP-70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function. EMBO J. 1995 Jun 1;14(11):2499–2508. doi: 10.1002/j.1460-2075.1995.tb07247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. Clipstone N. A., Crabtree G. R. Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation. Nature. 1992 Jun 25;357(6380):695–697. doi: 10.1038/357695a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Corey S. J., Burkhardt A. L., Bolen J. B., Geahlen R. L., Tkatch L. S., Tweardy D. J. Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4683–4687. doi: 10.1073/pnas.91.11.4683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Desai D. M., Newton M. E., Kadlecek T., Weiss A. Stimulation of the phosphatidylinositol pathway can induce T-cell activation. Nature. 1990 Nov 1;348(6296):66–69. doi: 10.1038/348066a0. [DOI] [PubMed] [Google Scholar]
  15. Donovan J. A., Wange R. L., Langdon W. Y., Samelson L. E. The protein product of the c-cbl protooncogene is the 120-kDa tyrosine-phosphorylated protein in Jurkat cells activated via the T cell antigen receptor. J Biol Chem. 1994 Sep 16;269(37):22921–22924. [PubMed] [Google Scholar]
  16. Durand D. B., Shaw J. P., Bush M. R., Replogle R. E., Belagaje R., Crabtree G. R. Characterization of antigen receptor response elements within the interleukin-2 enhancer. Mol Cell Biol. 1988 Apr;8(4):1715–1724. doi: 10.1128/mcb.8.4.1715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Emmel E. A., Verweij C. L., Durand D. B., Higgins K. M., Lacy E., Crabtree G. R. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science. 1989 Dec 22;246(4937):1617–1620. doi: 10.1126/science.2595372. [DOI] [PubMed] [Google Scholar]
  19. Evan G. I., Lewis G. K., Ramsay G., Bishop J. M. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. doi: 10.1128/mcb.5.12.3610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fischer K. D., Zmuldzinas A., Gardner S., Barbacid M., Bernstein A., Guidos C. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes. Nature. 1995 Mar 30;374(6521):474–477. doi: 10.1038/374474a0. [DOI] [PubMed] [Google Scholar]
  21. Gelfand E. W., Weinberg K., Mazer B. D., Kadlecek T. A., Weiss A. Absence of ZAP-70 prevents signaling through the antigen receptor on peripheral blood T cells but not on thymocytes. J Exp Med. 1995 Oct 1;182(4):1057–1065. doi: 10.1084/jem.182.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Goldsmith M. A., Desai D. M., Schultz T., Weiss A. Function of a heterologous muscarinic receptor in T cell antigen receptor signal transduction mutants. J Biol Chem. 1989 Oct 15;264(29):17190–17197. [PubMed] [Google Scholar]
  23. Hirasawa N., Scharenberg A., Yamamura H., Beaven M. A., Kinet J. P. A requirement for Syk in the activation of the microtubule-associated protein kinase/phospholipase A2 pathway by Fc epsilon R1 is not shared by a G protein-coupled receptor. J Biol Chem. 1995 May 5;270(18):10960–10967. doi: 10.1074/jbc.270.18.10960. [DOI] [PubMed] [Google Scholar]
  24. Howe L. R., Leevers S. J., Gómez N., Nakielny S., Cohen P., Marshall C. J. Activation of the MAP kinase pathway by the protein kinase raf. Cell. 1992 Oct 16;71(2):335–342. doi: 10.1016/0092-8674(92)90361-f. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Hutchcroft J. E., Harrison M. L., Geahlen R. L. Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor. J Biol Chem. 1992 Apr 25;267(12):8613–8619. [PubMed] [Google Scholar]
  27. 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]
  28. 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]
  29. Izquierdo M., Leevers S. J., Marshall C. J., Cantrell D. p21ras couples the T cell antigen receptor to extracellular signal-regulated kinase 2 in T lymphocytes. J Exp Med. 1993 Oct 1;178(4):1199–1208. doi: 10.1084/jem.178.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jackman J. K., Motto D. G., Sun Q., Tanemoto M., Turck C. W., Peltz G. A., Koretzky G. A., Findell P. R. Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. J Biol Chem. 1995 Mar 31;270(13):7029–7032. doi: 10.1074/jbc.270.13.7029. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Kong G. H., Bu J. Y., Kurosaki T., Shaw A. S., Chan A. C. Reconstitution of Syk function by the ZAP-70 protein tyrosine kinase. Immunity. 1995 May;2(5):485–492. doi: 10.1016/1074-7613(95)90029-2. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Leevers S. J., Marshall C. J. Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein. EMBO J. 1992 Feb;11(2):569–574. doi: 10.1002/j.1460-2075.1992.tb05088.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Levin S. D., Anderson S. J., Forbush K. A., Perlmutter R. M. A dominant-negative transgene defines a role for p56lck in thymopoiesis. EMBO J. 1993 Apr;12(4):1671–1680. doi: 10.1002/j.1460-2075.1993.tb05812.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Madrenas J., Wange R. L., Wang J. L., Isakov N., Samelson L. E., Germain R. N. Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science. 1995 Jan 27;267(5197):515–518. doi: 10.1126/science.7824949. [DOI] [PubMed] [Google Scholar]
  37. Margolis B., Hu P., Katzav S., Li W., Oliver J. M., Ullrich A., Weiss A., Schlessinger J. Tyrosine phosphorylation of vav proto-oncogene product containing SH2 domain and transcription factor motifs. Nature. 1992 Mar 5;356(6364):71–74. doi: 10.1038/356071a0. [DOI] [PubMed] [Google Scholar]
  38. Meisner H., Conway B. R., Hartley D., Czech M. P. Interactions of Cbl with Grb2 and phosphatidylinositol 3'-kinase in activated Jurkat cells. Mol Cell Biol. 1995 Jul;15(7):3571–3578. doi: 10.1128/mcb.15.7.3571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Minami Y., Nakagawa Y., Kawahara A., Miyazaki T., Sada K., Yamamura H., Taniguchi T. Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway. Immunity. 1995 Jan;2(1):89–100. doi: 10.1016/1074-7613(95)90081-0. [DOI] [PubMed] [Google Scholar]
  40. Mizushima S., Nagata S. pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res. 1990 Sep 11;18(17):5322–5322. doi: 10.1093/nar/18.17.5322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Motto D. G., Ross S. E., Jackman J. K., Sun Q., Olson A. L., Findell P. R., Koretzky G. A. In vivo association of Grb2 with pp116, a substrate of the T cell antigen receptor-activated protein tyrosine kinase. J Biol Chem. 1994 Aug 26;269(34):21608–21613. [PubMed] [Google Scholar]
  42. Nel A. E., Hanekom C., Rheeder A., Williams K., Pollack S., Katz R., Landreth G. E. Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C. J Immunol. 1990 Apr 1;144(7):2683–2689. [PubMed] [Google Scholar]
  43. Neumeister E. N., Zhu Y., Richard S., Terhorst C., Chan A. C., Shaw A. S. Binding of ZAP-70 to phosphorylated T-cell receptor zeta and eta enhances its autophosphorylation and generates specific binding sites for SH2 domain-containing proteins. Mol Cell Biol. 1995 Jun;15(6):3171–3178. doi: 10.1128/mcb.15.6.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Owaki H., Varma R., Gillis B., Bruder J. T., Rapp U. R., Davis L. S., Geppert T. D. Raf-1 is required for T cell IL2 production. EMBO J. 1993 Nov;12(11):4367–4373. doi: 10.1002/j.1460-2075.1993.tb06121.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Qian D., Griswold-Prenner I., Rosner M. R., Fitch F. W. Multiple components of the T cell antigen receptor complex become tyrosine-phosphorylated upon activation. J Biol Chem. 1993 Feb 25;268(6):4488–4493. [PubMed] [Google Scholar]
  47. Ravichandran K. S., Lee K. K., Songyang Z., Cantley L. C., Burn P., Burakoff S. J. Interaction of Shc with the zeta chain of the T cell receptor upon T cell activation. Science. 1993 Nov 5;262(5135):902–905. doi: 10.1126/science.8235613. [DOI] [PubMed] [Google Scholar]
  48. Rayter S. I., Woodrow M., Lucas S. C., Cantrell D. A., Downward J. p21ras mediates control of IL-2 gene promoter function in T cell activation. EMBO J. 1992 Dec;11(12):4549–4556. doi: 10.1002/j.1460-2075.1992.tb05556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. Shiue L., Zoller M. J., Brugge J. S. Syk is activated by phosphotyrosine-containing peptides representing the tyrosine-based activation motifs of the high affinity receptor for IgE. J Biol Chem. 1995 May 5;270(18):10498–10502. doi: 10.1074/jbc.270.18.10498. [DOI] [PubMed] [Google Scholar]
  51. Sieh M., Batzer A., Schlessinger J., Weiss A. GRB2 and phospholipase C-gamma 1 associate with a 36- to 38-kilodalton phosphotyrosine protein after T-cell receptor stimulation. Mol Cell Biol. 1994 Jul;14(7):4435–4442. doi: 10.1128/mcb.14.7.4435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Straus D. B., Weiss A. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Cell. 1992 Aug 21;70(4):585–593. doi: 10.1016/0092-8674(92)90428-f. [DOI] [PubMed] [Google Scholar]
  53. Straus D. B., Weiss A. The CD3 chains of the T cell antigen receptor associate with the ZAP-70 tyrosine kinase and are tyrosine phosphorylated after receptor stimulation. J Exp Med. 1993 Nov 1;178(5):1523–1530. doi: 10.1084/jem.178.5.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Takebe Y., Seiki M., Fujisawa J., Hoy P., Yokota K., Arai K., Yoshida M., Arai N. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1988 Jan;8(1):466–472. doi: 10.1128/mcb.8.1.466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. 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]
  56. Tarakhovsky A., Turner M., Schaal S., Mee P. J., Duddy L. P., Rajewsky K., Tybulewicz V. L. Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature. 1995 Mar 30;374(6521):467–470. doi: 10.1038/374467a0. [DOI] [PubMed] [Google Scholar]
  57. 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]
  58. 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]
  59. 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]
  60. 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]
  61. Weiss A., Stobo J. D. Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line. J Exp Med. 1984 Nov 1;160(5):1284–1299. doi: 10.1084/jem.160.5.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Weiss A. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases. Cell. 1993 Apr 23;73(2):209–212. doi: 10.1016/0092-8674(93)90221-b. [DOI] [PubMed] [Google Scholar]
  63. Woodrow M. A., Rayter S., Downward J., Cantrell D. A. p21ras function is important for T cell antigen receptor and protein kinase C regulation of nuclear factor of activated T cells. J Immunol. 1993 May 1;150(9):3853–3861. [PubMed] [Google Scholar]
  64. Woodrow M., Clipstone N. A., Cantrell D. p21ras and calcineurin synergize to regulate the nuclear factor of activated T cells. J Exp Med. 1993 Nov 1;178(5):1517–1522. doi: 10.1084/jem.178.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wu J., Katzav S., Weiss A. A functional T-cell receptor signaling pathway is required for p95vav activity. Mol Cell Biol. 1995 Aug;15(8):4337–4346. doi: 10.1128/mcb.15.8.4337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Zhang R., Alt F. W., Davidson L., Orkin S. H., Swat W. Defective signalling through the T- and B-cell antigen receptors in lymphoid cells lacking the vav proto-oncogene. Nature. 1995 Mar 30;374(6521):470–473. doi: 10.1038/374470a0. [DOI] [PubMed] [Google Scholar]
  67. van Oers N. S., Killeen N., Weiss A. ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells. Immunity. 1994 Nov;1(8):675–685. doi: 10.1016/1074-7613(94)90038-8. [DOI] [PubMed] [Google Scholar]
  68. van Oers N. S., von Boehmer H., Weiss A. The pre-T cell receptor (TCR) complex is functionally coupled to the TCR-zeta subunit. J Exp Med. 1995 Nov 1;182(5):1585–1590. doi: 10.1084/jem.182.5.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]

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