Home LiteratureArticle Details
PMID: 8459204 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain.

The Journal of experimental medicine ·Vol. 177 ·No. 4 ·1993-04-01 ·Pages 1093-103

Irving BA, Chan AC, Weiss A

Abstract

A conserved sequence motif has been identified in a number of signaling subunits associated with hematopoietic cell antigen receptors. Here, we characterize signaling by a 17 amino acid motif that is triplicated in the T cell antigen receptor zeta chain. Analysis of zeta truncations and constructs containing the isolated motif demonstrates that this motif is sufficient for the induction of both proximal and distal events associated with T cell activation. Stimulation of truncations that contain either one, two, or three copies of the motif results in induction of an identical pattern of tyrosine phosphoproteins. Moreover, triplication of the NH2-terminal zeta motif results in enhanced signaling, suggesting a redundant role in signal amplification for the three motifs in zeta. Finally, we demonstrate the association of a recently identified protein tyrosine kinase ZAP-70 with this motif, and provide evidence for its involvement in zeta function.

MeSH Terms
Amino Acid Sequence CD8 Antigens/genetics,metabolism Cell Line Conserved Sequence Flow Cytometry Humans Membrane Proteins/chemistry,genetics,metabolism Molecular Sequence Data Peptide Fragments/metabolism Precipitin Tests Protein-Tyrosine Kinases/metabolism Receptors, Antigen, T-Cell/chemistry,genetics,metabolism Signal Transduction T-Lymphocytes/metabolism Transfection ZAP-70 Protein-Tyrosine Kinase
Chemicals
CD8 Antigens Membrane Proteins Peptide Fragments Receptors, Antigen, T-Cell antigen T cell receptor, zeta chain Protein-Tyrosine Kinases ZAP-70 Protein-Tyrosine Kinase ZAP70 protein, human
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Irving B A
Department of Physiology, University of California, San Francisco 94143.
Chan A C
Weiss A
References (44)
44 references, click to expand
  1. Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5.
    Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2945-9 PMID: 1372996
  2. 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 PMID: 1705867
  3. Profound block in thymocyte development in mice lacking p56lck.
    Nature. 1992 May 14;357(6374):161-4 PMID: 1579166
  4. Fc epsilon R1-mediated tyrosine phosphorylation of multiple proteins, including phospholipase C gamma 1 and the receptor beta gamma 2 complex, in RBL-2H3 rat basophilic leukemia cells.
    Mol Cell Biol. 1992 Jul;12(7):3176-82 PMID: 1535686
  5. 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):585-93 PMID: 1505025
  6. pp59fyn mutant mice display differential signaling in thymocytes and peripheral T cells.
    Cell. 1992 Sep 4;70(5):741-50 PMID: 1387588
  7. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn.
    Cell. 1992 Sep 4;70(5):751-63 PMID: 1516132
  8. 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):9107-11 PMID: 1409610
  9. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain.
    Cell. 1992 Nov 13;71(4):649-62 PMID: 1423621
  10. p59fyn tyrosine kinase associates with multiple T-cell receptor subunits through its unique amino-terminal domain.
    Mol Cell Biol. 1992 Dec;12(12):5438-46 PMID: 1448076
  11. 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):1284-99 PMID: 6208306
  12. Inositol trisphosphate, a novel second messenger in cellular signal transduction.
    Nature. 1984 Nov 22-28;312(5992):315-21 PMID: 6095092
  13. 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):446-56 PMID: 3919143
  14. Identification of the components of the murine T cell antigen receptor complex.
    Cell. 1985 Nov;43(1):223-31 PMID: 3878228
  15. Isolation and characterization of a T-lymphocyte somatic mutant with altered signal transduction by the antigen receptor.
    Proc Natl Acad Sci U S A. 1987 Oct;84(19):6879-83 PMID: 3309950
  16. Characterization of antigen receptor response elements within the interleukin-2 enhancer.
    Mol Cell Biol. 1988 Apr;8(4):1715-24 PMID: 3260003
  17. Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn).
    Cell. 1991 Apr 19;65(2):281-91 PMID: 2015626
  18. CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line.
    Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453-6 PMID: 1828897
  19. T-cell antigen receptor ligation induces tyrosine phosphorylation of phospholipase C-gamma 1.
    J Biol Chem. 1991 Jul 5;266(19):12135-9 PMID: 2061301
  20. Functional activation of the T-cell antigen receptor induces tyrosine phosphorylation of phospholipase C-gamma 1.
    Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5484-8 PMID: 1712101
  21. 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):15790-6 PMID: 1874735
  22. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A.
    Nature. 1991 Aug 29;352(6338):803-7 PMID: 1715516
  23. The structure and signalling functions of the invariant T cell receptor components.
    Semin Immunol. 1990 Mar;2(2):89-97 PMID: 2151801
  24. T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins.
    Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8905-9 PMID: 1833767
  25. 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):9166-70 PMID: 1717999
  26. Signaling requirements for the expression of the transactivating factor NF-AT in human T lymphocytes.
    Eur J Immunol. 1991 Nov;21(11):2811-9 PMID: 1682154
  27. Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zeta chain.
    Cell. 1992 Mar 6;68(5):889-97 PMID: 1547489
  28. The T cell receptor/CD3 complex: a dynamic protein ensemble.
    Annu Rev Immunol. 1988;6:629-62 PMID: 3289580
  29. 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):9874-8 PMID: 3290215
  30. Identification of a putative regulator of early T cell activation genes.
    Science. 1988 Jul 8;241(4862):202-5 PMID: 3260404
  31. The T cell antigen receptor zeta chain is tyrosine phosphorylated upon activation.
    J Biol Chem. 1988 Dec 5;263(34):18225-30 PMID: 3142873
  32. Contingent genetic regulatory events in T lymphocyte activation.
    Science. 1989 Jan 20;243(4889):355-61 PMID: 2783497
  33. Antigen receptor tail clue.
    Nature. 1989 Mar 30;338(6214):383-4 PMID: 2927501
  34. Biochemical characterization of the eta chain of the T-cell receptor. A unique subunit related to zeta.
    J Biol Chem. 1989 Sep 5;264(25):14812-7 PMID: 2768241
  35. Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation.
    Science. 1989 Dec 22;246(4937):1617-20 PMID: 2595372
  36. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation.
    J Immunol. 1990 Mar 1;144(5):1591-9 PMID: 1689750
  37. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor.
    Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358-62 PMID: 2190221
  38. Family of disulphide-linked dimers containing the zeta and eta chains of the T-cell receptor and the gamma chain of Fc receptors.
    Nature. 1990 Sep 13;347(6289):189-91 PMID: 2203969
  39. Inhibition of tyrosine phosphorylation prevents T-cell receptor-mediated signal transduction.
    Proc Natl Acad Sci U S A. 1990 Oct;87(19):7722-6 PMID: 2217205
  40. Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation.
    Science. 1990 Nov 30;250(4985):1253-6 PMID: 1700866
  41. Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28.
    Science. 1991 Jan 18;251(4991):313-6 PMID: 1846244
  42. Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells.
    Cell. 1991 Feb 8;64(3):511-20 PMID: 1671341
  43. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides.
    Cell. 1991 Mar 8;64(5):1037-46 PMID: 1900456
  44. Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor.
    J Biol Chem. 1992 Apr 25;267(12):8613-9 PMID: 1569106
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1993-04-01
Pages
1093-103
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2190991
Subset
IM
Grants
NIAMS NIH HHS · AR-20684 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com