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PMID: 3119327 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases.

The EMBO journal ·Vol. 6 ·No. 9 ·1987-09-00 ·Pages 2727-34

Marth JD, Lewis DB, Wilson CB, Gearn ME, Krebs EG, Perlmutter RM

Abstract

The lymphocyte-specific protein tyrosine kinase pp56lck, encoded by a member of the src gene family, is implicated in the control of T-cell growth and differentiation. Purified resting human T lymphocytes contain appreciable levels of lck mRNA and of pp56lck. Upon activation of these T cells, levels of lck mRNA and of pp56lck promptly decline. These reductions in lck mRNA and protein expression are closely correlated with the induction of lymphokine production. Both require identical stimuli and follow a similar time course of response. Down-regulation of lck expression, however, is not correlated with proliferation. Our results provide an example of regulation of a src-like protein tyrosine kinase in a normal fully differentiated cell population and suggest that modulation of lck RNA and protein expression is an important feature of the lymphocyte activation sequence leading to lymphokine production.

MeSH Terms
Adult Gene Expression Regulation Genes Genes, Regulator Humans Lymphocyte Activation Oncogene Protein pp60(v-src) Protein-Tyrosine Kinases/genetics RNA, Messenger/genetics Retroviridae Proteins/genetics T-Lymphocytes/enzymology,immunology Transcription, Genetic
Chemicals
RNA, Messenger Retroviridae Proteins Protein-Tyrosine Kinases Oncogene Protein pp60(v-src)
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Marth J D
Howard Hughes Medical Institute, Seattle, WA.
Lewis D B
Wilson C B
Gearn M E
Krebs E G
Perlmutter R M
References (65)
65 references, click to expand
  1. Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells.
    Mol Cell Biol. 1987 Jun;7(6):2267-75 PMID: 3496523
  2. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5459-63 PMID: 3526330
  3. The kinetics of neutrophilic leukocytes in health and in disease.
    Semin Hematol. 1967 Oct;4(4):359-86 PMID: 4864987
  4. The early uptake of radioactive calcium by human lymphocytes treated with phytohaemagglutinin.
    Immunology. 1971 Sep;21(3):509-16 PMID: 5568327
  5. Induction of increased calcium uptake in mouse T lymphocytes by concanavalin A and its modulation by cyclic nucleotides.
    Nature. 1975 May 29;255(5507):378-82 PMID: 165431
  6. Temperature-sensitive changes in surface modulating assemblies of fibroblasts transformed by mutants of Rous sarcoma virus.
    Proc Natl Acad Sci U S A. 1976 Jun;73(6):2047-51 PMID: 180536
  7. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  8. Signal requirements for T lymphocyte activation. I. Replacement of macrophage function with phorbol myristic acetate.
    J Immunol. 1979 Oct;123(4):1749-54 PMID: 314470
  9. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  10. Activity of human blood leukocytes against Toxoplasma gondii.
    J Infect Dis. 1979 Dec;140(6):890-5 PMID: 541523
  11. Use of glutaraldehyde as a coupling agent for proteins and peptides.
    Methods Enzymol. 1980;70(A):159-65 PMID: 6252416
  12. A suggested mechanism for T lymphocyte activation: implications on the acquisition of functional reactivities.
    Immunol Rev. 1980;51:61-91 PMID: 6159302
  13. Transformation by Rous sarcoma virus: a cellular substrate for transformation-specific protein phosphorylation contains phosphotyrosine.
    Cell. 1980 Oct;21(3):821-8 PMID: 6159984
  14. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product.
    Cell. 1980 Oct;21(3):829-36 PMID: 6254669
  15. A calcium hypothesis for the control of cell growth.
    Biochem Soc Symp. 1980;45:1-26 PMID: 6783043
  16. Vinculin: a cytoskeletal target of the transforming protein of Rous sarcoma virus.
    Cell. 1981 Apr;24(1):165-74 PMID: 6263485
  17. Mechanism of T cell activation: role and functional relationship of HLA-DR antigens and interleukins.
    Immunol Rev. 1982;63:73-110 PMID: 6804370
  18. Phosphorylation of synthetic peptides by a tyrosine protein kinase from the particulate fraction of a lymphoma cell line.
    Proc Natl Acad Sci U S A. 1982 Jan;79(2):282-6 PMID: 6804939
  19. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
    J Biol Chem. 1982 Jul 10;257(13):7847-51 PMID: 7085651
  20. Synergistic functions of phorbol ester and calcium in serotonin release from human platelets.
    Biochem Biophys Res Commun. 1983 Apr 29;112(2):778-86 PMID: 6405748
  21. Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation.
    J Biol Chem. 1983 Jun 10;258(11):6701-4 PMID: 6406488
  22. Three T cell hybridomas do not contain detectable heavy chain variable gene transcripts.
    J Exp Med. 1983 Jul 1;158(1):210-27 PMID: 6190978
  23. A practical approach for quantitating specific mRNAs by solution hybridization.
    Anal Biochem. 1983 Jun;131(2):385-93 PMID: 6614474
  24. Aldosterone secretion: effect of phorbol ester and A23187.
    Biochem Biophys Res Commun. 1983 Oct 31;116(2):555-62 PMID: 6418161
  25. A possible role of protein kinase C in signal-induced lysosomal enzyme release.
    Biochem Biophys Res Commun. 1983 Oct 31;116(2):743-50 PMID: 6228230
  26. Insulin secretion: combined effects of phorbol ester and A23187.
    Biochem Biophys Res Commun. 1983 Dec 16;117(2):448-55 PMID: 6229253
  27. pp60c-src is developmentally regulated in the neural retina.
    Cell. 1984 Feb;36(2):249-57 PMID: 6198092
  28. Synergistic effect of A23187 and a phorbol ester on amylase secretion from rabbit pancreatic acini.
    FEBS Lett. 1984 May 7;170(1):64-8 PMID: 6202551
  29. The interleukin-2 T-cell system: a new cell growth model.
    Science. 1984 Jun 22;224(4655):1312-6 PMID: 6427923
  30. Synergistic action of protein kinase C and calcium for histamine release from rat peritoneal mast cells.
    Biochem Biophys Res Commun. 1984 Jun 15;121(2):573-8 PMID: 6203533
  31. A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum.
    FEBS Lett. 1984 Sep 17;175(1):165-9 PMID: 6434345
  32. Stimulation of tyrosine phosphorylation in lectin treated human lymphocytes.
    Biochem Biophys Res Commun. 1984 Nov 14;124(3):682-9 PMID: 6508776
  33. Higher tyrosine protein kinase activity in resting lymphocytes than in proliferating normal or leukaemic blood cells.
    Biochem Biophys Res Commun. 1984 Nov 14;124(3):766-73 PMID: 6542362
  34. Autocrine growth induced by src-related oncogenes in transformed chicken myeloid cells.
    Cell. 1984 Dec;39(3 Pt 2):439-45 PMID: 6096003
  35. Covalently bound myristate in a lymphoma tyrosine protein kinase.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7679-82 PMID: 6595656
  36. Activation of a human T cell line: a two-stimulus requirement in the pretranslational events involved in the coordinate expression of interleukin 2 and gamma-interferon genes.
    J Immunol. 1985 Mar;134(3):1599-603 PMID: 3918105
  37. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester.
    Nature. 1985 Jan 24-30;313(6000):318-20 PMID: 3918270
  38. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx.
    Cell. 1985 Mar;40(3):583-90 PMID: 2578888
  39. pp60c-src in the developing cerebellum.
    Mol Cell Biol. 1985 Jan;5(1):27-32 PMID: 3920510
  40. Viral oncogenes.
    Cell. 1985 Aug;42(1):23-38 PMID: 2990725
  41. Protein-tyrosine kinases.
    Annu Rev Biochem. 1985;54:897-930 PMID: 2992362
  42. Antigen-dependent increase in cytosolic free calcium in specific human T-lymphocyte clones.
    Nature. 1985 Aug 8-14;316(6028):545-7 PMID: 3875796
  43. Neurones express high levels of a structurally modified, activated form of pp60c-src.
    Nature. 1985 Aug 8-14;316(6028):554-7 PMID: 2412121
  44. Differentiation of PC12 phaeochromocytoma cells induced by v-src oncogene.
    Nature. 1985 Aug 8-14;316(6028):557-9 PMID: 2993898
  45. The nucleotide sequence and the tissue-specific expression of Drosophila c-src.
    Cell. 1985 Oct;42(3):831-40 PMID: 2996778
  46. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA.
    Cell. 1985 Dec;43(2 Pt 1):393-404 PMID: 2416464
  47. fgr proto-oncogene mRNA induced in B lymphocytes by Epstein-Barr virus infection.
    Nature. 1986 Jan 16-22;319(6050):238-40 PMID: 3003578
  48. p60c-src activity detected in the chromaffin granule membrane.
    Biochem Biophys Res Commun. 1986 Jan 29;134(2):736-42 PMID: 3511908
  49. Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies.
    J Clin Invest. 1986 Mar;77(3):860-7 PMID: 3081575
  50. Reduced interferon-gamma mRNA levels in human neonates. Evidence for an intrinsic T cell deficiency independent of other genes involved in T cell activation.
    J Exp Med. 1986 Apr 1;163(4):1018-23 PMID: 3081678
  51. Lymphokine and nonlymphokine mRNA levels in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A.
    J Exp Med. 1986 Apr 1;163(4):922-37 PMID: 2419474
  52. Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin.
    Mol Cell Biol. 1987 Jun;7(6):2276-85 PMID: 3453117
  53. Lethal effect of the Abelson murine leukemia virus transforming gene product.
    Cell. 1981 Dec;27(3 Pt 2):477-86 PMID: 6101202
  54. Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity.
    Proc Natl Acad Sci U S A. 1986 Feb;83(4):852-6 PMID: 2419901
  55. Tumor promoters cause changes in the state of phosphorylation and apparent molecular weight of a tyrosine protein kinase in T lymphocytes.
    J Biol Chem. 1986 Apr 15;261(11):4921-5 PMID: 2420795
  56. The role of the T3/antigen receptor complex in T-cell activation.
    Annu Rev Immunol. 1986;4:593-619 PMID: 2939858
  57. Sequential expression of protooncogenes during lectin-stimulated mitogenesis of normal human lymphocytes.
    Proc Natl Acad Sci U S A. 1986 Jun;83(11):3982-6 PMID: 3012540
  58. The cDNA sequence for the protein-tyrosine kinase substrate p36 (calpactin I heavy chain) reveals a multidomain protein with internal repeats.
    Cell. 1986 Jul 18;46(2):201-12 PMID: 3013423
  59. The role of the accessory cell in mitogen-stimulated human T cell gene expression.
    J Immunol. 1986 Aug 1;137(3):764-9 PMID: 3088109
  60. Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion.
    Nature. 1986 Feb 20-26;319(6055):682-5 PMID: 3081813
  61. Localization of a lymphocyte-specific protein tyrosine kinase gene (lck) at a site of frequent chromosomal abnormalities in human lymphomas.
    Proc Natl Acad Sci U S A. 1986 Oct;83(19):7400-4 PMID: 3463975
  62. Accumulation of c-src mRNA is developmentally regulated in embryonic neural retina.
    Mol Cell Biol. 1986 Nov;6(11):4109-11 PMID: 2432396
  63. The role of protein kinase C in transmembrane signalling.
    Annu Rev Cell Biol. 1986;2:149-78 PMID: 3548765
  64. T-cell activation.
    Annu Rev Cell Biol. 1986;2:231-53 PMID: 3548767
  65. Phosphorylation of talin at tyrosine in Rous sarcoma virus-transformed cells.
    Mol Cell Biol. 1987 Jan;7(1):371-8 PMID: 3031468
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1987-09-00
Pages
2727-34
Language
English
Region
England
NLM ID
8208664
PMCID
PMC553696
Subset
IM
Grants
NIAID NIH HHS · AI16760 · United States
NICHD NIH HHS · HD06706 · United States
NICHD NIH HHS · HD18184 · United States
External Links
PubMed source PMC Full Text View journal details
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