Home LiteratureArticle Details
PMID: 7506531 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Induction of tyrosine phosphorylation and T-cell activation by vanadate peroxide, an inhibitor of protein tyrosine phosphatases.

The Biochemical journal ·Vol. 297 ( Pt 1) ·1994-01-01 ·Pages 163-73

Imbert V, Peyron JF, Farahi Far D, Mari B, Auberger P, Rossi B

Abstract

Rapid tyrosine phosphorylation of key cellular proteins is a crucial event in the transduction of activation signals to T-lymphocytes. The regulatory role of protein tyrosine phosphatases (PTPases) in this process was explored by studying the effects of a powerful PTPase inhibitor, vanadate peroxide (pervanadate), on the activation cascade of Jurkat human leukaemic T-cells. Pervanadate induced activation of the tyrosine kinases lck and fyn (4- and 3-fold respectively) and a dramatic increase in tyrosine phosphorylation of cellular proteins, notably phospholipase C gamma 1. After this event, we observed a rise in intracellular Ca2+ concentration, corresponding to an influx. This effect required surface expression of the CD45 PTPase and was not observed in CD45-deficient variants of Jurkat cells. In the CD45-negative variant, the effect of pervanadate on tyrosine phosphorylation was globally decreased and some phosphorylated substrates were specifically missing. Pervanadate also stimulated transcription of the c-fos gene and accumulation of its mRNA as well as several other hallmarks of T-lymphocyte activation such as surface expression of the CD69 antigen and the interleukin 2 receptor alpha-chain (CD25). Pervanadate synergized with signals delivered by T-cell antigen receptor engagement or by a phorbol ester to induce interleukin 2 production. Pervanadate activated NF-kappa B, as shown by an increase in DNA-binding activity of this transcription factor. We thus conclude that PTPases play a crucial role in the negative regulation of signal transduction culminating in T-lymphocyte activation. Moreover, induction of tyrosine phosphorylation appears sufficient per se to initiate a complete activation programme.

Related Genes
c-fos
MeSH Terms
Base Sequence Calcium/metabolism Genes, fos Humans Interleukin-2/biosynthesis Kinetics Leukemia Leukocyte Common Antigens/analysis Lymphocyte Activation/drug effects Molecular Sequence Data NF-kappa B/metabolism Phosphorylation Phosphotyrosine Protein Tyrosine Phosphatases/antagonists & inhibitors Protein-Tyrosine Kinases/metabolism RNA, Messenger/biosynthesis Receptors, Interleukin-2/metabolism T-Lymphocytes/immunology,physiology Transcription, Genetic/drug effects Tumor Cells, Cultured Type C Phospholipases/metabolism Tyrosine/analogs & derivatives,metabolism Vanadates/pharmacology
Chemicals
Interleukin-2 NF-kappa B RNA, Messenger Receptors, Interleukin-2 peroxovanadate Phosphotyrosine Vanadates Tyrosine Protein-Tyrosine Kinases Leukocyte Common Antigens Protein Tyrosine Phosphatases Type C Phospholipases Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Imbert V
INSERM U364, Faculté de Médecine, Nice, France.
Peyron J F
Farahi Far D
Mari B
Auberger P
Rossi B
References (60)
60 references, click to expand
  1. Interleukin 2 receptor gene expression in normal human T lymphocytes.
    Proc Natl Acad Sci U S A. 1985 Sep;82(18):6281-5 PMID: 3929255
  2. Genomic sequencing.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 PMID: 6326095
  3. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  4. Peroxide(s) of vanadium: a novel and potent insulin-mimetic agent which activates the insulin receptor kinase.
    Biochem Biophys Res Commun. 1987 Aug 31;147(1):259-66 PMID: 3632668
  5. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.
    Cell. 1988 Apr 22;53(2):211-7 PMID: 3129195
  6. The T cell receptor/CD3 complex: a dynamic protein ensemble.
    Annu Rev Immunol. 1988;6:629-62 PMID: 3289580
  7. Identification and purification of a human immunoglobulin-enhancer-binding protein (NF-kappa B) that activates transcription from a human immunodeficiency virus type 1 promoter in vitro.
    Proc Natl Acad Sci U S A. 1988 Jul;85(13):4700-4 PMID: 3133660
  8. 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):5190-4 PMID: 2455897
  9. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck.
    Cell. 1988 Oct 21;55(2):301-8 PMID: 3262426
  10. I kappa B: a specific inhibitor of the NF-kappa B transcription factor.
    Science. 1988 Oct 28;242(4878):540-6 PMID: 3140380
  11. CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8628-32 PMID: 2973067
  12. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level.
    J Immunol. 1984 Jul;133(1):123-8 PMID: 6327821
  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. Transformation of cells by an inhibitor of phosphatases acting on phosphotyrosine in proteins.
    Cell. 1985 Jul;41(3):707-17 PMID: 2408760
  15. Contingent genetic regulatory events in T lymphocyte activation.
    Science. 1989 Jan 20;243(4889):355-61 PMID: 2783497
  16. Leu 23 induction as an early marker of functional CD3/T cell antigen receptor triggering. Requirement for receptor cross-linking, prolonged elevation of intracellular [Ca++] and stimulation of protein kinase C.
    J Immunol. 1989 Mar 15;142(6):1854-60 PMID: 2466079
  17. T cell activation induces rapid tyrosine phosphorylation of a limited number of cellular substrates.
    J Biol Chem. 1989 Jun 25;264(18):10836-42 PMID: 2786526
  18. CD45-protein tyrosine phosphatase cross-linking inhibits T cell receptor CD3-mediated activation in human T cells.
    J Immunol. 1989 Jul 1;143(1):23-8 PMID: 2525147
  19. cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5257-61 PMID: 2546150
  20. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control.
    Cell. 1989 Jul 28;58(2):227-9 PMID: 2665943
  21. Rapid activation of the T-cell tyrosine protein kinase pp56lck by the CD45 phosphotyrosine phosphatase.
    Proc Natl Acad Sci U S A. 1989 Aug;86(16):6302-6 PMID: 2548204
  22. Pervanadate [peroxide(s) of vanadate] mimics insulin action in rat adipocytes via activation of the insulin receptor tyrosine kinase.
    Biochemistry. 1989 Oct 31;28(22):8864-71 PMID: 2690951
  23. 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
  24. T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation.
    Science. 1990 Mar 30;247(4950):1584-7 PMID: 2138816
  25. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B.
    Nature. 1990 Apr 12;344(6267):678-82 PMID: 2157987
  26. 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
  27. Dephosphorylation and activation of the T cell tyrosine kinase pp56lck by the leukocyte common antigen (CD45).
    Oncogene. 1990 Jun;5(6):809-13 PMID: 2141684
  28. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway.
    Nature. 1990 Jul 5;346(6279):66-8 PMID: 2164155
  29. 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
  30. Tyrosine phosphorylation in T cells is regulated by phosphatase activity: studies with phenylarsine oxide.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9255-9 PMID: 1701256
  31. 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
  32. Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha.
    Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):966-70 PMID: 1992489
  33. Kappa B binding proteins are constitutively expressed in an IL-2 autocrine human T cell line.
    J Immunol. 1991 Apr 1;146(7):2409-16 PMID: 2005404
  34. 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):2037-41 PMID: 1672451
  35. Expression of a novel form of the fyn proto-oncogene in hematopoietic cells.
    New Biol. 1989 Oct;1(1):66-74 PMID: 2488273
  36. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1.
    EMBO J. 1991 Aug;10(8):2247-58 PMID: 2065663
  37. Protein tyrosine phosphatases: a diverse family of intracellular and transmembrane enzymes.
    Science. 1991 Jul 26;253(5018):401-6 PMID: 1650499
  38. Peroxovanadates have full insulin-like effects on glycogen synthesis in normal and insulin-resistant skeletal muscle.
    Biochem J. 1991 Jun 1;276 ( Pt 2):289-92 PMID: 2049062
  39. Receptor protein-tyrosine phosphatase gamma is a candidate tumor suppressor gene at human chromosome region 3p21.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5036-40 PMID: 1711217
  40. T-cell development and transmembrane signaling: changing biological responses through an unchanging receptor.
    Immunol Today. 1991 Feb;12(2):79-85 PMID: 1829360
  41. 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
  42. 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
  43. Nuclear transcription factors that bind to elements of the IL-2 promoter. Induction requirements in primary human T cells.
    J Immunol. 1991 Oct 15;147(8):2734-9 PMID: 1655897
  44. The lymphocyte-specific tyrosine protein kinase p56lck.
    Semin Immunol. 1991 May;3(3):143-52 PMID: 1909593
  45. Mechanism of vanadate-induced activation of tyrosine phosphorylation and of the respiratory burst in HL60 cells. Role of reduced oxygen metabolites.
    Biochem J. 1991 Jun 15;276 ( Pt 3):611-9 PMID: 1712198
  46. 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
  47. CD45. A prototype for transmembrane protein tyrosine phosphatases.
    J Biol Chem. 1991 Dec 15;266(35):23517-20 PMID: 1836211
  48. The CD45 protein tyrosine phosphatase is required for the completion of the activation program leading to lymphokine production in the Jurkat human T cell line.
    Int Immunol. 1991 Dec;3(12):1357-66 PMID: 1838006
  49. 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):661-8 PMID: 1532148
  50. Tyrosine kinase-regulated and inositol phosphate-independent Ca2+ elevation and mobilization in T cells.
    J Biol Chem. 1992 Apr 5;267(10):7154-9 PMID: 1551921
  51. Regulation of the p59fyn protein tyrosine kinase by the CD45 phosphotyrosine phosphatase.
    Eur J Immunol. 1992 May;22(5):1173-8 PMID: 1533589
  52. Peroxides of vanadate induce activation of phospholipase D in HL-60 cells. Role of tyrosine phosphorylation.
    J Biol Chem. 1992 Jun 15;267(17):11908-16 PMID: 1601860
  53. Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes.
    J Biol Chem. 1992 Aug 5;267(22):15836-41 PMID: 1386364
  54. 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
  55. Activation of tyrosine kinase p60fyn following T cell antigen receptor cross-linking.
    J Biol Chem. 1992 Sep 15;267(26):18259-62 PMID: 1526965
  56. Activation of signal transduction in platelets by the tyrosine phosphatase inhibitor pervanadate (vanadyl hydroperoxide).
    Biochem J. 1992 Sep 1;286 ( Pt 2):441-9 PMID: 1530576
  57. Both T cell receptor (TcR)-CD3 complex and CD2 increase the tyrosine kinase activity of p56lck. CD2 can mediate TcR-CD3-independent and CD45-dependent activation of p56lck.
    Eur J Immunol. 1992 Nov;22(11):2915-21 PMID: 1358625
  58. Activation of human peripheral blood T lymphocytes by pharmacological induction of protein-tyrosine phosphorylation.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10306-10 PMID: 1279675
  59. The insulinomimetic agents H2O2 and vanadate stimulate tyrosine phosphorylation of potential target proteins for the insulin receptor kinase in intact cells.
    Biochem J. 1992 Dec 1;288 ( Pt 2):631-5 PMID: 1281409
  60. Human interleukin 2. Detection at the picomolar level by sandwich enzyme immunoassay.
    J Immunol Methods. 1987 Mar 12;97(2):215-20 PMID: 3493295
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2970163
Published
1994-01-01
Pages
163-73
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1137806
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2970163 PMC Full Text View journal details
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: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2