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PMID: 8440263 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Association of p56lck with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56lck.

The EMBO journal ·Vol. 12 ·No. 2 ·1993-02-00 ·Pages 759-68

Minami Y, Kono T, Yamada K, Kobayashi N, Kawahara A, Perlmutter RM, Taniguchi T

Abstract

Previous studies demonstrate that p56lck, a member of the src-family of protein tyrosine kinases (PTKs), can physically associate with the interleukin-2 (IL-2) receptor beta chain (IL-2R beta) and that IL-2 receptor engagement stimulates p56lck activity. To examine the mechanisms underlying p56lck PTK activation by IL-2, we established a mouse pro-B cell line, BAF-B03, expressing both IL-2R beta (either the wild-type or mutant forms) and mouse p56lck at high levels. BAF-B03 cells expressing a mutant IL-2R beta chain lacking an 'acidic' region of the cytoplasmic domain, previously shown to be essential for association with p56lck, fail to induce p56lck PTK activation upon IL-2 stimulation. This suggests that the association of p56lck with the IL-2R beta chain, despite its low stoichiometry, is required for the activation of cellular p56lck PTK upon IL-2 stimulation. Intriguingly, BAF-B03 cells expressing an IL-2R beta chain which lacks a different cytoplasmic region, the 'serine-rich' region, also fail to activate p56lck in response to IL-2. Hence, physical association of p56lck with the IL-2R beta chain is not by itself sufficient to permit IL-2-mediated regulation of this PTK. Additional experiments suggest that one result of PTK activation is the accumulation of c-fos and c-jun transcripts.

MeSH Terms
Animals B-Lymphocytes/enzymology Cells, Cultured Enzyme Activation Gene Expression Genes, fos Genes, jun Humans Interleukin-2/metabolism Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Mice Mutation Protein-Tyrosine Kinases/metabolism Receptors, Interleukin-2/genetics,metabolism Signal Transduction
Chemicals
Interleukin-2 Receptors, Interleukin-2 Protein-Tyrosine Kinases Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Minami Y
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kono T
Yamada K
Kobayashi N
Kawahara A
Perlmutter R M
Taniguchi T
References (74)
74 references, click to expand
  1. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization.
    Cell. 1989 Dec 1;59(5):837-45 PMID: 2590941
  2. Human interleukin 2 (IL 2) receptor beta chain allows transduction of IL 2-induced proliferation signal(s) in a murine cell line.
    Eur J Immunol. 1989 Dec;19(12):2375-8 PMID: 2606143
  3. Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.
    Science. 1990 Jan 19;247(4940):324-7 PMID: 2404337
  4. Interleukin 2-induced tyrosine phosphorylation. Interleukin 2 receptor beta is tyrosine phosphorylated.
    J Biol Chem. 1990 Feb 25;265(6):3561-7 PMID: 2303462
  5. Interleukin 2 (IL-2)-induced tyrosine phosphorylation of IL-2 receptor p75.
    J Exp Med. 1990 Mar 1;171(3):637-44 PMID: 2106566
  6. Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily.
    J Exp Med. 1990 Mar 1;171(3):861-73 PMID: 2307934
  7. Murine interleukin 2 receptor beta chain: dysregulated gene expression in lymphoma line EL-4 caused by a promoter insertion.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):1806-10 PMID: 2155425
  8. Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs.
    Cell. 1990 Mar 9;60(5):755-65 PMID: 2107025
  9. Protein tyrosine phosphorylation associated with activation of the interleukin 2 receptor.
    J Biol Chem. 1990 Apr 5;265(10):5690-4 PMID: 1690713
  10. Short related sequences in the cytoplasmic domains of CD4 and CD8 mediate binding to the amino-terminal domain of the p56lck tyrosine protein kinase.
    Mol Cell Biol. 1990 May;10(5):1853-62 PMID: 2109184
  11. Signal transduction by receptors with tyrosine kinase activity.
    Cell. 1990 Apr 20;61(2):203-12 PMID: 2158859
  12. 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
  13. Stimulation of the antigen and interleukin-2 receptors on T lymphocytes activates distinct tyrosine protein kinases.
    J Biol Chem. 1990 Jun 15;265(17):10138-42 PMID: 2351654
  14. The human interleukin-2 receptor beta-chain gene: genomic organization, promoter analysis and chromosomal assignment.
    Nucleic Acids Res. 1990 Jul 11;18(13):3697-703 PMID: 1973832
  15. A new cytokine receptor superfamily.
    Trends Biochem Sci. 1990 Jul;15(7):265-70 PMID: 2166365
  16. Interleukin 2 receptor beta chain expressed in an oligodendroglioma line binds interleukin 2 and delivers growth signal.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6584-8 PMID: 2395860
  17. Cross-linking of T-cell surface molecules CD4 and CD8 stimulates phosphorylation of the lck tyrosine protein kinase at the autophosphorylation site.
    Mol Cell Biol. 1990 Oct;10(10):5305-13 PMID: 2118992
  18. Structural design and molecular evolution of a cytokine receptor superfamily.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934-8 PMID: 2169613
  19. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.
    Cell. 1990 Oct 19;63(2):303-12 PMID: 2208287
  20. Cloning of the gamma chain of the human IL-2 receptor.
    Science. 1992 Jul 17;257(5068):379-82 PMID: 1631559
  21. Selective in vitro growth of T lymphocytes from normal human bone marrows.
    Science. 1976 Sep 10;193(4257):1007-8 PMID: 181845
  22. Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens.
    Eur J Immunol. 1978 Aug;8(8):539-51 PMID: 81133
  23. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen.
    J Exp Med. 1984 Oct 1;160(4):1126-46 PMID: 6090574
  24. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo.
    Cell. 1985 Jul;41(3):727-34 PMID: 3924409
  25. Protein-tyrosine kinases.
    Annu Rev Biochem. 1985;54:897-930 PMID: 2992362
  26. Only high-affinity receptors for interleukin 2 mediate internalization of ligand.
    Proc Natl Acad Sci U S A. 1986 Mar;83(5):1463-6 PMID: 3081898
  27. Molecular analysis of the interleukin-2 system.
    Immunol Rev. 1986 Aug;92:121-33 PMID: 3091480
  28. Isolation of antibodies for phosphotyrosine by immunization with a v-abl oncogene-encoded protein.
    Mol Cell Biol. 1985 Dec;5(12):3640-3 PMID: 2427929
  29. The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells.
    Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394-8 PMID: 3110786
  30. The CD4 associated tyrosine protein kinase p56lck is positively regulated through its site of autophosphorylation.
    Oncogene. 1990 Oct;5(10):1455-62 PMID: 2250907
  31. Molecular cloning and expression of an IL-6 signal transducer, gp130.
    Cell. 1990 Dec 21;63(6):1149-57 PMID: 2261637
  32. Association of B cell antigen receptor with protein tyrosine kinase Lyn.
    Science. 1991 Jan 11;251(4990):192-4 PMID: 1702903
  33. Oncogenes and signal transduction.
    Cell. 1991 Jan 25;64(2):281-302 PMID: 1846320
  34. Interleukin-6 signals activating junB and TIS11 gene transcription in a B-cell hybridoma.
    Mol Cell Biol. 1991 Mar;11(3):1409-18 PMID: 1705005
  35. T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck.
    Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1996-2000 PMID: 2000405
  36. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor.
    Immunol Today. 1990 Nov;11(11):400-6 PMID: 1964053
  37. An associated molecule, p64, with high-affinity interleukin 2 receptor.
    Int Immunol. 1990;2(5):477-80 PMID: 2085489
  38. Signal transduction by interleukin 2 receptor beta chain: importance of the structural integrity as revealed by site-directed mutagenesis and generation of chimeric receptors.
    Int Immunol. 1991 Feb;3(2):149-56 PMID: 2025615
  39. Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association.
    Science. 1991 Jun 14;252(5012):1523-8 PMID: 2047859
  40. The lck tyrosine protein kinase.
    Oncogene. 1991 May;6(5):683-6 PMID: 1905004
  41. Interleukin-2 receptor regulates activation of phosphatidylinositol 3-kinase.
    J Biol Chem. 1991 Aug 5;266(22):14167-70 PMID: 1713578
  42. Leukemia inhibitory factor and interleukin-6 trigger the same immediate early response, including tyrosine phosphorylation, upon induction of myeloid leukemia differentiation.
    Mol Cell Biol. 1991 Sep;11(9):4371-9 PMID: 1908551
  43. Interleukin 2- and polyomavirus middle T antigen-induced modification of phosphatidylinositol 3-kinase activity in activated T lymphocytes.
    Mol Cell Biol. 1991 Sep;11(9):4431-40 PMID: 1652056
  44. Functional domains of the granulocyte colony-stimulating factor receptor.
    EMBO J. 1991 Oct;10(10):2855-65 PMID: 1717255
  45. IL-2 binding activates a tyrosine-phosphorylated phosphatidylinositol-3-kinase.
    J Immunol. 1991 Oct 1;147(7):2202-7 PMID: 1655887
  46. GPI-anchored cell-surface molecules complexed to protein tyrosine kinases.
    Science. 1991 Nov 15;254(5034):1016-9 PMID: 1719635
  47. Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11349-53 PMID: 1662392
  48. c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain.
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2022-6 PMID: 1549560
  49. IL-2 and EGF receptors stimulate the hematopoietic cell cycle via different signaling pathways: demonstration of a novel role for c-myc.
    Cell. 1992 Jul 10;70(1):57-67 PMID: 1535827
  50. Coclustering of CD4 (L3T4) molecule with the T-cell receptor is induced by specific direct interaction of helper T cells and antigen-presenting cells.
    Proc Natl Acad Sci U S A. 1987 Aug;84(16):5888-92 PMID: 2956608
  51. The IL-2 receptor beta chain (p70): role in mediating signals for LAK, NK, and proliferative activities.
    Science. 1987 Oct 2;238(4823):75-8 PMID: 3116668
  52. Interleukin 3-specific tyrosine phosphorylation of a membrane glycoprotein of Mr 150,000 in multi-factor-dependent myeloid cell lines.
    EMBO J. 1987 Dec 20;6(13):3979-84 PMID: 3502088
  53. Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck).
    Mol Cell Biol. 1988 Feb;8(2):540-50 PMID: 3352600
  54. Activation of a tyrosine protein kinase is an early event in the stimulation of T lymphocytes by interleukin-2.
    J Biol Chem. 1988 May 25;263(15):6956-9 PMID: 3259228
  55. Acquisition of transforming properties by FYN, a normal SRC-related human gene.
    Proc Natl Acad Sci U S A. 1988 Jun;85(11):3870-4 PMID: 3287380
  56. Interleukin-2: inception, impact, and implications.
    Science. 1988 May 27;240(4856):1169-76 PMID: 3131876
  57. Hematopoietic growth factors activate the tyrosine phosphorylation of distinct sets of proteins in interleukin-3-dependent murine cell lines.
    Mol Cell Biol. 1988 May;8(5):2214-8 PMID: 3260330
  58. 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
  59. 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
  60. p56lck protein-tyrosine kinase is cytoskeletal and does not bind to polyomavirus middle T antigen.
    J Virol. 1988 Dec;62(12):4673-9 PMID: 3184274
  61. Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation.
    Mol Cell Biol. 1988 Oct;8(10):4353-61 PMID: 3141789
  62. Interleukin 3 binds to a 140-kDa phosphotyrosine-containing cell surface protein.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):7982-6 PMID: 2460860
  63. Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha.
    J Biol Chem. 1989 Apr 5;264(10):5791-8 PMID: 2564392
  64. Lymphocyte activation provokes modification of a lymphocyte-specific protein tyrosine kinase (p56lck).
    J Immunol. 1989 Apr 1;142(7):2430-7 PMID: 2784463
  65. Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies.
    Proc Natl Acad Sci U S A. 1989 Mar;86(6):1982-6 PMID: 2467293
  66. Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro.
    Genes Dev. 1988 Dec;2(12B):1687-99 PMID: 2467839
  67. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's.
    Science. 1989 May 5;244(4904):551-6 PMID: 2785715
  68. 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
  69. Two-dimensional analysis of interleukin 2-regulated tyrosine kinase activation mediated by the p70-75 beta subunit of the interleukin 2 receptor.
    J Biol Chem. 1989 Jul 25;264(21):12562-7 PMID: 2787319
  70. IL-2 regulation of tyrosine kinase activity is mediated through the p70-75 beta-subunit of the IL-2 receptor.
    J Immunol. 1989 Aug 1;143(3):870-6 PMID: 2787350
  71. The multi-subunit interleukin-2 receptor.
    Annu Rev Biochem. 1989;58:875-911 PMID: 2673025
  72. Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family.
    Cell. 1989 Sep 22;58(6):1023-4 PMID: 2550142
  73. The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain.
    Cell. 1989 Nov 17;59(4):627-36 PMID: 2582490
  74. Alterations in tyrosine protein phosphorylation induced by antibody-mediated cross-linking of the CD4 receptor of T lymphocytes.
    Mol Cell Biol. 1989 Oct;9(10):4441-6 PMID: 2479826
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-02-00
Pages
759-68
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413263
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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