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PMID: 7683423 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Reconstitution of functional interleukin 2 receptor complexes on fibroblastoid cells: involvement of the cytoplasmic domain of the gamma chain in two distinct signaling pathways.

Asao H, Takeshita T, Ishii N, Kumaki S, Nakamura M, Sugamura K

Abstract

We have previously shown that the interleukin 2 (IL-2) receptor gamma chain is a member of the cytokine receptor superfamily and is indispensable for the formation of receptor complexes with high and intermediate affinities for IL-2. The present study demonstrates that the alpha beta gamma heterotrimer and beta gamma heterodimer complexes of IL-2 receptor reconstituted on murine fibroblast L929 cells can transduce IL-2-mediated signals for activation of tyrosine kinase and for induction of c-myc, c-fos, and c-jun expression. A mutant of the gamma chain lacking the C-terminal 68 amino acids in its cytoplasmic region showed a loss of such signal-transducing ability when incorporated into the IL-2 receptor complexes but brought no effect on IL-2 binding and IL-2 internalization. Another mutant, with a C-terminal deletion of 30 amino acids, retained the ability to activate a tyrosine kinase and to induce c-myc expression but lost the ability to induce c-fos and c-jun expression. These results suggest that at least two distinct signals, one for c-myc induction, which parallels tyrosine kinase activation, and the other for c-fos and c-jun induction, can be transduced from the IL-2 receptor complexes reconstituted on fibroblastoid cells.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Binding Sites Blotting, Northern Codon Fibroblasts/immunology,metabolism Humans Interleukin-2/metabolism,pharmacology Kinetics L Cells Macromolecular Substances Mice Molecular Sequence Data Oligodeoxyribonucleotides Phosphates/metabolism Phosphoproteins/isolation & purification,metabolism Phosphorylation Phosphotyrosine Plasmids RNA/genetics,isolation & purification RNA, Messenger/isolation & purification,metabolism Receptors, Interleukin-2/genetics,metabolism Recombinant Proteins/metabolism Signal Transduction Terminator Regions, Genetic Transfection Tyrosine/analogs & derivatives,metabolism
Chemicals
Codon Interleukin-2 Macromolecular Substances Oligodeoxyribonucleotides Phosphates Phosphoproteins RNA, Messenger Receptors, Interleukin-2 Recombinant Proteins Phosphotyrosine Tyrosine RNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Asao H
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Takeshita T
Ishii N
Kumaki S
Nakamura M
Sugamura K
References (39)
39 references, click to expand
  1. A new cytokine receptor superfamily.
    Trends Biochem Sci. 1990 Jul;15(7):265-70 PMID: 2166365
  2. Interleukin 2 (IL-2)-induced tyrosine phosphorylation of IL-2 receptor p75.
    J Exp Med. 1990 Mar 1;171(3):637-44 PMID: 2106566
  3. Regulation of interleukin 2-dependent growth responses by glycosylphosphatidylinositol molecules.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9421-5 PMID: 2147515
  4. Glycosylphosphatidylinositol: a candidate system for interleukin-2 signal transduction.
    Science. 1991 Jan 4;251(4989):78-81 PMID: 1824727
  5. Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1227-31 PMID: 1996324
  6. 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
  7. Involvement of ras p21 protein in signal-transduction pathways from interleukin 2, interleukin 3, and granulocyte/macrophage colony-stimulating factor, but not from interleukin 4.
    Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3314-8 PMID: 1826565
  8. The evidence for the IL-2 receptor beta chain processing from p70 to p75.
    Int Immunol. 1990;2(5):469-72 PMID: 2128185
  9. An associated molecule, p64, with high-affinity interleukin 2 receptor.
    Int Immunol. 1990;2(5):477-80 PMID: 2085489
  10. Interleukin-2-triggered Raf-1 expression, phosphorylation, and associated kinase activity increase through G1 and S in CD3-stimulated primary human T cells.
    Mol Cell Biol. 1991 May;11(5):2794-803 PMID: 1708096
  11. IL-2 receptor subunit, p75: direct demonstration of its IL-2 binding ability by using a novel monoclonal antibody.
    Int Immunol. 1989;1(4):373-7 PMID: 2489034
  12. 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
  13. Interleukin-2 receptor regulates activation of phosphatidylinositol 3-kinase.
    J Biol Chem. 1991 Aug 5;266(22):14167-70 PMID: 1713578
  14. 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
  15. IL-2 binding activates a tyrosine-phosphorylated phosphatidylinositol-3-kinase.
    J Immunol. 1991 Oct 1;147(7):2202-7 PMID: 1655887
  16. An associated molecule, p64, with IL-2 receptor beta chain. Its possible involvement in the formation of the functional intermediate-affinity IL-2 receptor complex.
    J Immunol. 1992 Apr 1;148(7):2154-8 PMID: 1545122
  17. Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line.
    Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2674-8 PMID: 1557373
  18. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase.
    Nature. 1992 Jul 2;358(6381):70-3 PMID: 1614535
  19. IL-2-dependent in vivo and in vitro tyrosine phosphorylation of IL-2 receptor gamma chain.
    FEBS Lett. 1992 Jun 15;304(2-3):141-5 PMID: 1618313
  20. 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
  21. Cloning of the gamma chain of the human IL-2 receptor.
    Science. 1992 Jul 17;257(5068):379-82 PMID: 1631559
  22. Cell type-specific tyrosine phosphorylation of IL-2 receptor beta chain in response to IL-2.
    FEBS Lett. 1992 Sep 21;310(1):22-6 PMID: 1526279
  23. Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation.
    EMBO J. 1992 Oct;11(10):3541-9 PMID: 1396555
  24. Interleukin 2-induced activation of Ras requires two domains of interleukin 2 receptor beta subunit, the essential region for growth stimulation and Lck-binding domain.
    J Biol Chem. 1992 Dec 15;267(35):25423-7 PMID: 1460037
  25. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor.
    Nature. 1984 Oct 18-24;311(5987):626-31 PMID: 6090948
  26. Molecular cloning of cDNA encoding human interleukin-2 receptor.
    Nature. 1984 Oct 18-24;311(5987):631-5 PMID: 6090949
  27. Cloning, sequence and expression of human interleukin-2 receptor.
    Nature. 1984 Dec 20-1985 Jan 2;312(5996):768-71 PMID: 6096720
  28. High-affinity receptor-mediated internalization and degradation of interleukin 2 in human T cells.
    J Exp Med. 1986 Mar 1;163(3):550-62 PMID: 3005464
  29. Interleukin 2 (IL-2) rapidly induces phosphorylation of a cellular protein, pp67, in an IL-2 dependent murine cell line.
    Biochem Biophys Res Commun. 1986 Mar 13;135(2):487-94 PMID: 3485973
  30. Interleukin-2 induction of T-cell G1 progression and c-myb expression.
    Science. 1986 Jul 11;233(4760):203-6 PMID: 3523754
  31. Biochemical and molecular events associated with interleukin 2 regulation of lymphocyte proliferation.
    Immunol Rev. 1986 Aug;92:49-65 PMID: 3091482
  32. Recombinant interleukin 2 regulates levels of c-myc mRNA in a cloned murine T lymphocyte.
    Mol Cell Biol. 1985 Dec;5(12):3361-8 PMID: 3879814
  33. Interleukin 2 and diacylglycerol stimulate phosphorylation of 40 S ribosomal S6 protein. Correlation with increased protein synthesis and S6 kinase activation.
    J Biol Chem. 1987 Apr 5;262(10):4624-30 PMID: 3494010
  34. 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
  35. 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
  36. Activation of endogenous c-fos proto-oncogene expression by human T-cell leukemia virus type I-encoded p40tax protein in the human T-cell line, Jurkat.
    J Virol. 1989 Aug;63(8):3220-6 PMID: 2501514
  37. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130.
    Cell. 1989 Aug 11;58(3):573-81 PMID: 2788034
  38. 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
  39. 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
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1993-05-01
Pages
4127-31
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46459
Subset
IM
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