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PMID: 7681987 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Isolation of interleukin 2-induced immediate-early genes.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 7 ·1993-04-01 ·Pages 2719-23

Beadling C, Johnson KW, Smith KA

Abstract

Clonal expansion of antigen-reactive T lymphocytes is driven by the lymphokine interleukin 2 (IL-2). To further elucidate the mechanisms of IL-2 action, we have utilized a differential hybridization procedure to clone IL-2-induced immediate-early genes from an IL-2-stimulated human T-cell cDNA library. To increase the frequency of IL-2-induced transcripts represented in the library, the protein synthesis inhibitor cycloheximide was included during the 2-hr IL-2 stimulation to superinduce gene expression, and the uridine analogue 4-thiouridine was utilized to enable selective purification of newly synthesized transcripts. From the enriched library, we have isolated eight IL-2-induced genes, six of which represent previously unrecognized human sequences. Northern blot analysis revealed that the induction of seven of the genes is specific to the IL-2-mediated G1 "progression" phase of the cell cycle, in that only one gene is also induced during the T-cell receptor-triggered G0-G1 "competence" phase. These results indicate that the effects of IL-2 are mediated by the specific induction of a number of immediate-early genes and provide a means with which to further delineate the mechanisms whereby IL-2 stimulates T-lymphocyte proliferation and differentiation. The methods described in this report should also be of general utility in the dissection of the signaling pathways activated by diverse cytokine receptors.

MeSH Terms
Base Sequence Blotting, Northern CD3 Complex/physiology Cells, Cultured Cycloheximide/pharmacology DNA/genetics,isolation & purification DNA Replication Gene Expression/drug effects Gene Library Humans Interleukin-2/pharmacology Kinetics RNA/genetics,isolation & purification Receptors, Antigen, T-Cell/physiology Recombinant Proteins/pharmacology T-Lymphocytes/drug effects,physiology
Chemicals
CD3 Complex Interleukin-2 Receptors, Antigen, T-Cell Recombinant Proteins RNA DNA Cycloheximide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Beadling C
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755-3833.
Johnson K W
Smith K A
References (54)
54 references, click to expand
  1. Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors.
    J Exp Med. 1990 May 1;171(5):1509-26 PMID: 1692080
  2. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition.
    Cell. 1992 Aug 21;70(4):631-45 PMID: 1505028
  3. cDNA cloning and characterization of interleukin 2-induced genes in a cloned T helper lymphocyte.
    J Biol Chem. 1990 Jul 25;265(21):12671-8 PMID: 2142689
  4. A new cytokine receptor superfamily.
    Trends Biochem Sci. 1990 Jul;15(7):265-70 PMID: 2166365
  5. Haemopoietic receptors and helical cytokines.
    Immunol Today. 1990 Oct;11(10):350-4 PMID: 2171545
  6. The immediate-early growth response in regenerating liver and insulin-stimulated H-35 cells: comparison with serum-stimulated 3T3 cells and identification of 41 novel immediate-early genes.
    Mol Cell Biol. 1991 Jan;11(1):381-90 PMID: 1986233
  7. Regulation of interleukin-2 gene enhancer activity by the T cell accessory molecule CD28.
    Science. 1991 Jan 18;251(4991):313-6 PMID: 1846244
  8. Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C.
    Mol Cell Biol. 1991 Feb;11(2):1009-16 PMID: 1990262
  9. Sequence and expression of a cDNA encoding MyD118: a novel myeloid differentiation primary response gene induced by multiple cytokines.
    Oncogene. 1991 Jan;6(1):165-7 PMID: 1899477
  10. Molecular cloning of a novel human cdc2/CDC28-like protein kinase.
    J Biol Chem. 1991 Feb 25;266(6):3402-7 PMID: 1704889
  11. 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
  12. 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
  13. T cell antigen receptor activation pathways: the tyrosine kinase connection.
    Cell. 1991 Mar 8;64(5):875-8 PMID: 1848158
  14. The cytoplasmic region of the erythropoietin receptor contains nonoverlapping positive and negative growth-regulatory domains.
    Mol Cell Biol. 1991 Apr;11(4):1980-7 PMID: 1848667
  15. T-cell growth factor-mediated T-cell proliferation.
    Ann N Y Acad Sci. 1979;332:423-32 PMID: 316981
  16. T-cell growth factor.
    Immunol Rev. 1980;51:337-57 PMID: 7000676
  17. Molecular cloning of gene sequences regulated by platelet-derived growth factor.
    Cell. 1983 Jul;33(3):939-47 PMID: 6872001
  18. Transient expression of interleukin 2 receptors. Consequences for T cell growth.
    J Exp Med. 1983 Dec 1;158(6):1895-911 PMID: 6606011
  19. Molecular cloning of hormone-responsive genes from the yeast Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1984 Feb;81(4):1144-8 PMID: 6366798
  20. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway.
    Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509-13 PMID: 6231642
  21. The interleukin-2 T-cell system: a new cell growth model.
    Science. 1984 Jun 22;224(4655):1312-6 PMID: 6427923
  22. Interleukin 2-induced lymphocyte proliferation is independent of increases in cytosolic-free calcium concentrations.
    J Immunol. 1985 Apr;134(4):2431-5 PMID: 3919094
  23. Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.
    J Exp Med. 1986 Feb 1;163(2):270-84 PMID: 2935591
  24. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells.
    EMBO J. 1985 Dec 1;4(12):3145-51 PMID: 3841511
  25. Interleukin 2 does not induce phosphatidylinositol hydrolysis in activated T cells.
    J Immunol. 1986 Apr 15;136(8):3019-24 PMID: 3082978
  26. 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
  27. Interleukin-2 induction of T-cell G1 progression and c-myb expression.
    Science. 1986 Jul 11;233(4760):203-6 PMID: 3523754
  28. The cDNA sequence and gene analysis of the human pim oncogene.
    Gene. 1987;54(1):105-11 PMID: 3475233
  29. Improved tools for biological sequence comparison.
    Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444-8 PMID: 3162770
  30. Interleukin-2: inception, impact, and implications.
    Science. 1988 May 27;240(4856):1169-76 PMID: 3131876
  31. Identification of the human pim-1 gene product as a 33-kilodalton cytoplasmic protein with tyrosine kinase activity.
    Mol Cell Biol. 1988 Apr;8(4):1498-503 PMID: 2837645
  32. Complexity of the early genetic response to growth factors in mouse fibroblasts.
    Mol Cell Biol. 1988 May;8(5):2140-8 PMID: 2898731
  33. Selective isolation of newly synthesized mammalian mRNA after in vivo labeling with 4-thiouridine or 6-thioguanosine.
    Anal Biochem. 1988 May 15;171(1):166-72 PMID: 3407913
  34. Protein kinase C is required for responses to T cell receptor ligands but not to interleukin-2 in T cells.
    Cell. 1988 Oct 7;55(1):101-12 PMID: 3262423
  35. Interleukin-2 induces proliferation of T lymphocyte mutants lacking protein kinase C.
    Cell. 1988 Oct 7;55(1):91-100 PMID: 2844411
  36. Regulation of pim and myb mRNA accumulation by interleukin 2 and interleukin 3 in murine hematopoietic cell lines.
    J Biol Chem. 1988 Nov 25;263(33):17615-20 PMID: 3263373
  37. DNA damage-inducible transcripts in mammalian cells.
    Proc Natl Acad Sci U S A. 1988 Dec;85(23):8800-4 PMID: 3194391
  38. Contingent genetic regulatory events in T lymphocyte activation.
    Science. 1989 Jan 20;243(4889):355-61 PMID: 2783497
  39. Expression cloning of the murine erythropoietin receptor.
    Cell. 1989 Apr 21;57(2):277-85 PMID: 2539263
  40. Complexity of the primary genetic response to mitogenic activation of human T cells.
    Mol Cell Biol. 1989 Mar;9(3):1041-8 PMID: 2498643
  41. 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
  42. Kinases and phosphatases in T-cell activation.
    Immunol Today. 1989 Jun;10(6):200-5 PMID: 2546570
  43. Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family.
    Cell. 1989 Sep 22;58(6):1023-4 PMID: 2550142
  44. 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
  45. Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor.
    Nature. 1990 Feb 22;343(6260):762-4 PMID: 2154701
  46. Complexity of the immediate early response of myeloid cells to terminal differentiation and growth arrest includes ICAM-1, Jun-B and histone variants.
    Oncogene. 1990 Mar;5(3):387-96 PMID: 1690380
  47. Using mini-prep plasmid DNA for sequencing double stranded templates with Sequenase.
    Biotechniques. 1988 Jun;6(6):544-6, 549 PMID: 3273187
  48. Protein tyrosine phosphorylation associated with activation of the interleukin 2 receptor.
    J Biol Chem. 1990 Apr 5;265(10):5690-4 PMID: 1690713
  49. T cell antigen receptor-mediated activation of phospholipase C requires tyrosine phosphorylation.
    Science. 1990 Mar 30;247(4950):1584-7 PMID: 2138816
  50. 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
  51. Localized cytosolic domains of the erythropoietin receptor regulate growth signaling and down-modulate responsiveness to granulocyte-macrophage colony-stimulating factor.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4801-5 PMID: 1711211
  52. 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
  53. Cloning of the gamma chain of the human IL-2 receptor.
    Science. 1992 Jul 17;257(5068):379-82 PMID: 1631559
  54. 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
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
DOI
10.1073/pnas.90.7.2719
Published
1993-04-01
Pages
2719-23
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46167
Subset
IM
Grants
NIAID NIH HHS · IT-32AI07363 · United States
NCI NIH HHS · R01 CA-17643 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.7.2719 PMC Full Text View journal details
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