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Analysis of signal transduction mediated by the cytokine receptor(s)

Research Project

Project/Area Number 03670251
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

MINAMI Yasuhiro  Osaka University,Institute for Molecular & Cellular Biology Research Associate, 細胞生体工学センター, 助手 (70229772)

Co-Investigator(Kenkyū-buntansha) HARADA Hisashi  Osaka University, Institute for Molecular & Cellular Biology Research Associate, 細胞生体工学センター, 助手 (10222233)
TANAKA Nobuyuki  Osaka University, Institute for Molecular & Cellular Biology Research Associate, 細胞生体工学センター, 助手 (80222115)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
KeywordsInterleukin-2(IL-2) / Interleukin-2(IL-2R) / Interleukin-2 receptor beta chain(IL-2Rbeta) / intracellular signal transduction / src-family tyrosine kinase(lck, fyn, etc) / tyrosine kinase activation / target gene / nuclear proto-oncogenes(c-fos / c-jun and c / myc genes) / c-jun and c-myc gencs) / サイトカイン / サイトカイン受容体 / チロシンキナ-ゼ / 細胞増殖 / 核内プロトオンコジ-ン / 遺伝子発現誘導 / serum responsive element(SRE)
Research Abstract

IL-2Rbeta is a critical subunit required for the intracellular signal transduction induced by IL-2 and contains the two functional cytoplasmic subregions( the "serine-rich" and the "acidic" regions), rich in serine residues and in acidic amino acids, respectively. The "acidic" region of IL-2Rbeta is a primarily important site required for associating with a src-family protein tyrosine kinase(PTK), p56^<lck>. Our recent study shows that the association between IL-2Rbeta and p56^<lck> is critical for the IL-2-induced activation of lck PTK. In addition, it was shown that another cytoplasmic region, the "serine-rich" region of IL-2Rbeta, is also required for activating lck PTK. We have also shown that another src-family PTK,fyn PTK can associate with IL-2Rbeta and is activated following IL-2 stimulation of BAF-BO3 cells where expression of lck PTK is not detectable. Futhermore, our recent collaborative study with Dr. Satoh et al. (DNAX Research Institute, USA) has in dicated that IL-2 stimulation induces the activation of the ras protein, presumably mediated by a src-family PTK(s). Interestingly, the IL-2-induced activation of a src-family PTK(s)(as well as the IL-2-induced activation of the ras protein) leads to the induction of the c-fos and c-jun genes. On the other hand, it was shown that an as yet unknown signal(s), mediated by the "serine-rich" region of IL-2Rbeta, leads to the c-myc gene induction. Thus, it became evident that IL-2Rbeta is linked to at least two distinct intracellular signaling path ways, leading to the induction of the two different sets of nuclear proto-oncogenes(c-fos/c-jun and c-myc genes).

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report

Research Products

(23 results)

All Other

All Publications (23 results)

  • [Publications] MINAMI,Y: "The Interleukin-2 receptors:insights into a complex signalling mechanism." Biochimica et Biophysica Acta. 1114. 163-177 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] SATOH,T: "Interleukin2-induced activation of ras requires two domains of Interleukin2 receptor β subunit,the essential region for growth stimulation and lck binding." J.Biol.Chem.267. 25423-25427 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] MINAMI,Y.: "Association of^p56_<lck> with IL-2receptor β chain is critical for the IL-2-induced a ctivation of ^p56_<lck>." EMBO J.12. 759-768 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] MINAMI,Y.: "The IL-2 receptor complex:Its structure,and target genes." Ammu.Rev.Immunol.11. 245-267 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] UMEHARA,H.: "Signal transduction via phospliorylated adhesion molecule,LFA-1B(CD18),is increased by culture of natural killer cellswith IL-2 in the generation of Iymphokine-Activnted killer cells." Int.Immunol.5. 19-27 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] KOBAYASHI,N.: "Functional coupling of the src-family protein tyrosine kinases,^p59_<fyn> and ^p53/56_<fyn> with the interleukin-2 receptor;implications for redundancy and pleiotropism in cytokine signnl trnnsduction." Proc.Natl.Acad.Sci.USA. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Minami, Y., Kono, T., et al: "The Interleukin-2 receptors: insights into a complex signalling mechanism" Biochimica et Biophysica Acta. 1114. 163-177 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Satoh, T., Minami, Y., et al: "Interleukin2-induced activation of ras requires two domains of Interleukin2 receptor beta subunit, the essential region for growth stimulation and lck binding" J. Biol. Chem. 267. 25423-25427 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Minami, Y., Kono, T., et al: "Association of p56^<lck> with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56^<lck>" EMBO J. 12. 759-768 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Minami, Y., Kono, T., et al: "The IL-2 receptor complex: Its structure, function, and target genes" Annu. Rev. Immunol. 11. 245-267 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Umehara, H., Takashima, A., Minami, Y., et al: "Signal transduction via phosphorylated adhesion molecule, LFA-1B(CD18), is increased by culture of natural killer cells with IL-2 in the generation of lymphokine-activated killer cells" Int. Immunol. 5. 19-27 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kobayashi, N., Kono, T., Hatakeyama, M., Minami, Y., et al: "Functional coupling of the src- family protein tyrosine kinases,, p59^<lyn> and p53/56^<lyn> with the interleukin-2 receptor;implications for redundancy and pleiotropism in cytokine signal transduction" Proc. Natl. Acad. Sci. USA. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Minami,Y.: "The Interleukin-2 receptors:insights into a complex signalling mechanism." Biochimica et Biophysica Acta. 1114. 163-177 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Satoh,T.: "Interleukin2-induced activation of ras requires two domains of Interleukin2 receptor β subunit,the essential region for growth stimulation and lck binding." J.Biol.Chem.267. 25423-25427 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Minami,Y.: "Association of p56^<lck> with IL-2 receptor β chain is critical for the IL-2-induced activation of p56^<lck>." EMBO J.12. 759-768 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Minami,Y.: "The IL-2 receptor complex:Its structure,function,and target genes." Annu.Rev.Immunol.11. 245-267 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Umehara,H.: "Signal transduction via phosphorylated adhesion molecule,LFA-1B(CD18),is increased by culture of natural killer cells with IL-2 in the generation of lymphokine-activated killer cells." Int.Immunol.5. 19-27 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kobayashi,N.: "Functional coupling of the src-family protein tyrosine kinases,p59^<lyn> and p53/56^<lyn> with the interleukin-2 receptor;implications for redundancy and pleiotropism in cytokine signal transduction." Proc.Natl.Acad.Sci.USA. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Hatakeyama: "Interaction of the ILー2 Receptor with the srcーFamily Kirase p56^<lck>:identification of Novel Intermolecular Association." Science. 252. 1523-1528 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Miyazaki: "The integrity of the conserved“WS motif"common to ILー2 and other cytokine receptors is essential for ligand birding and signal transduction." EMBO J.10. 3191-3197 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.Hatakeyama: "cーfos Gene Induction by ILー2:Identification of the Critical Cytoplasmic Regions within the ILー2 Receptor B Chain." Proc.Natl.Acad.Sci.,U.S.A.(1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Y.Mirami: "p56^<lck> associated with the ILー2 Receptor B chain is a critical element in the tyrosine kinase pathway following ILー2 stimulation."

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Taniguchi: "Drug Resistances as A Biochemical Target in Cancer Chemotherapy" Academic Press,Inc., 12 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-03-31   Modified: 2016-04-21  

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