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Characterization of receptors for human colony-stimulating factor (GM-CSF and IL-3)

Research Project

Project/Area Number 01570675
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionTokyo University

Principal Investigator

MIYAGAWA Kiyoshi (1990-1991)  Tokyo Univ., The 3rd Dept. of Int. Med., assistant professor, 医学部(病), 助手 (40200133)

宮園 浩平 (1989)  東京大学, 医学部(病)・第三内科, 助手 (90209908)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Koichi  Tokyo Univ., The 3rd Dept. of Int. Med., medical doctor, 医学部(医), 医院
TOYOSHIMA Hideo  Tokyo Univ., The 3rd Dept. of Int. Med., assistant professor, 医学部(医), 助手 (20197966)
CHIBA Shigeru  Tokyo Univ., The 3rd Dept. of Int. Med., medical doctor, 医学部(病), 医員
HIRAI Hisamaru  Tokyo Univ., The 3rd Dept. of Int. Med., associate professor, 医学部(医), 講師 (90181130)
石川 冬木  東京大学, 医学部・第三内科, 助手 (30184493)
細井 孝行  東京大学, 医学部(病)・第三内科, 医員
宮川 清  東京大学, 医学部(病)・第三内科, 医員
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Keywordscolony-stimulating factor / IL-3 / GM-CSF / soluble receptor / 分泌型受容体 / 造血因子 / インタ-ロイキン3 / 受容体 / GM-CSF
Research Abstract

GM-CSF and EL-3 can act on a broad range of hematopoietic cells and support their growth and differentiation. Although their biological role is striking, little is known about the molecular mechanism of their intracellular signaling pathway. In this study, we have demonstrated that high affinity-binding site of GM-CSF is partially blocked by the addition of IL-3.
We have also shown that low affinity receptor for GM-CSF is expressed not only in hematopoietic cells but also in a human choriocarcinoma line. Furthen-nore, addition of GM-CSF to this cell line could induce the production of gonadotropin. Therefore, 1E is likely that low affinity receptor for GM-CSF itself can transduce some signals.
Recently, soluble type of receptors has been identified for many lymphokines. These soluble receptors are presumed to have significant biological role, such as competitive inhibitor of membrane receptor. We. could reveal that there is a soluble type of GMCSF receptor. A soluble protein of 62 kDa in the supernatant of a human choriocarcinoma cell line was shown to bind to ^<125>I-labeled GM-CSF. This binding was specifically blocked by the excess addition of non-labeled GM-CSF. We could not recognize this type of receptor in the supernatant of hematopoietic cells.
The structure and the biological role of this soluble GM-CSF receptor is currently under investigation.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Sugimoto,K: "Mutations of the p53 gene in lymphoid leukemia." Blood. 77. 1153-1156 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanaka,T.: "Stimulatory effects of granulocyte colony-stimulating factor on CFU-S differentiation and pre-CFU-S proliferation in mice." Blood. 77. 2597-2602 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hirai,H.: "Analysis of Ph1-positive leukemia by PCR." Jpn.Clinical Hematol.32. 319-326 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Chiba,S.: "Establishment and erythroid differentiation of a cytokine dependent human leukemic cell line F-36." Blood. 78. 2261-2268 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugimoto,K.: "Frequent mutations in the p53 gene in human myeloid leukemia cell lines." Blood.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taketazu,F.: "IL-3 specifically inhibits GM-CSF binding to thehigher affinity receptor." J.Cell.Physiol.146. 251-257 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hanazono,Y.: "Myelodysplastic syndrome and cytokines" Elsevier Science Publishers, 10 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taketazu,F.: "Myelodysplastic syndrome and cytokines" Elsevier Science Publishers, 10 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugimoto, K., Toyoshima, H., Sakai, R., Miyagawa, K., Hagiwara, K., Hirai, H., Ishikawa, F., Takaku, F.: "Mutations of the p53 gene in lymphoid leukemia." Blood. 77. 1153-1156 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanaka, T., Suda, T., Suda, J., Inoue, T., Hirabayashi, Y., Hirai, H., Takaku, F., Miura, Y.: "Stimulatory effects of granulocyte colony -stimulating factor on CFU-S differentiation and pre-CFU-S proliferation in mice." Blood. 77. 2597-2602 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hirai, H., Ishikawa, F.: "Analysis of Phl-positive leukemia by PCR." Jpn. Clinical Hematol.32. 319-326 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Chiba, S., Takaku, F., Tange, T., Shibuya., K., Misawa, C., Sasaki, K., Miyagawa, K., Yazaki, Y., Hirai, H.: "Establishment and erythroid differentiation of a cytokine-dependent human leukemic cell line F-36 : A parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3, and a subline requiring erythropoietin." Blood. 78. 2261-2268 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugimoto, K., Toyoshima, H., Sakai, R., Miyagawa, K., Hagiwara, K., Ishikawa, F., Takaku F., Yazaki, Y., Hirai, H.: "Frequent mutations in the p53 gene in human myeloid leukemia cell lines." Blood.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hanazono, Y., Miyazono, K., Piao, Y-F., Taketazu, F., Chiba, S., Miyagawa, K., Hirai, H., Sakamoto, S., Miura, Y., Takaku, F.: Int. Hematol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Wu, H-K., Hirai, H., Inamori, K., Kitamura, K., Takaku, F.: "Anti-tumor effects of interleukin-4 and interleukin-5 against mouse B-cell lymphoma and possible mechanism of their action." Jpn. J. Cancer Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sasaki K., Chiba, S., Mano, H., Yazaki, Y., Hirai, H.: "Identification of a soluble GM-CSF binding protein in the supernatant of a human choriocarcinoma cell line." Biochem. Biophys. Res.Commun.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hanazono, Y., Miyazono, K., Tsuchimochi, H., Yamaoki, K., Miyagawa, K., Yazaki, Y., Takaku, F.: "Treatment of infective endocarditis with granulocyte colony-stimulating factor." Jap. J. Med.30. 593-596 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taketazu, F., Chiba, S., Shibuya, K., Kuwaki, T., Tsumura, H., Miyazono, K., Miyagawa, K., Takaku, F.: "IL-3 specifically inhibits GM-CSF binding to the higher affinity receptor." J. Cell. Physiol.146. 251-257 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sugimoto,K: "Mutations of the p53 gene in lymphoid leukeia." Blood. 77. 1153-1156 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanaka,T.: "Stimulatory effects of granulocyte colonyーstimulating factor on CFUーS differentiation and preーCFUーS proliferation in mice." Blood. 77. 2597-2602 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hirai,H.: "Analysis of Ph1ーpositive leukemia by PCR." Jpn.Clinical Hematol.32. 319-326 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Chiba,S.: "Establishment and erythroid differentiation of a cytokine dependent human leukemic cell line Fー36." Blood. 78. 2261-2268 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sugimoto,K.: "Frequet mutations in the p53 gene in human myloid leukemia cell lines." Blood.

    • Related Report
      1991 Annual Research Report
  • [Publications] Taketazu,F.: "ILー3 specifically inhibits GMーCSF binding to thehigher affinity receptor." J.Cell.Physiol.146. 251-257 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hanazono,Y.: "Myelodysplastic syndrome and cytokines" Elsevier Science Publishers, 10 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Taketazu,F.: "Myelodysplastic syndrome and cytokines" Elsevier Science Publishers, 10 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] S.Chiba,K.Shibuya,K.Miyagawa et al.: "Identification and cellular distribution of distinct proteins forming human GMーCSF receptor" Cell Regulation. 1. 327-335 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Miyagawa,S.Chiba,K.Shibuya et al.: "Frequent Expression of Receptors for GranulocyteーMacrophage ColonyーStimulating Factor on Human Nonhematopoietic.Tumor Cell Lines" J.Cell.Physiol.143. 483-487 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Chiba,K.Shibuya K.Miyazono,A.Tojo,K.Miyagawa et al.: "Affinity Purification of Human GranulocyteーMacrophage Colonyーstimulating FactorーChain" J.Biol.Chem.265. 19777-19781 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] F.Taketazu,S.Chiba K.Miyagawa et al.: "ILー3 Specifically Inhibits GMーCSF Binding to the Higher Affinity Receptor" J.Cell Physiol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.kuwaki,T.Kitamura,K.Miyazono,F.Takaku et al: "Characterization of human interleukin 3 receptors on a multifactor dependent cell line" Biochemical and Biophysical Research Communication. 161. 16-12 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Y.-F.Piao,S.Chiba,K.Miyazono,F.Takaku et al.: "Binding properties and proliferative effects of human recombinant granulocyte-macrophage colony stimulating factor in primary,leukemia and lymphoma" Japanese Journal of Cancer Research. 80. 887-894 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Miyagawa,S.Chiba,K.Miyazono,et al.: "Frequent expression of receptors for granulocyte-macrophage colony-stimulating factors on human solid tumor cell lines" J.Cellular Physiology.

    • Related Report
      1989 Annual Research Report
  • [Publications] K.Shibuya,S.Chiba,K.Miyazono,F.Takaku,et al.: "Effects of ubenimex on proliferation and differentiation of human bone marrow cells and leukemic cell lines,and the possible mechanisms of its action." Experimental Hematology Today. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] S.Chiba,Tojo,A.,K.Miyazono,F.Takaku et al.: "Characterization and molecular features of the cell surface receptor for human granulocyte-macrophage colony-stumulting factor." Leukemia. (1990)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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