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Analysis of cell proliferation by GM-CSF

Research Project

Project/Area Number 10680597
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

WATANABE Sumiko  Institute of Medical Science, Tokyo University, Department of Molecular and Developmental Biology, Research Associate, 医科学研究所, 助手 (60240735)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsCytokine / Receptor / Cell proliferation / GM-CSF / シグナル伝達
Research Abstract

GM-CSF regulates proliferation and differentiation of various hematopoietic cells. We have been analyzing signal transduction of human GM-CSF rcceptor and found that there are multiple distinct signaling pathways through human GM-CSF receptor. By using mutant receptors, we found that we can activate or inactivate certain signaling pathway. In this study, we tried to analyze signals for cell proliferation using the mutant hGM-CSF receptors which can activate proliferation without activation of MAPK cascade. We clones several genes by subtraction but we found difficulty to reveal function of these new genes since the cloning methods was non-functional. To clone and analyze genes by biochemical methods, we tried to establish in vitro reconstitution system of signaling pathway by fractionated cell lysates. We succeeded to make an in vitro system of STAT5 activation from hematopoietic cell lysate, but failed to apply this system to c-myc transcriptional induction. We cloned hGM-CSSF receptor binding proteins by pull-down analysis, and analyzed function of these cloned genes by STAT5 in vitro system.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Itoh, T., et al.: "Definition of the role of tyrosine residues of the common β subunit regulating multiple signaling pathways of GM-CSF receptor"Mol. Cell. Biol.. 18. 742-752 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita, Y., et al.: "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription"Blood. 91. 1496-1507 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato, T., et al.: "Induction of erythropoietin receptor gene and acquisition of responsiveness to EPO in the presence of stem cell factor in a human leukemic cell line HML/SE"J. Biol. Chem.. 273. 16921-16926 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yang. F-C, et al.: "hG-CSF stimulates the development of primitive multipotential progenitors of G-CSF receptor-transgenic mice, but does not affect their commitment"Blood. 92. 4632-4640 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mohi, G., et al.: "Activation and functional analysis of Jak2 in BA/F3 cells using the coumermycin/GyrB system"Mol. Biol. Cell.. 9. 3299-3308 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mukasa, R., et al.: "Core 2-containing O-glycans on CD43 are preferentially expressed in the memory subset of human CD4 T cells"Int. Immunol.. 11. 259-268 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, C-B, et al.: "Constitutive activation of JAK2 confers mIL-3-independent survival and proliferation of BA/F3 cells"J. Biol. Chem.. 274. 6342-6349 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh, T., et al.: "Differential influence of tyrosine residues of the common receptor β subunit on multiple signals induced by human GM-CSF"J. Allergy Clin. Immunol.. 103. 462-470 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yang, C-F, et al.: "Differential effects of human G-CSF and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice"Blood. 94. 950-958 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, R., et al.: "JAK2 mediates anti-apoptotic activity of GM-CSF through multiple signaling pathways with different sensitivities to kinase inhibitors"Mol. Biol. Chem.. 10. 3959-3970 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Harada, Y., et al.: "Cyclic AMP inhibits the activity of c-Jun N-terminal kinase 2 (JNK2) but not JNK1 and ERK2, in human helper T lymphocytes"Biochem. Biophys. Res. Comm.. 266. 129-134 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, R., et al.: "Signals for prevention of γ irradiation-induced apoptosis by hGM-CSF"Oncogene. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Dahl, M.E., et al.: "Association of Lyn tyrosine kinase to the GM-CSF and IL-3 receptor common βc subunit and role of Src tyrosie kinases in DNA synthesis and anti-apoptosis"Genes to Cells. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, R., et al.: "Antiapoptotic activity of the hGM-CSF receptor"J. Allergy Clin. Immunol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Watanabe, S., et al.: "Analysis of signals and functions of the chimeric hGM-CSF receptor in BA/F3 cells and transgenic mice"J. Immunol.. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh, T., Liu. R., Yokota, T., Arai, K., Watanabe, S.: "Definition of the role of tyrosine residues of the common β subunit regulating multiple signaling pathways of GM-CSF receptor."Mol. Biol.. 18. 742-752 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashita, Y., Watanabe, S., Miyazato, A., Ohya K., Ikeda U., Shimada, K., Komatsu, N., Hatake, K., Miura, Y., Ozawa, K., Mano, H.: "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription."Blood. 91. 1496-1507 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato. T, Watanabe S., Ishii, E., Tsuji, K., Nakahata, T.: "Induction of erythropoietin receptor gene and acquisition of responsiveness to erythropoietin in the presence of stem cell factor in a human leukemic cell line HML/SE."J. Biol. Chem. 273. 16921-16926 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yang, F-C., Watanabe, S., Tsuji, K., Xu, M.-J., Kaneko, A., Ebihara, Y., Nakahata, T.: "Human G-CSF stimulates the development of primitive multipotential progenitors of human G-CSF receptor-transgenic mice, but does not affect their commitment I vitro and in vivo"Blood. 92. 4632-4640 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mohi, G., Arai, K., Watanabe, S.: "Activation and functional analysis of Jak2 in BA/F3 cells using the coumermycin/GyrB system"Mol. Biol. Cell. 9. 3299-3308 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mukasa, R., Homma, T., Ohtsuki T., Hosono, O., Souta, A., Kitamura, T., Fukuda, M., Watanabe, S., Morimoto, C.: "Core 2-containin O-glycans on CD43 are preferentially expressed in the memory subset of human CD4 T cells."Int. Immunol.. 11. 259-268 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, C.-B., Itoh, T., Arai, K., Watanabe, S.: "Constitutive activation of JAK2 confers mIL-3-independent survival and proliferation of BA/F3 cells."J. Biol. Chem.. 274. 6342-6349 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh, T., Liu, R., Arai, K., Watanabe, S.: "Differential influence of tyrosine residues of the common receptor β subunit on multiple signals induced by human GM-CSF."J. Allergy Cliin. Immunol.. 103. 462-470 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yang, C.-F., Tsuji, K., Oda, A., Ebihara, Y., Xu, M.-J., Kaneko, A., Hanada, S., Mitsui, T., Kikuchi, A., Manabe, A., Watanabe, S., Ikeda, Y., Nakahata, T.: "Differential effects hG-CSF and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice."Blood. 94. 950-958 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, R., Itoh, T., Arai, K, Watanabe, S.: "JAK2 mediate anti-apoptotic activity of GM-CSF through multiple signaling pathways with different sensitivities to kinase inhibitors."Mol. Biol. Chem.. 10. 3959-3970 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Harada, Y., Miyatake, S., Arai, K., Watanabe, S.: "Cyclic AMP inhibits the activity of c-Jun N-terminal kinase 2 (JNK2) but not JNK1 and ERK2, in human helper T lymphocytes."Biochem. Biophys. Res. Comm.. 266. 129-134 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, R., Liu, C. -B., Mohi, M. G., Arai, K., Watanabe, S.: "Signals for prevention of γ irradiation-induced apoptosis by hGM-CSF."Oncogene. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Dahl, M. E., Arai, K., Watanabe, S.: "Association of Lyn tyrosine kinase to the GM-CSF and IL-3 receptor common βc subunit and role of Src tyrosie kinases in DNA synthesis and anti-apoptosis."Genes to Cell. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Liu, R., Arai, K., Watanabe, S.: "Antiapoptotic activity of the hGM-CSF receptor."J. Allergy Clin. Immunol.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Watanabe, S., Aoki, Y., Nishijima, I., Xu, M.-J., Arai, K.: "Analysis of signals and functions of the chimeric hGM-CSF receptor in BA/F3 cells and transgenic mice."J. Immunol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Itoh,T et al.: "Definition of the role of tyrosine residues of the common β subunit regulating multiple signaling pathways of GM-CSF receptor."Mol. Cell. Biol.. 18. 742-752 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamashita,Y et al.: "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription"Blood. 91. 1496-1507 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato,T et al.: "Induction of erythropoietin receptor gene and acquisition of responsiveness to EPO in the presence of stem cell factor in a human leukemic cell line HML/SE."J. Biol. Chem.. 273. 16921-16926 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yang,F-C et al.: "hG-CSF stimulates the development of primitive multipotential progenitors of G-CSF receptor-transgenic mice, but does not affect their commitment."Blood. 92. 4632-4640 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mori,G et al.: "Activation and functional analysis of Jak2 in BA/F3 cells using the coumermycin/GyrB system"Mol. Biol. Cell.. 9. 3299-3308 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mukasa,R et al.: "Core 2-containing O-glycans on CD43 are preferentially expressed in the memory subset of human CD4 T cells."Int. Immunol.. 11. 259-268 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Liu,C-B et al.: "Constitutive activation of JAK2 confers mIL-3-independent survival and proliferation of BA/F3 cells"J. Biol. Chem.. 274. 6342-6349 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Itoh,T et al.: "Differential influence of tyrosine residues of the common receptor β subunit on multiple signals induced by human GM-CSF."J. Allergy Cliin. Immunol.. 103. 462-470 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yang,C-F et al.: "Differential effects of human G-CSF and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice."Blood. 94. 950-958 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lui, R et al.: "JAK2 mediates anti-apoptotic activity of GM-CSF through multiple signaling pathways with different sensitivities to kinase inhibitors."Mol. Biol. Chem.. 10. 3959-3970 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Harada, Y et al.: "Cyclic AMP inhibits the activity of c-Jun N-terminal kinase 2 (JNK2) but not JNK1 and ERK2, in human helper T lymphocytes."Biochem. Biophys. Res. Comm.. 266. 129-134 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Liu, R et al.: "Signals for prevention of γirradiation-induced apoptosis by hGM-CSF"Oncogene. (in press). (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Dahl, M. E et al.: "Association of Lyn tyrosine kinase to the GM-CSF and IL-3 receptor common βc subunit and role of Src tyrosie kinases in DNA synthesis and anti-apoptosis."Genes to Cells. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Liu, R et al.: "Antiapoptotic activity of the hGM-CSF receptor"J. Allergy Clin. Immunol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe, S et al.: "Analysis of signals and functions of the chimeric hGM-CSF receptor in BA/F3 cells and transgenic mice"J. Immunol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamashita,Y et al: "Tec and Jak2 kinases cooperate to mediate cytokine-driven activation of c-fos transcription." Blood. 91. 1496-1507 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato,T et al: "Induction of erythropoietin receptor gene and acquisition of responsivensess to erythropoietin in the presence of stem cell factor in a human leukemic cell line HML/SE." J.Biol.Chem.273. 16921-16926 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yang,F-C et al: "Human G-CSF stimulates the development of primitive multipotential progenitors of human G-CSF receptor-transgenic mice,but does not affect their commitiment I vitro and in vivo." Blood. (in press). (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,G et al: "Activation and functional analysis of Jak2 in BA/F3 cells using the coumermycin/GyrB system." Mol.Biol.Cell.9. 3299-3308 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mukasa,R et al: "Core 2-containing O-glycans on CD43 are preferentially expressed in the memory subset of human CD4 T cells." Int.Immunol.(in press). (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Liu,C.-B et al: "Constitutive activation of JAK2 confers mIL-3-independent survival and proliferation of BA/F3 cells." J.Biol.Chem.(in press). (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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