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1998 Fiscal Year Final Research Report Summary

サイトカインによる細胞の増殖分化と細胞死のシグナル伝達

Research Project

Project/Area Number 09044264
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionInstitute of Molecular and Cellular Biosciences, The University of Tokyo

Principal Investigator

MIYAJIMA Atsushi  Institute of Molecular and Cellular Biosciences, The University of Tokyo, PROFESSOR, 分子細胞生物学研究所, 教授 (50135232)

Co-Investigator(Kenkyū-buntansha) COPELAND Neal  National Cancer Institute, USA,Senior Risearcher, 主任研究員
JENKINS Nancy  National Cancer Institute, USA,Senior Risearcher, 主任研究員
DAAR Ira  National Cancer Institute, USA.Senior Risearcher, 主任研究員
DONOVAN Peter  National Cancer Institute, USA,Senior Risearcher, 主任研究員
KINOSHITA Taisei  Institute of Molecular and Cellular Biosciences, The University of Tokyo, ASSIST, 分子細胞生物学研究所, 助手 (40301113)
HARA Takahiko  Institute of Molecular and Cellular Biosciences, The University of Tokyo, ASSOCI, 分子細胞生物学研究所, 助教授 (80280949)
Project Period (FY) 1997 – 1998
Keywordscytokine / cytokine receptors / signal transduction / apoptosis / hematopoiesis / germ cells / endothelial cells / development
Research Abstract

Survival of hematopoietic cells depends on cytokine signals and cells undergo apoptosis upon cytokine depletion. As we have already demonstrated that RAS activated by cytokine stimulation is important for prevention of cell death, we analyzed signals downstream of RAS by using RAS mutants. We found that both RAF/MAP kinase and PI3 kinase activated by RAS are involved in suppression of cell death. In the absence of cytokines, caspase-3 is activated and is involved in induction of cell death. In addition, as we previously isolated Oncostatin M (OSM) as a cytokine-inducible gene, we searched for its biological activity. OSM was found to be expressed in the AGM region and was shown to have a profound effect on the development of hematopoietic cells as well as **dothelial cells, possibly acting on their common precursor cells, hemangioblasts. Using the in vitro culture system of the AGM region, role of c-myb and AML in hematopoiesis was studied. OSM was also found to be a growth factor of developing sertoli cells. The molecular structure of the OSM receptor was elucidated by cloning of the receptor cDNA.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kinoshita, T.et al.: "Raf/MAPK-and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21Ras in IL-3 dependent hematopoietic cells" Oncogene. 15. 619-627 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohta, T.et al.: "Requirement of the caspase-3/CPP32 protease cascade for apoptotic death following cytokine deprivation in hematopoietic cells" J.Biol.Chem.272. 23111-23116 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichihara, M.et al.: "Oncostatin M and leukemia inhibitory factor do not utilize the same functional receptor in mice" Blood. 90. 165-173 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mukouyama, Y.et al.: "In vitro expansion of murine hematopoietic progenitors derived from the embryonic aorta gonad mesonephros region." immunity. 8. 105-114 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hara, T.et al.: "Distinct roles of oncostatin M and leukemia inhibitory factor for the development of germ cells and testis" Develop. Biol.201. 144-153 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, M.et al.: "Reconstitution of the functional mouse oncostatin M (OSM) receptor : molecular cloning of the mouse OSM receptor b subunit." Blood. 93. 804-815 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyajima A.et al.: "Cytokine signaling for proliferation, survival, and death in hematopoietic cells" Int. J. Hematol. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kurihara R.et al.: "Regulation of crytokine-mediated cell survival through two distinct pathways, Ras/NFIL3 (E4BP4) and Bcl-XL/Caspase-3, in murine IL-3 dependnet pro-B lymphocytes" Mol. Cell. Biol. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kinoshita, T., M.Shirouzu, A.Kamiya, K.Hashimoto, S.Yokoyama and A.Miyajima: "Raf/MAPK-and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21Ras in IL-3 dependent hematopoietic cells." Oncogene. 15. 619-627 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohta, T., T.Kinoshita, M.Naito, M.Masutani, T.Tsuruo and A.Miyajima: "Requirement of the caspase-3/CPP32 protease cascade for apoptotic death following cytokine deprivation in hematopoietic cells." J.Biol.Chem. 272. 23111-23116 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichihara, M., T.Hara, H.J.Kim, T.Murata, and A.Miyajima: "Oncostatin M and leukemia inhibitory factor do not utilize the same functional receptor in mice." Blood. 90. 165-173 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hara, T., K.Tamura, Y.Mukouyama, H.J Kim, H.Kogo, P.J.Donovan and A.Miyajima: "Distinct roles of oncostatin M and leukemia inhibitory factor for the development of germ cells and testis." Develop.Biol.201. 144-153 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mukouyama, Y., T.Hara, M.J.Xu, K.Tamura, P.J.Donovan, H.Kogo, K.Tsuji, T.Nakahata, and A.Miyajima: "In vitro expansion of murine hematopoietic progenitors derived from the embryonic aorta gonad mesonephros region." Immunity. 8. 105-114 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka M., T.Hara, N.G.Copeland, D.J.Gilbert, N.A.Jenkins, and A.Miyajima: "Reconstitution of the functional mouse oncostatin M (OSM) receptor : molecular cloning of the mouse OSM receptor b subunit." Blood. 93. 804-815 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kurihara R., T.Kinoshita, A.Miyajima, T.Sinjyo, T.Yoshihara, T.Inukai, M.Masutani, K.Ozawa, A.T.Lock, and T.Inaba: "Regulation of cytokine-mediated cell survival through two distinct pathways, Ras/NFIL3 (E4BP4) and Bcl-XL/Caspase-3, in murine IL-3 dependnet pro-B lymphocytes." Mol.Cell.Biol. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyajima A., Y.Itoh, and T.Kinoshita: "Cytokine signaling for proliferation, survival, and death in hematopoietic cells." Int.J.Hematol. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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