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COMPARISON OF FUNCTION OF RAS FAMILY MOLECULES

Research Project

Project/Area Number 10680666
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionTokyo Institute of Technology

Principal Investigator

KOIDE Hiroshi  FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, ASSISTANT PROFESSOR, 生命理工学部, 寄附講座教員 (70260536)

Co-Investigator(Kenkyū-buntansha) KAZIRO Yoshito  FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, PROFESSOR, 生命理工学部, 寄附講座客員教授 (90012690)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOncogene / Protein / Molecular Biology / biochemistry / Signal Transduction / GTP-binding protein
Research Abstract

Ras family is a subfamily of low molecular weight GTP-binding protein and consists of Ras, R-Ras, Ral and Rap. To compare the biological roles of two highly homologous proteins, Ras and R-Ras, IL-3-dependent hematopoietic BaF3 cells and C2C12 myoblasts were utilized. R-Ras, as well as Ras, was found to suppress apoptosis of BaF3 cells upon IL-3 withdrawal. The difference between the two molecules was that activation of Ras alone was enough to inhibit apoptosis, while R-Ras required IGF-1. Further studies. revealed that the observed difference was due to the lack of ERK-activating activity in R-Ras. In the case of C2C12 cells, activation of Ras and R-Ras resulted in different phenotypes. R-Ras promoted differentiation of C2C12 cells, whereas Ras inhibited it. On the other hand, Ras was found to be involved in chemotaxis of C2C12 cells by FGF, HGF and IGF-1, while involvement of R-Ras in the chemotaxis was unlikely since activation of R-Ras was not induced by the three growth factors. Thus, the present study show that Ras and R-Ras play a similar role in survival of hematopoietic cells, but distinct roles in myogenesis.
The relation between Ras and Ral was also examined. Since RalGEF is a Ras effector, existence of the Ras > RalGEF > Ral pathway has been indicated. To examine a role of Ral in Ras-induced cellular transformation, effect of expression of Ral mutants on Ras-dependent anchorage-independent growth was investigated using human fibrosarcoma HT1080 cells. As a result, it was suggested that Ral is involved in Ras-induced anchorage-independent growth of HT1080 cells and that Ral may modulate the anchorage-independent growth through regulation of the amount of a cell cycle inhibitor, p27Kip1.

Report

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

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 鈴木 丈太郎: "Synergistic action of R-Ras and IGF-1 on Bcl-XL expression and caspase-3 inhibition in BaF3 cells"FEBS Letters. 437. 112-116 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 井上 薫: "Formation of the Ras dimer is essential for Raf-1 activation"The Journal of Biological Chemistry. 275. 3737-3740 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 鈴木 丈太郎: "Positive regulation of skeletal myogenesis by R-Ras"Oncogene. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki, J., Kaziro, Y., and Koide, H: "Synergistic action of R-Ras and IGF-1 on Bcl-xL expression and caspase-3 inhibition in BaF3 cells : R-Ras and IGF-1 control distinct anti-apoptotic kinase pathways"FEBS Lett.. 437. 112-116 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Inoue, K., Mizutani, S., Koide, H and Kaziro, Y: "Formation of the Ras Dimer is Essential for Raf-1 Activation"J. Biol. Chem.. 275. 3737-3740 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki, J., Kaziro, Y., and Koide, H: "Positive Regulation of Skeletal Myogenesis by R-Ras"Oncogene. (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] 井上薫: "Formation of the Ras dimer is essential for Raf-1 activation"The Journal of Biological Chemistry. 275. 3737-3740 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木丈太郎: "Positive regulation of skeletal myogenesis by R-Ras"Oncogene. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木丈太郎: "Synergistic action of R-Ras and IGF-1 on Bel-xL expression and caspase-3 inhibition in BaF3 cells" FEBS Letters. 437. 112-116 (1998)

    • Related Report
      1998 Annual Research Report

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

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