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Signaling for cell growth regulation and function of heterotrimeric G protein

Research Project

Project/Area Number 06454653
Research Category

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

Allocation TypeSingle-year Grants
Research Field Functional biochemistry
Research InstitutionTOKYO INSTITUTE OF TECHNOLOGY

Principal Investigator

ITOH Hiroshi  TOKYO INST.OF TECHNOL,DEPT.BIOSCI.& BIOTECH., ASSOC.PROF., 生命理工学部・寄附講座客員助教授 (10183005)

Co-Investigator(Kenkyū-buntansha) MIZUNO Norikazu  TOKYO INST.OF TECHNOL,DEPT.BIOSCI.& BIOTECH., RES.ASSOC., 生命理工学部, 寄附講座教員 (90212232)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1995: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥5,400,000 (Direct Cost: ¥5,400,000)
KeywordsCell Growth / Signal Transduction / G Protein / MAP Kinase / βγサブユニット
Research Abstract

Heterotrimeric GTP-binding proteins (G proteins) are composed of alpha, beta, and gamma subunits, and transduce a variety of signals from seven transmembrane receptors to effector molecules. Although it was known that cell growth is regulated by the G protein-mediated signals, the molecular mechanism of the intracellular signal transduction remains unclear. In this study, we attempted to clarify the relationship of the G protein-mediated signaling and the Ras・MAP kinase cascade using transient transfection of G protein subunits into HEK 293 cells. By measuring MAP kinase activity, we found that G protein betagamma subunit function as a signal transducer in the signaling from receptors, and the betagamma subunit activates Ras. Moreover, mutation analysis suggested that the C-terminal 2 amino acids of G protein beta subunit are required for association with G protein gamma subunit, and the C-terminal region of the beta subunit participates differentially in the signaling for MAPK/ERK and JNK/SAPK activations in the cells. Further biological studies using the mutants of G protein beta subunit should throw more light on the role of G proteins in the signaling for cell growth regulation.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] A.Ito et al.: "G protein βγ subunit activates Ras,Raf,and MAP kinase in HEK 293 cells" FEBS Letters. 365. 183-187 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Yamauchi et al.: "Carboxyl Terminal of G protein β subunit is required for association with γ subunit" Biochem.Biophys.Res.Commun.214. 694-700 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Horie et al.: "Hamster α_<1B>-adrenergic receptor directly activates Gs in the transfacted CHO cells" Molecular Pharmacology. 48. 392-400 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Yamauchi et al.: "C-terminal mutation of G protein β subunit affects differentially etracellular signal-regulated kinase and c-Jun N-terminal Kinase pathways in HEK 293 cells" Journal of Biological Chemistry. 272. 7602-7607 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Edamatsu et al.: "Inducible high-level expression vector for mammalian cells,pEF-LAC carrying human elongation factor 1α promoter and lac operator" Gene. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Nishiya et al.: "Activation of Stat1 and subsequent Transcription of inducible NO synthese gene in C6 gliona cells is independent of interferm γ induced MAPK activation that is mediated by p21ras" FEBS Letters. (in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 伊東 広他: "情報変換物質:G蛋白質、広川ニューロサイエンス5" 広川書店, 166 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 伊東 広他: "脳における情報伝達" 共立出版, 412 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A.Ito, T.Satoh, Y.Kaziro, and H.Itoh: "G protein betagamma subunit activates Ras, Raf, and MAP kinase in HEK 293 cells." FEBS Lett. 365. 183-187 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Yamauchi, Y.Kaziro, and H.Itoh: "Carboxyl terminal of G protein beta subunit is required for association with gamma subunit." Biochem.Biophys.Res.Commun.214. 694-700 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Horie, H.Itoh, and G.Tsujimoto: "Hamster alpha1B-adrenergic receptor directly activates Gs in the transfected CHO cells." Mol.Pharmacol.48. 392-400 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] J.Yamauchi, Y.Kaziro, and H.Itoh: "C-terminal mutation of G protein beta subunit affects differentially extracellular signal-regulated kinase and c-Jun N-terminal kinase pathways in HEK 293 cells." J.Biol.Chem.272. 7602-7607 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Edamatsu, Y.Kaziro, and H.Itoh: "Inducible high-level expression vector for mammalian cells, pEF-LAC carrying human elongation factor 1alpha promoter and lac operator." Gene. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Nishiya, T.Uehara, H.Edamatsu, Y.Kaziro, H.Itoh, and Y.Nomura.: "Activation of Stat1 and subsequent transcription of inducible nitric oxide synthase gene in C6 glioma cells is independent of interferon-gamma-induced MAPK activation that is mediated by p21ras." FEBS lett.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] A. Ito et al.: "G protein βγ subunit activates Ras, Raf, and MAP kinase in HEK293 cells" FEBS Letters. 365. 183-187 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] J. Yamauchi et al.: "Carboxyl terminal of G protein β subunit is required for association with γ subunit" Biochem. Biophys. Res. Commun.214. 694-700 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K. Horie et al.: "Hamster α_1B-adrenergic receptor directly activates Gs in the transfected CHO cells" Mol. Pharmacol.48. 392-400 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 伊東 広: "細胞内へシグナルを伝達するGタンパク質の発見-1994年ノ-ベル医学生理学賞" 化学. 50. 96-101 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 伊東 広: "情報変換物質:Gタンパク質、広川ニューロサイエンス5" 広川書店, 166 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 伊藤 明子: "Gタンパク質βγサブユニット複合体を介するMAPキナーゼの活性化" 生化学. 66. 751 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 枝松 裕紀: "動物細胞においてLacシステムを用いた活性型GTP結合タンパク質の誘導発現と細胞増進シグナルの解析" 生化学. 66. 1067 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 平林 哲也: "ミクログリア、マクロファージによる初代培養ニューロンの細胞死" 生化学. 66. 688 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 伊東 宏: "Gタンパク質を介するシグナル伝達" 医学のあゆみ. 171. 337-342 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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