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Studies on the conformation and functions of ras-related low Mr GTP-binding proteins.

Research Project

Project/Area Number 03304052
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field 代謝生物化学
Research InstitutionGifu University

Principal Investigator

NOZAWA Yoshinori  Gifu University, School of Medicine, Biochemistry, Professor, 医学部, 教授 (10021362)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Kunihiro  Nagoya University, Faculty of Science, Molecular Biology, Professor, 理学部, 教授 (70116375)
YAMAMOTO Masayuki  University of Tokyo, Faculty of Science, Cellular Molecular Biology, Professor, 理学部, 教授 (40114706)
NARUMIYA Shuh  Kyoto University, School of Medicine, Pharmacology, Professor, 医学部, 教授 (70144350)
KATADA Toshiaki  Tokyo Institute of Technology, Department of Life Science, Professor, 生命理工学部, 教授 (10088859)
TAKAI Yoshimi  Kobe University, School of medicine, Biochemistry, Professor, 医学部, 教授 (60093514)
石橋 貞彦  広島大学, 医学部, 教授 (90012616)
関水 和久  東京大学, 薬学部, 助教授 (90126095)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1992: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1991: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsLow molecular weight / GTP-binding protein / Botulinum toxin / Yeast / Mammalian / Secretion / ADP-ribosylation / GTP結合蛋白質
Research Abstract

It is well known that a variety of ras-related low Mr GTP-binding proteins are present from yeast to mammalian. We have purified and identified several kinds of low Mr GTP-binding proteins such as rhoA, rac,ram and c25KG proteins in mammalian tissues. rhoA was identified a sole substrate of botulinum C3 enzyme in human platelet and suggested to be involved in cytoskeletal regulation. We observed that the C3 enzyme-like enzyme is present in bovine brain and partially purified it. rho protein was also observed to take part in contraction of smooth muscle although the mechanism has not been totally elucidated. rac protein was reported in phagocytes to control the superoxide-generating NADPH oxidase system which consists of at least one membrane and three cytosolic components. In yeast, SAR1 plays an essential role in intracellular protein transport and RSR1 has similar function as that of mammalian homolog, rap1.
Recently, several kinds of regulatory proteins for low Mr GTP-binding proteins have been reported. GTPase activating protein for ras p21 (ras-GAP) was first purified, identified and cloned. Thereafter, we purified GAPs for smg p21 and rho p20. GDP dissociation stimulator (GDS) and GDP dissociation inhibitor (GDI) have also been purified and identified for some low Mr GTP-bining proteins such as ras p21, smg proteins, rho p20, and smg p25A. The modes of the action of these regulatory proteins on the GTP-binding proteins were investigated and it was shown that the C-terminal prenylation such as farnesylation and geranylgeranylation is necessary for their functions.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] K.Nagata: "Characterization and site-directed mutagenesis of a low Mr GTP-binding protein,ram P25,expressed in Escheridhia coli" J.Biol.Chem.267. 19600-19606 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Hirata: "Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle." J.Biol.Chem.267. 8719-8722 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Nemoto: "A rho product in human blood platelets." J.Biol.Chem.267. 20916-20920 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Mizushima: "Inhibition of Escherichia coli DNA topoisomerase I activity by phospholipids." Biochem.J.285. 503-506 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kurokawa: "Changes in ADP-ribosylation of rho-related protein by exoenzyme C3 from Clostrdium botulinum with maturation in rat testis." Biochem.Int.27. 1067-1071 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Ozawa: "Mapping of the human GSPT1 gene,a human homologue of the yeast GST1 gene,to chromosomal band 16p13.1" Somatic Cell Mol.Genet. 18. 189-194 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Seguchi: "Brefeldin A-resistant mutants of human epidermoid carcinoma cell line with structural changes of Golgi apparatus." J.Biol.Chem.267. 11626-11630 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Tanaka: "Schizosaccharomyces pombe map3+ encodes the putative M-factor receptor." Mol.Cell.Biol.12. 1827-1834 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] R.Ruggieai: "RSR1,a ras-like gene homologous to Krev-1 (smg21A/rap1A):role in the development of cell polarity and interactions with the ras pathway in Saccharomyces cerevisiae." Mol.Cell.Biol.12. 758-766 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Oka: "Reconstitution of GTP-dependent Sarl protein in ER to Golgi transport." J.Cell Biol.114. 671-679 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Nagata: "Characterization and site-directed mutagenesis of a low Mr GTP-binding protein, ram p25, expressed in Escherichia coli" J. Biol. Chem.267. 19600-19606 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Hirata: "Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle." J. Biol. Chem.267. 8719-8722 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Takei,Y: "A GTP-binding protein in rat liver nuclei serving as the specific substrate of pertussis toxin-catalyzed ADP-ribosylation." J. Biol. Chem.267. 5085-5089 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Y.Nemoto: "A rho product in human blood platelets." J. Biol. Chem.267. 20916-20920 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Mizushima: "Inhibition of Escherichia coli DNA topoisomerase I activity by phospholipids." Biochem. J.285. 503-506 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kurokawa: "Changes in ADP-ribosylation of rho-related protein by exoenzyme C3 from Clostridium botulinum with maturation in rat testis." Biochem. Int.27. 1067-1071 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Ozawa: "Mapping of the human GSPT1 gene, a human homologue of the yeast GST1 gene, to chromosomal band 16p13.1" Somatic Cell Mol. Genet.18. 189-194 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Seguchi: "Brefeldin A-resistant mutants of human epidermoid carcinoma cell line with structural changes of the Golgi apparatus." J. Biol. Chem.267. 11626-11630 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Tanaka: "Schizosaccharomyces pombe map3+ encodes the putative M-factor receptor." Mol. Cell. Biol.12. 1827-1834 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] R.Ruggieai: "RSR1, a ras-like gene homologous to Krev-1 (smg21A/rap1A): role in the development of cell polarity and interactions with the ras pathway in Saccharomyces cerevisiae." Mol. Cell. Biol.12. 758-766 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Oka: "Reconstitution of GTP-dependent Sar1 protein in ER to Golgi transport." J. Cell Biol.114. 671-679 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Nagata: "Chracterization and site-directed mutagenesis of a low Mr GTP-binding protein,ram p25,expressed in Escherichia coli" J.Biol.Chem.267. 19600-19606 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K,Hirata: "Involvement of rho p21 in the GTP-inhanced calcium ion sensitivity of smooth muscle." J.Biol.Chem.267. 8719-8722 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Nemoto: "A rho product in human blood platelets." J.Biol.Chem.267. 20916-20920 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Mizushima: "Inhibition of Esxherichia coli DNA topoisomerase I activity by phospholipids." Biochem.J.285. 503-506 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kurokawa: "Changes in ADP-ribosylation of rho-raleted protein by exoenzyme C3 from clostridium botulinum with maturation in rat testis." Biochem.Int.27. 1067-1071 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Ozawa: "Mapping of the human GSPT1 gene,a human homologue of the yeast GST1 gene,to chromosonal band 16p13,1" Somatic Cell Mol.Genet.18. 189-194 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Seguchi: "Brefedin A-resistant mutants of human epidermoid carcioma cell line with structural changes of the Golgi apparatus." J.Biol.Chem.267. 11626-11630 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Tanaka: "Schizosaccharaomyces pombe map3 encodes the putative M-factor receptor." Mol.Cell.Biol.12. 1827-1834 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] R.Ruggieai: "RSR1,a ras-like gene homologous to Krev-1 (smg21A/raplA):role in the development of cell polarity and interactions with the ras pathway in Saccharomyces cerevisiae." Mol.Cell.Biol.12. 758-766 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Oka: "Reconstitution of GTP-dependent Sarl protein in ER to Golgi-tranpsport." J.Cell Biol.114. 671-679 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagata,K.: "Presence and some characterization of GDP dissociation inhibitors for a low Mr GTPーbinding protein,ram p25,in rat spleen cytosol." Life Sci.in press. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Takai,Y.: "Small GTPーbinding proteins." Int.Rev.Cytol.133. 187-230 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Maehama,T.: "Identification of a botulinum C3ーlike enzyme in bovine brain that catalyzes ADPーribosylation of GTPーbinding proteins." J.Biol.Chem.266. 10062-10065 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Morii,N.: "Purification of GTPaseーactivating protein specific for the rho gene products." J.Biol.Chem.266. 7646-7650 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hirai,H.: "Inhibitory action of phospholipidーinteracting drugs on transcription initiation in a nuclear extract of Ehrlich ascites tumor cells." Biochim.Biophys.Acta. 1088. 191-196 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yamashita,A.: "Reduction of mono(ADPーribosyl)ation of 20 kDa protein with maturation in rat testis:involvement of guanine nucleotides." Biochim.Biophys.Acta. 1091. 46-50 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Higuchi,M.: "TNFーmediated cytotoxicity:importance of intracellular cGMP level for determining TNFーsensitivity." Mol.Immunol.28. 1039-1044 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Misumi,Y.: "Functional expression of furin demonstrating its intracellular localization and endoprotease activity for processing of proalbumin and complement C3." J.Biol.Chem.266. 16954-16959 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Imai,Y.: "Identification of a GTPaseーactivating protein homolog in Schizosaccharomyces pombe." Mol.Cell.Biol.11. 3088-3094 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Irie,K.: "SGV1 encodes a CDC28/cdc2ーrelated kinase required for a Gα subunitーmediated adaptive response to pheromone in S.cerevisiae." Cell. 65. 785-795 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Oka,T.: "Reconstitution of GTPーbinding Sar1 protein function in ER to Golgi transport." J.Cell Biol.114. 671-679 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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