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細胞内情報伝達系と細胞増殖の制御機構

Research Project

Project/Area Number 02262225
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKobe University

Principal Investigator

高井 義美  神戸大学, 医学部, 教授 (60093514)

Co-Investigator(Kenkyū-buntansha) 河田 正仁  神戸大学, 医学部, 助手 (20224785)
菊池 章  神戸大学, 医学部, 助手 (10204827)
貝淵 弘三  神戸大学, 医学部, 助教授 (00169377)
Project Period (FY) 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1990: ¥25,000,000 (Direct Cost: ¥25,000,000)
Keywordsras p21 / smg p21 / ゲラニルゲラニル基 / GDP解離促進蛋白質 / GTPase活性促進蛋白質 / Aキナ-ゼ
Research Abstract

本年度の研究において、私共はras p21類似低分子量GTP結合蛋白質の中でも、ras p21と同じエフェクタ-領域を有しているsmg p21Bに焦点をあてて解析を進めた。smg p21BのC末端のアミノ酸配列はras p21に類似してCysーAーAーXであるが、このCysにはras p21と異なり、ファルネシル基の代わりにゲラニルゲラニル基が結合していることを明らかにした。また、AーAーXの部分は取り除かれ、Cysのカルボキシル基はメチル化されていた。これらの翻訳後修飾はras p21と同様にsmg p21Bの細胞内局在と機能発現に必須であることを明らかにした。一方、私共はsmg p21のGDP/GTP交換反応を促進する蛋白質であるGDP解離促進蛋白質(GDS)を均一にまで精製し、そのcDNAをクロ-ニングして全一次構造を決定した。smg GDSはsmg p21Bの細胞膜からの解離を促進した。また、Aキナ-ゼはsmg p21Bの179番目のセリンをリン酸化するが、リン酸化されたsmg p21Bはsmg GDSとの親和性が高まることが明らかになった。私共は昨年度、smg p21のGTPase活性促進蛋白質(GAP)を部分精製した。したがって、smg p21はAキナ-ゼ、smg GDS、smg p21 GAPによりその活性が制御され、さらに細胞膜への結合も制御されることが明らかとなった。最近、ras p21がチロシンキナ-ゼの下流に位置していると報告されている。私共はsmg p21がras p21GAPを抑制することを明らかにした。したがって、smg p21の標的蛋白質の1つはras p21 GAPであり、smg p21はras p21GAPの活性を抑制することにより、チロシンキナ-ゼ系の作用を促進すると考えられる。このように、smg p21は種々の細胞内情報伝達系のクロスト-クに重要であると考えられる。以上の成績を得たことにより本年度の研究計画はほぼ達成することができた。

Report

(1 results)
  • 1990 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Fukumot,Y.: "Activation of the cーfos serumーresponse element by the activated cーHaーras protein in a manner independent of protein kinase C and cAMPーdependent protein kinase." J.Biol.Chem.265. 774-780 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sasaki,T.: "Purification and characterization from bovine brain cytosol of a protein that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A,a ras p21ーlike GTPーbinding protein." J.Biol.Chem.265. 2333-2337 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hata,Y.: "Inhibition of the ras p21 GTPaseーactivating proteinーstimulated GTPase activity of cーHaーras p21 by smg p21 having the same putative effector domain as ras p21s." J.Biol.Chem.265. 7104-7107 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ueda,T.: "Purification and characterization from bovine brain cytosol of a novel regulatory protein inhibiting the dissociation of GDP from and the subsequent binding of GTP to rhoB p20,a ras p21ーlike GTPーbinding protein." J.Biol.Chem.265. 9373-9380 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Mizoguch,A.: "Localization and subcellular distribution of smg p25A,a ras p21ーlike GTPーbinding protein,in rat brain." J.Biol.Chem.265. 11872-11879 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Araki,S.: "Regulation of reversible binding of smg p25A,a ras p21ーlike GTPーbinding protein,to synaptic plasma membranes and vesicles by its specific regulatory protein,GDP dissociation inhibitor." J.Biol.Chem.265. 13007-13015 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamamoto,T.: "Purification and characterization from bovine brain cytosol of proteins that regulate the GDP/GTP exchange reaction of smg p21s,ras p21ーlike GTPーbinding proteins." J.Biol.Chem.265. 16626-16634 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kim,S.: "Tissue and subcellular distributions of the smg 21/rapl/ Krevー1 proteins which are partly distinct from those of cーras p21s" Mol.Cell.Biol.10. 2645-2652 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matsiu,Y.: "Molecular cloning and characterization of a novel type of regulatory protein (GDI) for smg p25A,a ras p21ーlike GTPーbinding protein." Mol.Cell.Biol.10. 4116-4122 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hoshijima,M.: "Purification and characterization from bovine brain membranes of a GTPーbinding protein with a Mr of 21,000 ADPーribosylated by an ADPーribosyltransferase contaminated in botulinum toxin type C1ーidentification as the rhoA gene product." Mol.Brain.Res.7. 9-16 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yamaomo,J.: "A GTPaseーactivating protein for rhoB p20,a ras p21ーlike GTPーbinding proteinーpartial purification,characterization and subcellular distribution in rat brain." Mol.Brain.Res.8. 105-111 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sano,K.: "Differential expression of the Nーmyc,cーfos,and smg p25A genes in human neuroblastoma cells during neuronal and Schwannian differentiation." Mol.Brain.Res.9. 149-152 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kawata,M.: "Posttranslationally processed structure of the human platelet protein smg p21B:Evidence for geranylgeranylation and carboxyl methylation of the Cーterminal cysteine." Proc.Natl.Acad.Sci.USA. 87. 8960-8964 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sano,K.: "Expression of the smg p25A (a ras p21ーlike GTPーbinding protein) gene in human neuroblastoma cell lines and tumor tissues." Cancer Res.50. 7242-7245 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hori,Y.: "Activation of the serumーresponse and TPAーresponse elements by expression of the vーabl protein:comparison of the mode of action of the vーabl protein with those of protein kinase C,cyclic AMPーdependent protein kinase,and the activated cーraf protein." Oncogene. 5. 1201-1206 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Fukumoto,Y.: "Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins,ras p21ーlike small GTPーbinding proteins." Oncogene. 5. 1321-1328 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Matsui,Y.: "Molecular cloning of smg p21B and identification of smg p21 purified from bovine brain and human platelets as smg p21B." Biochem.Biophys.Res.Commun.166. 1010-1016 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Fujioka,H.: "A small GTPーbinding protein (G protein) recognized by smg p25A GDP dissociation inhibitor (GDI) in human platelet membranes and GDI for this small G protein in human platelet cytosol." Biochem.Biophys.Res.Commun.168. 1244-1252 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Isomura,M.: "Partial purification and characterization of GDP dissociation stimulator (GDS) for the rho proteins from bovine brain cytosol." Biochem.Biophys.Res.Commun.169. 652-659 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ohmori,T.: "Purification and characterization of a novel GTPーbinding protein with a M_r value of 24,000 from rat liver." Biochem.Biophys.Res.Commun.169. 816-823 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kawahara,Y.: "Identification of a major GTPーbinding protein in bovine aortic smooth muscle cytosol as the rhoA gene product." Biochem.Biophys.Res.Commun.170. 673-683 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Oku,N.: "Comparison of the mode of action of ras p21 with those of protein kinases A and C in the stimulation of gene expression in NIH/3T3 cells." FEBS.Lett.269. 148-152 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroyoshi,M.: "Role of the Cーterminal region of smg p21,a ras p21ーlike small GTPーbinding protein,in membrane and smg p21 GDP/GTP exchange protein interactions." J.Biol.Chem.266. 2962-2969 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hata,Y.: "Enhancement of the actions of smg p21 GDP/GTP exchange protein by the protein kinase Aーcatalyzed phosphorylation of smg p21." J.Biol.Chem.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Katayama,M.: "The postーtranslationally modified Cーterminal structure of bovine aortic smooth muscle rhoA p21." J.Biol.Chem.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Araki,S.: "Role of the Cーterminal region of smg p25A in its interaction with membranes and the GDP/GTP exchange protein." Mol.Cell.Biol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sasaki,T.: "A mammalian inhibitory GDP/GTP exchange protein (GDI) for smg p25A is active on the yeast SEC4 protein." Mol.Cell.Biol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kaibuchi,K.: "Molecular cloning and characterization of the stimulatory GDP/GTP exchange protein (GDS) for smg p21s,ras p21ーlike small GTPーbinding proteins." Mol.Cell.Biol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Isomura,M.: "Regulation of binding of rhoB p20 to membranes by its specific regulatory protein,GDP dissociation inhibitor." Oncogene. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hori,Y.: "Postーtranslational modifications of the Cーterminal region of the rho protein are important for its interaction with membranes and the stimulatory and inhibitory GDP/GTP exchange proteins." Oncogene. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kawata,M.: "The molecular heterogeneity of the smgー21/Krevー1/rapl proteins,a GTPーbinding protein having the same effector domain as ras p21s,in bovine aortic smooth muscle membranes." Oncogene. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ueda,T.: "Purification and characterization from rat liver cytosol of a GDP dissociation inhibitor (GDI) for liver 24KG,a ras p21ーlike GTPーbinding protein,with properties similar to those of smg p25A GDI." Biochemistry. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Motoike,T.: "Expression of smg p25A,a ras p21ーlike small GTPーbinding protein,during postnatal development of rat cerebellum." Dev.Brain Res.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kawamura,S.: "Stoichiometric interaction of smg p21 with its GDP/GTP exchange protein and its novel action to regulate the translocation of smg p21 between membrane and cytoplasm." Biochem.Biophys.Res.Commun.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shimizu,K.: "Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for the rho protein by use of its specific antibody." Biochem.Biophys.Res.Commun.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Yoshida,Y.: "A geranylgeranyltransferase for rhoA p21 distinct from the farnesyltransferase for ras p21s." Biochem.Biophys.Res.Commun.(1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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