1991 Fiscal Year Annual Research Report

細胞複製と制御する細胞内情報伝達系と遺伝子発現の制御機構

Research Project

Project/Area Number	03261210
Research Institution	Kobe University
Principal Investigator	貝淵弘三神戸大学, 医学部, 助教授 (00169377)
Keywords	細胞複製 / 遺伝子発現 / cーfos / ras p21 / 低分子量G蛋白質 / Cキナ-ゼ / Aキナ-ゼ / rafキナ-ゼ
Research Abstract	本年度は細胞複製の制御におけるras p21やrafキナ-ゼの活性化機構や作用機構に焦点をあてて解折し,以下の結果を得た。私共は既にras p21類似低分子量GTP結合蛋白質,smg p21,のGDP/GTP交換反応を促進する蛋白質,smg GDSを精製してそのcDNAをクロ-ニングしている。ras p21のGDP/GTP交換反応を制御する蛋白質は現在まで同定されていなかったが,本年度,私共はsmg GDSがsmg p21のみならず,Kiーras p21にも同様に作用することを明らかにした。さらに,smg GDSがKiーras p21と共同してcーfos遺伝子を発現させると共に,NIH/3T3細胞を形質転換させることを明らかにした。一方,smg p21はras p21のエフェクタ-部位と同じアミノ酸配列を有しており,ras p21の作用に抵抗するか同様の作用を示すと推定されている。私共はsmg p21がPDGFやCキナ-ゼ,ras p21によるcーfos遺伝子発現を抑制するが,Aキナ-ゼやrafキナ-ゼによるcーfos遺伝子発現を抑制しないことを明らかにした。本年度の私共の研究成果から,ras p21のGDP/GTP交換反応を調節する蛋白質の性状が明らかになったので,今後は細胞増殖因子の受容体とras p21がsmg GDSを介してどのような機構で共役しているかについて解折をすすめたい。また,smg p21の遺伝子を用いた解折からPDGF受容体やCキナ-ゼの下流にras p21が存在し、そのエラに下流にrafキナ-ゼが存在していることがほぼ確実になった。今後はras p21がどのような標的蛋白質を介してrafキナ-ゼを活性化しているのか,rafキナ-ゼがどのようなメカニズムでcーfos遺伝子を活性化しているのかについて解折をすすめていきたい。

Research Products

(14 results)

All Other

All Publications (14 results)

[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)
[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.266. 6571-6577 (1991)
[Publications] Shirataki,H.: "Inhibition of the action of the stimulatory GDP/GTP exchange protein for smg p21 by the geranylgeranylated synthetic peptides designed from its Cーterminal region." J.Biol.Chem.266. 20672-20677 (1991)
[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.11. 1438-1447 (1991)
[Publications] Kaibuchi,K.: "Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21ーlike small GTPーbinding proteins) and characterization of stimulatory GDP/GTP exchange protein." Mol.Cell.Biol.11. 2873-2880 (1991)
[Publications] Sasaki,T.: "A mammalian inhibitory GDP/GTP exchange protein (GDP dissociation inhibitor) for smg p25A is active on the yeast SEC4 protein." Mol.Cell.Biol.11. 2909-2912 (1991)
[Publications] Mizuno,T.: "A stimulatory GDP/GTP exchange protein for smg p21 is active on the postーtranslationally processed form of cーKiーras p21 and rhoA p21." Proc.Natl.Acod.Sci.88. 6442-6446 (1991)
[Publications] Nonaka,H.: "Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for smg p25A by use of its antibody." Biochem.Biophys.Res.Commun.174. 563-556 (1991)
[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.174. 1095-1102 (1991)
[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.175. 199-206 (1991)
[Publications] Itoh,T.: "The smg GDSーinduced activation of smg p21 is initlated by cyclic AMPーdependent protein kinsecatalyzed phosphorylation of smg p21." Biochem.Biophys.Res.Commun.177. 1319-1324 (1991)
[Publications] Kawamura,S.: "Inhibition of the action of a stimulatory GDP/GTP exchange protein for smg p21 by acidic membrane phospholipids." Jpn.J.Cancer Res.82. 758-761 (1991)
[Publications] Fujioka,H.: "Transforming and cーfos promoter/enhancerーstimulating activities of a stimulatory GDP/GTP exchange protein for small GTPーbinding proteins." J.Biol.Chem.267. 926-930 (1992)
[Publications] Hiraoka,K.: "Both stimulatory and inhibitory GDP/GTP exchange proteins,smg GDS and rho GDI,are active on multiple small GTPーbinding proteins." Biochem.Biophys.Res.Commun.182. 921-930 (1992)

1991 Fiscal Year Annual Research Report

細胞複製と制御する細胞内情報伝達系と遺伝子発現の制御機構

Principal Investigator

貝淵 弘三 神戸大学, 医学部, 助教授 (00169377)

Research Products

[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)

[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.266. 6571-6577 (1991)

[Publications] Shirataki,H.: "Inhibition of the action of the stimulatory GDP/GTP exchange protein for smg p21 by the geranylgeranylated synthetic peptides designed from its Cーterminal region." J.Biol.Chem.266. 20672-20677 (1991)

[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.11. 1438-1447 (1991)

[Publications] Kaibuchi,K.: "Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for smg p21s (ras p21ーlike small GTPーbinding proteins) and characterization of stimulatory GDP/GTP exchange protein." Mol.Cell.Biol.11. 2873-2880 (1991)

[Publications] Sasaki,T.: "A mammalian inhibitory GDP/GTP exchange protein (GDP dissociation inhibitor) for smg p25A is active on the yeast SEC4 protein." Mol.Cell.Biol.11. 2909-2912 (1991)

[Publications] Mizuno,T.: "A stimulatory GDP/GTP exchange protein for smg p21 is active on the postーtranslationally processed form of cーKiーras p21 and rhoA p21." Proc.Natl.Acod.Sci.88. 6442-6446 (1991)

[Publications] Nonaka,H.: "Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for smg p25A by use of its antibody." Biochem.Biophys.Res.Commun.174. 563-556 (1991)

[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.174. 1095-1102 (1991)

[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.175. 199-206 (1991)

[Publications] Itoh,T.: "The smg GDSーinduced activation of smg p21 is initlated by cyclic AMPーdependent protein kinsecatalyzed phosphorylation of smg p21." Biochem.Biophys.Res.Commun.177. 1319-1324 (1991)

[Publications] Kawamura,S.: "Inhibition of the action of a stimulatory GDP/GTP exchange protein for smg p21 by acidic membrane phospholipids." Jpn.J.Cancer Res.82. 758-761 (1991)

[Publications] Fujioka,H.: "Transforming and cーfos promoter/enhancerーstimulating activities of a stimulatory GDP/GTP exchange protein for small GTPーbinding proteins." J.Biol.Chem.267. 926-930 (1992)

[Publications] Hiraoka,K.: "Both stimulatory and inhibitory GDP/GTP exchange proteins,smg GDS and rho GDI,are active on multiple small GTPーbinding proteins." Biochem.Biophys.Res.Commun.182. 921-930 (1992)

貝淵弘三神戸大学, 医学部, 助教授 (00169377)