1991 Fiscal Year Annual Research Report

種々のプロティンキナ-ゼとGTP結合蛋白質による遺伝子発現の制御機構

Research Project

Project/Area Number	03680171
Research Institution	Kobe University
Principal Investigator	貝淵弘三神戸大学, 医学部, 助教授 (00169377)
Keywords	プロテインキナ-ゼ / GTP結合蛋白質 / 遺伝子発現 / ras p21 / smg GDS / cーfos
Research Abstract	本年度は遺伝子発現におけるras p21とsmg P21及びrafキナ-ゼの作用機構に関して検討を行ない、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に対するGOP/GTP交換反応促進蛋白質,smg GDS,を精製し、その全一次構造を決定している。ras p21に対するGDP/GTP交換反応制御蛋白質は現在まで同定されていなかったが、私共はsmg GDSがKiーras p21にも同様に作用することを明らかにした。また、NIH/3T3細胞にkiーras p21とsmg GDSを同時に発現させると、cーfos遺伝子の発現が促進されることを明らかにした。一方、smg p21はras p21と同じアミノ酸配列のエフェクタ-領域を持つため、ras p21の作用に拮抗、あるいは類似の作用を示すと考えられている。私共はNIH/3T3細胞を用いた実験で、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-ゼと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。ところで、Swiss 3T3細胞をPDGFで刺激するとras p21がGDP結合型からGTP結合型へと変換されること、NIH/3T3細胞にras遺伝子を発現させるとrafキナ-ゼのリン酸化が促進され活性化されることが、既に報告されている。このことと、本年度の私共の研究成果より、PDGF受容体の下流に存在するras p21がrafキナ-ゼを介してcーfos遺伝子の発現を制御していること、及びその際のras p21の活性化にsmg GDSが関与している可能性が高いことが明らかになった。今後は、ras p21がrafキナ-ゼを活性化する機構、rafキナ-ゼがcーfos遺伝子を発現制御する機構について解析を進めたいと考えている。

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 from 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 kinaseーcatalyzed 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 phosholipids." 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.Commun.182. 921-930 (1992)

1991 Fiscal Year Annual Research Report

種々のプロティンキナ-ゼとGTP結合蛋白質による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 from 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 kinaseーcatalyzed 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 phosholipids." 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.Commun.182. 921-930 (1992)

貝淵弘三神戸大学, 医学部, 助教授 (00169377)