1989 Fiscal Year Annual Research Report

トランスメンブランコントロールにおけるGTP結合蛋白質の役割

Research Project

Project/Area Number	01641001
Research Institution	Hokkaido University
Principal Investigator	野村靖幸北海道大学, 薬学部, 教授 (00034041)
Co-Investigator(Kenkyū-buntansha)	倉智嘉久東京大学, 医学部, 助手 (30142011) 櫨木修東京大学, 薬学部, 助手 (80142751) 高井義美神戸大学, 医学部, 教授 (60093514) 浅野富子愛知県心身障害者コロニー, 発達障害研究所, 室長 (70100154) 麻川武雄佐賀医科大学, 教授 (50028362)
Keywords	トランスメンブランコントロール / GTP結合蛋白質 / 受容体 / イオンチャネル / 低分子量GTP結合蛋白質 / 共役機構 / 百日咳毒素 / NDPキナーゼ
Research Abstract	トランスメンブランコントロール中心に位置するGTP結合蛋白質(G蛋白質)について研究し、得られた成果は以下のようである。 1 セロトニン受容体サブタイプとG蛋白質の共役機構に、SH基がサブタイプによって異なった関与を示し、また各G蛋白質(Gi_1、Go)との共役の特異性を検討した(野村)。ムスカリン性アセチルコリン受容体のリン酸化を示し、その機能的意義を示した(芳賀)。2 アデニル酸シクラーゼ活性への精製βγ2量体の抑制機構を再構成法により示し(麻川)また心筋細胞Kチャネル開口制御機構へのβγ2量体の関与とアラキドン酸代謝物(ロイコトリエン)の関与を示した(倉智)。3 Gi_<2α>、Gi_<3α>、Goαの精製に成功、G_2idとGodに対する抗体を調製しイムノアッセイ法を行い、Gi_2は広い組織に、一方Goは神経系組織に高く分布することを示した(浅野)。4 ウシ脳より新しい低分子量G蛋白質smgp21、smgp25を発見、精製し、それらの一次構造も決定した。またsmgp21のプロテインキナーゼAによるリン酸化、活性調節因子もみいだした(高井)。5 G蛋白質の新しい内在性活性調節因子に関し検討する中で、ボツリヌス色素の触媒するADPリボシル化反応の修飾因子を発見し、その性質の一部を明らかにした(堅田)。6 G蛋白質活性の生理的調節因子の一つとしての可能性の高いNDPキナーゼについて、Gi_5と複合体の状態で膜より可溶化し、精製を試み、さらにG蛋白質活性調節機構を提唱した(木村)。7 好中球の神体レセプター(CR3)機能に、百日咳毒素(IAP)感受性のG蛋白質の関与することを示し、その機構を一部明らかにした。上記のような成果の上に今後、1)細胞情報伝達に関与する新しいG蛋白質の発見、2)新G蛋白質を精製し本体と生理的役割、その機構、3)内因性調節因子の発見と活性調節機構、4)エフェクター共役機構を解明したい。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Nomura,Yasuyuki: "Ontogenesis of α-adrenoceptor coupling with GTP-binding proteins in the rat telencephalon." Journal of Neurochemistry. 53. 249-257 (1989)
[Publications] Nomura,Yasuyuki: "Effect of histamine on polyphosphoinositide metabolism in NG108-15 cells." Neurochemistry International. 14. 73-78 (1989)
[Publications] Asakawa,Takeo: "Activation of rat brain adenylate cyclase by proteases:involvement of distinct protein components in the activation by α-cymotrypsin and trypsin." Neurochemistry International. 12. 453-459 (1988)
[Publications] Asano,Tomiko: "Purification and identification of two pertussis-toxin sensitive GTP-binding proteins of bovine spleen." Biochemical and Biophysical Research Communications. 161. 1280-1285 (1989)
[Publications] Asano,Tomiko: "Identification of lung major GTP-binding protein as Gi_2 and its distribution in various rat tissues determined by immumoassay." Biochemistry. 28. 4749-4754 (1989)
[Publications] Katada,Toshiaki: "Activator protein supporting the botulinum ADP-ribosyltransferase reaction." Journal of Biological Chemistry. (1989)
[Publications] Kimura,Narimichi: "Characterization of 17-β-estradiol-dependent and independent somatostatin receptor subtypes in rat anterior pituitary." Journal of Biological Chemistry. 264. 7033-7040 (1989)
[Publications] Kimura,Narimichi: "Membrane-associated nucleoside diphosphate kinase from rat liver.Purification,characterization,and comparison with cytosolic enzyme." Journal of Biological Chemistry. 263. 4647-4653 (1988)
[Publications] Kurachi,Yoshihisa: "α-adrenergic activation of the muscarinic K^+ channel is mediated by arachidonic acid metabolites." Pflugers Arch. 414. 102-104 (1989)
[Publications] Kurachi,Yoshihisa: "Arachidonic acid metabolites as intracellular modulators of G protcin-gated cardiac K^+ channel." Nature. 337. 555-557 (1989)
[Publications] Takai,Yoshimi: "Phosphorylation of smg P21,a ras P21-like GTP-binding protein by cyclic AMP-dependent protein kinase in a cellfree system and in response to prostaglandin E_1 in intact human platelets." Journal of Biological Chemistry. (1989)
[Publications] Takai,Yoshimi: "Purification and characterization from bovine brain cytosol of two GTPase-activating proteins specific for smg P21,a GTP-binding protein having the same effector domain as c-ras P212s." Journal of Biological Chemistry. 264. 9133-9136 (1989)
[Publications] Haga,Tatsuya: "Agonist-dependentphosphorylation of cerebral and atrial muscarinic receptors:Blockade of the phoshporylation by GTP-binding regulatory proteins and its reversal by guanine nucleotides." Biomedical Research. 10. 293-299 (1989)
[Publications] Haga,Tatsuya: "Cerebral muscarinic acetylcholine receptors interact with three kinds of GTP-binding proteins in a reconstitution systems of purifid components." Molecular Pharmacology. 35. 286-294 (1989)
[Publications] Nomura,Yasuyuki: "The transmembrane signalling mechanism of serotonin-evoked inward current responses in Xenopus oocytes injected with rat brain mRNA.In:Physiology and Pharmacology of Transmembrane Signalling" Elsevier Science Publisher,Amsterdam, 125-133 (1989)
[Publications] 野村靖幸: "脳の細胞内情報伝達α受容体の脳における情報伝達" 医薬ジャーナル社, 11-48 (1989)

1989 Fiscal Year Annual Research Report

トランスメンブランコントロールにおけるGTP結合蛋白質の役割

Principal Investigator

野村 靖幸 北海道大学, 薬学部, 教授 (00034041)

Research Products

[Publications] Nomura,Yasuyuki: "Ontogenesis of α-adrenoceptor coupling with GTP-binding proteins in the rat telencephalon." Journal of Neurochemistry. 53. 249-257 (1989)

[Publications] Nomura,Yasuyuki: "Effect of histamine on polyphosphoinositide metabolism in NG108-15 cells." Neurochemistry International. 14. 73-78 (1989)

[Publications] Asakawa,Takeo: "Activation of rat brain adenylate cyclase by proteases:involvement of distinct protein components in the activation by α-cymotrypsin and trypsin." Neurochemistry International. 12. 453-459 (1988)

[Publications] Asano,Tomiko: "Purification and identification of two pertussis-toxin sensitive GTP-binding proteins of bovine spleen." Biochemical and Biophysical Research Communications. 161. 1280-1285 (1989)

[Publications] Asano,Tomiko: "Identification of lung major GTP-binding protein as Gi_2 and its distribution in various rat tissues determined by immumoassay." Biochemistry. 28. 4749-4754 (1989)

[Publications] Katada,Toshiaki: "Activator protein supporting the botulinum ADP-ribosyltransferase reaction." Journal of Biological Chemistry. (1989)

[Publications] Kimura,Narimichi: "Characterization of 17-β-estradiol-dependent and independent somatostatin receptor subtypes in rat anterior pituitary." Journal of Biological Chemistry. 264. 7033-7040 (1989)

[Publications] Kimura,Narimichi: "Membrane-associated nucleoside diphosphate kinase from rat liver.Purification,characterization,and comparison with cytosolic enzyme." Journal of Biological Chemistry. 263. 4647-4653 (1988)

[Publications] Kurachi,Yoshihisa: "α-adrenergic activation of the muscarinic K^+ channel is mediated by arachidonic acid metabolites." Pflugers Arch. 414. 102-104 (1989)

[Publications] Kurachi,Yoshihisa: "Arachidonic acid metabolites as intracellular modulators of G protcin-gated cardiac K^+ channel." Nature. 337. 555-557 (1989)

[Publications] Takai,Yoshimi: "Phosphorylation of smg P21,a ras P21-like GTP-binding protein by cyclic AMP-dependent protein kinase in a cellfree system and in response to prostaglandin E_1 in intact human platelets." Journal of Biological Chemistry. (1989)

[Publications] Takai,Yoshimi: "Purification and characterization from bovine brain cytosol of two GTPase-activating proteins specific for smg P21,a GTP-binding protein having the same effector domain as c-ras P212s." Journal of Biological Chemistry. 264. 9133-9136 (1989)

[Publications] Haga,Tatsuya: "Agonist-dependentphosphorylation of cerebral and atrial muscarinic receptors:Blockade of the phoshporylation by GTP-binding regulatory proteins and its reversal by guanine nucleotides." Biomedical Research. 10. 293-299 (1989)

[Publications] Haga,Tatsuya: "Cerebral muscarinic acetylcholine receptors interact with three kinds of GTP-binding proteins in a reconstitution systems of purifid components." Molecular Pharmacology. 35. 286-294 (1989)

[Publications] Nomura,Yasuyuki: "The transmembrane signalling mechanism of serotonin-evoked inward current responses in Xenopus oocytes injected with rat brain mRNA.In:Physiology and Pharmacology of Transmembrane Signalling" Elsevier Science Publisher,Amsterdam, 125-133 (1989)

[Publications] 野村靖幸: "脳の細胞内情報伝達α受容体の脳における情報伝達" 医薬ジャーナル社, 11-48 (1989)

野村靖幸北海道大学, 薬学部, 教授 (00034041)