1990 年度実績報告書

トランスメンブランコントロ-ルにおけるGTP結合蛋白質の役割

研究課題

研究課題/領域番号	02223102
研究機関	北海道大学
研究代表者	野村靖幸北海道大学, 薬学部, 教授 (00034041)
研究分担者	堅田利明東京工業大学, 理学部, 教授 (10088859) 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)
キーワード	トランスメンブランコントロ-ル / GTP結合蛋白質 / 受容性 / 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-ゼ
研究概要	GTP結合蛋白質(G蛋白質)を中心にトランスメンブランコントロ-ルの機序に関し研究し、以下の成果を得た。 1.セロトニン受容体・低分子量G蛋白質・ホスホリパ-ゼC共役系の存在(野村)、G蛋白質βγによるムスカリン受容体のアゴニスト依存性リン酸化促進効果(芳賀)、百日咳毒素感受性G蛋白質を介するアデノシンのANP依存性cGMP生成抑制,cAMP生成抑制、[Ca^<2+>]i反応増強(近藤)、プロスタグランジン受容体刺激による細胞膜Gi_2の遊離とダウンレギュレ-ション(市川)、T細胞受容体複合体・ホスホリパ-ゼC共役系にG蛋白質の関与しないこと(佐々木)、心房筋ムスカリン性受容体によるK^+チャネルへの抑制性G蛋白質各サブユニットの役割(杉本)、インスリン受容体βサブユニット遺伝子欠損による糖尿病発症(蛯名)などを示した。2.G蛋白質βγのアデニル酸シクラ-ゼ本体または34K蛋白質、Gsαへの結合による活性抑制(麻川)、抗Gi_1α,抗Gi_2α,抗Gi_3α,抗God抗体の作成とそれらによるGi_1,Gi_2,Gi_3,Goの神経系での分布(浅野)を明らかにした。3ラットNOPキナ-ゼcDNAを単離し、ヌクレオチド配列,蛋白質一次構造を示し、さらにNDPキナ-ゼは癌転移抑制因子Nm_23およびショウジョウバエ形態形成遺伝子Awdと相同蛋白質であることを示した(木村)。またNDPがG蛋白質上のGDPを直接リン酸化しGTPに変換することを明らかにした(堅田,木村)。4rho蛋白質のADPリボシル化による細胞のphenotypeの変化を見いだし(成高)、各種低分子量G蛋白質の活性制御蛋白質のGAPおよびGDI,GDSを精装し、cDNAを単離した(高井)。5.G蛋白質に対する内存性モノADPリボシル化による調節を示し(田沼)、ウシ胸腺ポリ(ADPーリボ-ス)シンテタ-ゼcDNAのクロ-ニング(上田)を行った。6.ヒトデG蛋白質(星)。酵母プロテインキナ-ゼC遺伝子(宇野,登田)の機能と機序を示した。

研究成果
(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Enomoto,Keiichi: "ADPーribosylation of Myelin basic protein by Cholera toxin." Biochimica et Biophysica Aeta. 1036. 188-192 (1990)
[文献書誌] Asano,Tomiko: "GABA_B receptors couple to G proteins G_o,G_o^* and G_<i1> but not to G_<i2>" FEBS Letters. 271. 231-235 (1990)
[文献書誌] Yatsunami,Kinio: "Effcct of tunicamycin on functions of PGE1 rcccptors from mousc mastocytoma Pー815 cells" Biochim.Biopys.Acta. 1051. 94-99
[文献書誌] Ueda,Kunihiro: "Cloning of a fullーlength cDNA encoding bovine thymus poly(ADPーribose)synthetase:evolutionarily conserved segments and their potential functions" Gene. 90. 249-254 (1990)
[文献書誌] Matsuura,Akira: "The adenylate cyclase/protein kinase cascade regulates entry into meiosis in <Saccharomyces>___ー <cerevisiae>___ー through the gene <IME1>___ー." The EMBO Journal. 9(10). 3225-3232 (1990)
[文献書誌] Shimada,F.: "Insulinーresistant diabetes associated with partial.deletion of insulinーreceptor gene" The Lancet. 335. 1179-1181 (1990)
[文献書誌] Kurachi,Yoshihisa: "Positive cooperativity in activation of the cardiac muscarinis K^+ channels by intracellular GTP" P.A.E.Journal of Physiology. 416. 216-218 (1990)
[文献書誌] Kimura,Narimichi: "Isolation and characterization of a cDNA clone enooding rat nucleoside diphosphate kinase" J.Biol.Chem. 265. 15744-15749 (1990)
[文献書誌] Okajima,Fumikazu: "Inhibition of Atrial Natriuretic Peptideーinduced cGMP Accumulation by Purinergic Agonists in FRTLー5 Thyroid Cells" Journal of Biological Chamistry. 265. (1990)
[文献書誌] HasegawaーSasaki,H.: "Mechanism of phospholipase C activation through the T cell receptor / CD3 complex" Tumor Research. 26. (1991)
[文献書誌] Hata,Yutaka: "Inhibition of the <rat>___ー p21 GTPaseーactivating proteinーstimulated GTPase activity of cーHaー<rat>___ー p21 by <smg>___ー p21 having the same putative effector domain as <ras>___ー p21s." The Journal of Biological Chemistry. 265. 7104-7107 (1990)
[文献書誌] Tanuma,Seiーichi: "Identification in human erythrocytes of mono(ADPーribosyl)protein hydrolase that cleaves a mono(ADPーribosyl)G_i linkage" FEBS Letters. 261. 381-384 (1990)
[文献書誌] Toda,Takashi: "Fissin yeast genes that confer resistance to staursporine encode an APーlーlike transcription factor and a protein kinase related to the mammalian ERKIーMAP2 and budding yeast <FVS3>___ー and <KSSI>___ー kinases" Genes & Development. (1991)
[文献書誌] Morii,N.: "Purification of GTPase activating protein specitic for the r<ho>___ー gene products" Jounal of Biological Chemistry. 266. (1991)
[文献書誌] Nakamura,F.: "Identification of two novel GTPーbinding protein αーsubunits that lack apparent ADPーribosilation site for pertussis toxin"
[文献書誌] Tadenuma,H.: "Purification and characterization of a guanineーnucleotideーbinding protein serving as the substrate of purtussin in starfish oocytes" Eur.J.Biochem.
[文献書誌] Kikkawa,Satoshi: "Conversion of GDP into GTP by nucleotide diphosphate kinase on the GTPーbinding proteins" J.Biol.Chem.265. 21536-21540 (1990)
[文献書誌] Tohda,Michihisa: "Serotonin stimulates both cytosolic and membraneーbound guanylate cyclase in NG108ー15 cells" Journal of Neurochemistry. 55. 1800-1805 (1990)
[文献書誌] Kitamura,Yoshihisa: "Effects of sulfhydrylーmodifying reagents,3ーnitroー2ーpyridinesulfenyl compounds, on the coupling between inhibitory receptors and GTPーbinding proteins G_i/G_o in rat brain membranes" Molecular Pharmacology. 38. 184-191 (1990)
[文献書誌] 野村靖幸: "脳情報伝達と加齢ー細胞・分子機序ー,蛋白質核酸酵素" 共立出版, (1991)
[文献書誌] 野村靖幸: "卵母細胞 Messenger Ribonucleic Acid発現系による脳刺激応答機構の研究,薬学雑誌" 日本薬学会, 304-314 (1990)
[文献書誌] 野村靖幸: "レセプタ-応答系の細胞内分子機構, Therapeutic Research" Life Science Publishing, (1991)

1990 年度実績報告書

トランスメンブランコントロ-ルにおけるGTP結合蛋白質の役割

研究代表者

野村靖幸北海道大学, 薬学部, 教授 (00034041)

研究成果

[文献書誌] Enomoto,Keiichi: "ADPーribosylation of Myelin basic protein by Cholera toxin." Biochimica et Biophysica Aeta. 1036. 188-192 (1990)

[文献書誌] Asano,Tomiko: "GABA_B receptors couple to G proteins G_o,G_o^* and G_<i1> but not to G_<i2>" FEBS Letters. 271. 231-235 (1990)

[文献書誌] Yatsunami,Kinio: "Effcct of tunicamycin on functions of PGE1 rcccptors from mousc mastocytoma Pー815 cells" Biochim.Biopys.Acta. 1051. 94-99

[文献書誌] Ueda,Kunihiro: "Cloning of a fullーlength cDNA encoding bovine thymus poly(ADPーribose)synthetase:evolutionarily conserved segments and their potential functions" Gene. 90. 249-254 (1990)

[文献書誌] Matsuura,Akira: "The adenylate cyclase/protein kinase cascade regulates entry into meiosis in <Saccharomyces>_ー <cerevisiae>_ー through the gene <IME1>___ー." The EMBO Journal. 9(10). 3225-3232 (1990)

[文献書誌] Shimada,F.: "Insulinーresistant diabetes associated with partial.deletion of insulinーreceptor gene" The Lancet. 335. 1179-1181 (1990)

[文献書誌] Kurachi,Yoshihisa: "Positive cooperativity in activation of the cardiac muscarinis K^+ channels by intracellular GTP" P.A.E.Journal of Physiology. 416. 216-218 (1990)

[文献書誌] Kimura,Narimichi: "Isolation and characterization of a cDNA clone enooding rat nucleoside diphosphate kinase" J.Biol.Chem. 265. 15744-15749 (1990)

[文献書誌] Okajima,Fumikazu: "Inhibition of Atrial Natriuretic Peptideーinduced cGMP Accumulation by Purinergic Agonists in FRTLー5 Thyroid Cells" Journal of Biological Chamistry. 265. (1990)

[文献書誌] HasegawaーSasaki,H.: "Mechanism of phospholipase C activation through the T cell receptor / CD3 complex" Tumor Research. 26. (1991)

[文献書誌] Hata,Yutaka: "Inhibition of the <rat>_ー p21 GTPaseーactivating proteinーstimulated GTPase activity of cーHaー<rat>_ー p21 by <smg>_ー p21 having the same putative effector domain as <ras>_ー p21s." The Journal of Biological Chemistry. 265. 7104-7107 (1990)

[文献書誌] Tanuma,Seiーichi: "Identification in human erythrocytes of mono(ADPーribosyl)protein hydrolase that cleaves a mono(ADPーribosyl)G_i linkage" FEBS Letters. 261. 381-384 (1990)

[文献書誌] Toda,Takashi: "Fissin yeast genes that confer resistance to staursporine encode an APーlーlike transcription factor and a protein kinase related to the mammalian ERKIーMAP2 and budding yeast <FVS3>_ー and <KSSI>_ー kinases" Genes & Development. (1991)

[文献書誌] Morii,N.: "Purification of GTPase activating protein specitic for the r<ho>___ー gene products" Jounal of Biological Chemistry. 266. (1991)

[文献書誌] Nakamura,F.: "Identification of two novel GTPーbinding protein αーsubunits that lack apparent ADPーribosilation site for pertussis toxin"

[文献書誌] Tadenuma,H.: "Purification and characterization of a guanineーnucleotideーbinding protein serving as the substrate of purtussin in starfish oocytes" Eur.J.Biochem.

[文献書誌] Kikkawa,Satoshi: "Conversion of GDP into GTP by nucleotide diphosphate kinase on the GTPーbinding proteins" J.Biol.Chem.265. 21536-21540 (1990)

[文献書誌] Tohda,Michihisa: "Serotonin stimulates both cytosolic and membraneーbound guanylate cyclase in NG108ー15 cells" Journal of Neurochemistry. 55. 1800-1805 (1990)

[文献書誌] Kitamura,Yoshihisa: "Effects of sulfhydrylーmodifying reagents,3ーnitroー2ーpyridinesulfenyl compounds, on the coupling between inhibitory receptors and GTPーbinding proteins G_i/G_o in rat brain membranes" Molecular Pharmacology. 38. 184-191 (1990)

[文献書誌] 野村靖幸: "脳情報伝達と加齢ー細胞・分子機序ー,蛋白質核酸酵素" 共立出版, (1991)

[文献書誌] 野村靖幸: "卵母細胞 Messenger Ribonucleic Acid発現系による脳刺激応答機構の研究,薬学雑誌" 日本薬学会, 304-314 (1990)

[文献書誌] 野村靖幸: "レセプタ-応答系の細胞内分子機構, Therapeutic Research" Life Science Publishing, (1991)

1990 年度 実績報告書

トランスメンブランコントロ-ルにおけるGTP結合蛋白質の役割

研究代表者

野村 靖幸 北海道大学, 薬学部, 教授 (00034041)

研究成果

[文献書誌] Enomoto,Keiichi: "ADPーribosylation of Myelin basic protein by Cholera toxin." Biochimica et Biophysica Aeta. 1036. 188-192 (1990)

[文献書誌] Asano,Tomiko: "GABA_B receptors couple to G proteins G_o,G_o^* and G_<i1> but not to G_<i2>" FEBS Letters. 271. 231-235 (1990)

[文献書誌] Yatsunami,Kinio: "Effcct of tunicamycin on functions of PGE1 rcccptors from mousc mastocytoma Pー815 cells" Biochim.Biopys.Acta. 1051. 94-99

[文献書誌] Ueda,Kunihiro: "Cloning of a fullーlength cDNA encoding bovine thymus poly(ADPーribose)synthetase:evolutionarily conserved segments and their potential functions" Gene. 90. 249-254 (1990)

[文献書誌] Matsuura,Akira: "The adenylate cyclase/protein kinase cascade regulates entry into meiosis in <Saccharomyces>___ー <cerevisiae>___ー through the gene <IME1>___ー." The EMBO Journal. 9(10). 3225-3232 (1990)

[文献書誌] Shimada,F.: "Insulinーresistant diabetes associated with partial.deletion of insulinーreceptor gene" The Lancet. 335. 1179-1181 (1990)

[文献書誌] Kurachi,Yoshihisa: "Positive cooperativity in activation of the cardiac muscarinis K^+ channels by intracellular GTP" P.A.E.Journal of Physiology. 416. 216-218 (1990)

[文献書誌] Kimura,Narimichi: "Isolation and characterization of a cDNA clone enooding rat nucleoside diphosphate kinase" J.Biol.Chem. 265. 15744-15749 (1990)

[文献書誌] Okajima,Fumikazu: "Inhibition of Atrial Natriuretic Peptideーinduced cGMP Accumulation by Purinergic Agonists in FRTLー5 Thyroid Cells" Journal of Biological Chamistry. 265. (1990)

[文献書誌] HasegawaーSasaki,H.: "Mechanism of phospholipase C activation through the T cell receptor / CD3 complex" Tumor Research. 26. (1991)

[文献書誌] Hata,Yutaka: "Inhibition of the <rat>___ー p21 GTPaseーactivating proteinーstimulated GTPase activity of cーHaー<rat>___ー p21 by <smg>___ー p21 having the same putative effector domain as <ras>___ー p21s." The Journal of Biological Chemistry. 265. 7104-7107 (1990)

[文献書誌] Tanuma,Seiーichi: "Identification in human erythrocytes of mono(ADPーribosyl)protein hydrolase that cleaves a mono(ADPーribosyl)G_i linkage" FEBS Letters. 261. 381-384 (1990)

[文献書誌] Toda,Takashi: "Fissin yeast genes that confer resistance to staursporine encode an APーlーlike transcription factor and a protein kinase related to the mammalian ERKIーMAP2 and budding yeast <FVS3>___ー and <KSSI>___ー kinases" Genes & Development. (1991)

[文献書誌] Morii,N.: "Purification of GTPase activating protein specitic for the r<ho>___ー gene products" Jounal of Biological Chemistry. 266. (1991)

[文献書誌] Nakamura,F.: "Identification of two novel GTPーbinding protein αーsubunits that lack apparent ADPーribosilation site for pertussis toxin"

[文献書誌] Tadenuma,H.: "Purification and characterization of a guanineーnucleotideーbinding protein serving as the substrate of purtussin in starfish oocytes" Eur.J.Biochem.

[文献書誌] Kikkawa,Satoshi: "Conversion of GDP into GTP by nucleotide diphosphate kinase on the GTPーbinding proteins" J.Biol.Chem.265. 21536-21540 (1990)

[文献書誌] Tohda,Michihisa: "Serotonin stimulates both cytosolic and membraneーbound guanylate cyclase in NG108ー15 cells" Journal of Neurochemistry. 55. 1800-1805 (1990)

[文献書誌] Kitamura,Yoshihisa: "Effects of sulfhydrylーmodifying reagents,3ーnitroー2ーpyridinesulfenyl compounds, on the coupling between inhibitory receptors and GTPーbinding proteins G_i/G_o in rat brain membranes" Molecular Pharmacology. 38. 184-191 (1990)

[文献書誌] 野村 靖幸: "脳情報伝達と加齢 ー細胞・分子機序ー,蛋白質核酸酵素" 共立出版, (1991)

[文献書誌] 野村 靖幸: "卵母細胞 Messenger Ribonucleic Acid発現系による脳刺激応答機構の研究,薬学雑誌" 日本薬学会, 304-314 (1990)

[文献書誌] 野村 靖幸: "レセプタ-応答系の細胞内分子機構, Therapeutic Research" Life Science Publishing, (1991)

1990 年度実績報告書

野村靖幸北海道大学, 薬学部, 教授 (00034041)

[文献書誌] Matsuura,Akira: "The adenylate cyclase/protein kinase cascade regulates entry into meiosis in <Saccharomyces>_ー <cerevisiae>_ー through the gene <IME1>___ー." The EMBO Journal. 9(10). 3225-3232 (1990)

[文献書誌] Hata,Yutaka: "Inhibition of the <rat>_ー p21 GTPaseーactivating proteinーstimulated GTPase activity of cーHaー<rat>_ー p21 by <smg>_ー p21 having the same putative effector domain as <ras>_ー p21s." The Journal of Biological Chemistry. 265. 7104-7107 (1990)

[文献書誌] Toda,Takashi: "Fissin yeast genes that confer resistance to staursporine encode an APーlーlike transcription factor and a protein kinase related to the mammalian ERKIーMAP2 and budding yeast <FVS3>_ー and <KSSI>_ー kinases" Genes & Development. (1991)

[文献書誌] 野村靖幸: "脳情報伝達と加齢ー細胞・分子機序ー,蛋白質核酸酵素" 共立出版, (1991)

[文献書誌] 野村靖幸: "卵母細胞 Messenger Ribonucleic Acid発現系による脳刺激応答機構の研究,薬学雑誌" 日本薬学会, 304-314 (1990)

[文献書誌] 野村靖幸: "レセプタ-応答系の細胞内分子機構, Therapeutic Research" Life Science Publishing, (1991)