1990 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number	02223102
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)	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)
Keywords	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
Research Abstract	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。

Research Products

(22 results)

All Other

All Publications (22 results)

[Publications] Enomoto,Keiichi: "ADPーribosylation of Myelin basic protein by Cholera toxin." Biochimica et Biophysica Aeta. 1036. 188-192 (1990)
[Publications] 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)
[Publications] Yatsunami,Kinio: "Effcct of tunicamycin on functions of PGE1 rcccptors from mousc mastocytoma Pー815 cells" Biochim.Biopys.Acta. 1051. 94-99
[Publications] 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)
[Publications] 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)
[Publications] Shimada,F.: "Insulinーresistant diabetes associated with partial.deletion of insulinーreceptor gene" The Lancet. 335. 1179-1181 (1990)
[Publications] 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)
[Publications] Kimura,Narimichi: "Isolation and characterization of a cDNA clone enooding rat nucleoside diphosphate kinase" J.Biol.Chem. 265. 15744-15749 (1990)
[Publications] 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)
[Publications] HasegawaーSasaki,H.: "Mechanism of phospholipase C activation through the T cell receptor / CD3 complex" Tumor Research. 26. (1991)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Morii,N.: "Purification of GTPase activating protein specitic for the r<ho>___ー gene products" Jounal of Biological Chemistry. 266. (1991)
[Publications] Nakamura,F.: "Identification of two novel GTPーbinding protein αーsubunits that lack apparent ADPーribosilation site for pertussis toxin"
[Publications] 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.
[Publications] Kikkawa,Satoshi: "Conversion of GDP into GTP by nucleotide diphosphate kinase on the GTPーbinding proteins" J.Biol.Chem.265. 21536-21540 (1990)
[Publications] Tohda,Michihisa: "Serotonin stimulates both cytosolic and membraneーbound guanylate cyclase in NG108ー15 cells" Journal of Neurochemistry. 55. 1800-1805 (1990)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

野村靖幸北海道大学, 薬学部, 教授 (00034041)

Research Products

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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.

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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 Fiscal Year Annual Research Report

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

Principal Investigator

野村 靖幸 北海道大学, 薬学部, 教授 (00034041)

Research Products

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

[Publications] 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.

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

野村靖幸北海道大学, 薬学部, 教授 (00034041)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)