1990 Fiscal Year Annual Research Report

血液凝固の分子機構の研究

Research Project

Project/Area Number	02219104
Research Institution	Kyushu University
Principal Investigator	岩永貞昭九州大学, 理学部, 教授 (90029942)
Co-Investigator(Kenkyū-buntansha)	長澤滋治北海道大学, 薬学部, 助教授 (70029958) 加藤久雄国立循環器病センター, 研究所, 室長 (80029959) 森田隆司明治薬科大学, 薬学科, 教授 (90128108) 小林紀夫群馬大学, 医学部, 講師 (60008539) 松田道生自治医科大学, 血液医学研究所, 教授 (50048980)
Keywords	IX因子 / 組織因子 / β_2ー糖タンパク質 / C4b結合タンパク質 / フィブリノ-ゲン異常分子 / VII因子 / プロテインCインヒビタ- / VIII因子
Research Abstract	本年度の各班員による研究成果は以下に述べる通りである。岩永らは、IX因子FUKUOKAの第2EGF様ドメインの中にAsnー92→HIs置換を見い出し、この異常分子がVIII因子との分子間相互作用に機能的欠陥のあることを明らかにした。従って、IX因子の第2EGF様ドメインはVIII因子との結合に寄与している可能性が示唆される。加藤らは、内因系凝固の開始反応を制御する因子として、β_2ー糖タンパク質及びプロテインCインヒビタ-が主に関与することを指摘した。小林らは、組織因子(TF)の発現とその制御について検討を加え、LPS刺激によってTF活性が白血病細胞HLー60の表面上に発現するが、これはシクロヘキシルアミド(CHA)で阻害されないとした。一方、この刺激による細胞内TFの発現は、CHAによって強く制御されることを、Northern blottingを活用して証明した。ほぼ同様の結果は、中村らによる別の細胞株を用いた実験によっても支持された。長澤らは、補体系因子の1つであるC4b結合タンパク質(C4bp)とプロテインSとの分子間相互作用の実体を明らかにするとともに、C4bpの発現条件について肝由来のHepGー2株を用いて検討した。松田らは昨年に引き続いて、フィブリノ-ゲンの(Fbg)異常分子の構造解析を進め、Fbg ASAHIではγ鎖Metー310→Thr置換、Fbg KYOTO IIIではγ鎖Aspー330→Tyr置換のあることを明らかにした。また、Fbg LIMAではAα鎖のD領域にArgー141→Serの置換があり、この変異によってAsnー139が新たにNーグリコシド化されることを示唆した。森田らは、VII因子のCa^<2+>結合ドメインを調べ、この因子のN末γーGla領域に低親和性の、第1EGF様ドメインの周辺に高親和性のCa^<2+>結合部位のあることを実証した。また、VII因子のモノクロ-ナル抗体を7種作成し、この中よりVII因子とTFの相互作用を強く阻害するC6を見い出し、抗原エピト-プを決定した。さらにC6モノクロ-ナル抗体がTFとVII因子との相互作用の解析に使えるとした。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Sueyoshi T.et al.: "Cysteine Proteinase Inhibitor in the Ascitic Fluid of Sarcoma 180 Tumorーbearing Mice is a LowーMolecularーWeight Kininogen: Partial COOHーterminal Sequence and Susceptibility to Various Glandular Kallikrein." J.Biol.Chem.265. 10030-10035 (1990)
[Publications] Hase,S.et al.: "Structure of (Xyl)_2GlcーOーSerー53 Found in the First Epidermal Growth Factorーlike Domain of Bovine Blood Clotting Factor IX." J.Biol.Chem.265. 1858-1861 (1990)
[Publications] Takeya,H.et al.: "The Complete Amino Acid Sequence of the High Molecular Mass Hemorrhagic Protein HR1B,Isolated from the Venom of <Trimeresurus>___ー <flavoviridis>___ー." J.Biol.Chem.265. 16068-16073 (1990)
[Publications] Kawano,K.et al.: "Antimicrobial Peptide,Tachyplesin I,Isolated from Hemocytes of the Horseshoe Crab (<Tachypleus>___ー <tridentatus>___ー):NMR Determination of the βーsheet Structure." J.Biol.Chem.265. 15365-15367 (1990)
[Publications] Shigenaga,T.et al.: "Antimicrobial Tachyplesin Peptide Precursor: cDNA CLONING AND CELLULAR LOCALIZATION IN HORSESHOE CRAB (<Tachypleus>___ー <tridentatus>___ー)." J.Biol.Chem.265. 21350-21354 (1990)
[Publications] Takeya,H.et al.: "Primary Structure of a Hemorrhagic Metalloproteinase,HTー2,Isolated from the Venom of <Crotalus>___ー <ruber>___ー <ruber>___ー." J.Biochem.108. 711-719 (1990)
[Publications] Asakura,S.et al.: "A Monoclonal Antibody that Triggers Deacylation of an Intermediate Thrombinーantithrombin III Complex^*" J.Biol.Chem.264. 13736-13739 (1989)
[Publications] Yamazumi,K.et al.: "A γ Methionineー310 to Threonine Substitution and Consequent N__ーーGlycosylation at γ Asparagineー308 Identified in a Congenital Dysfibrinogenemia Associated with Posttraumatic Bleeding,Fibrinogen Asahi" J.Clin.Invest.83. 1590-1597 (1989)
[Publications] Asakura,S.et al.: "Hydrophobic Residues 382ー386 of Antithrombin III,AlaーAlaーAlaーSerーThr,Serve as the Epitope for an Antibody Which Facilitates Hydrolysis of the Inhibitor by Thrombin^*" J.Biol.Chem.265. 5135-5138 (1990)
[Publications] Terukina,S.et al.: "Fibrinogen Kyoto III: A Congenital Dysfibrinogen With A γ Aspartic Acidー330 to Tyrosine Substitution Manifesting Impaired Fibrin Monomer Polymerization" Blood. 74. 2681-2687 (1989)
[Publications] Takano,K.et al.: "HYPERCOAGULABILITY IN ACUTE ISCHEMIC STROKE: ANALYSIS OF THE EXTRINSIC COAGULATION REACTIONS IN PLASMA BY A HIGHLY SENSITIVE AUTOMATED METHOD" THROMBOSIS RESEARCH. 58. 481-491 (1990)
[Publications] Matsumura,Y.et al.: "Degradation pathway of kinins in tumor ascited and inhibition by kininase inhibitors: Analysis by HPLC" Agents and Actions. 29. 172-180 (1990)
[Publications] Atoda,H.et al.: "A Novel Blood Coagulation Factor IX/Factor XーBinding Protein with Anticoagulant Activity from the Venom of <Trimeresurus>___ー <flavoviridis>___ー (Habu Snake): Isolation and Characterization^1" J.Biochem.(1989)
[Publications] 官田敏行,岩永貞昭: "研究実験講座 XIII 臨床検査法の最前線II 6,凝固因子の分子異常症の検出" 中山書店(代謝27巻,第6号), 14 (1990)
[Publications] 西村仁,岩永貞昭: "臨床科学 8,内皮細胞シリ-ズ,26巻第3号" 世界保健通信社, 7 (1990)

1990 Fiscal Year Annual Research Report

血液凝固の分子機構の研究

Principal Investigator

岩永貞昭九州大学, 理学部, 教授 (90029942)

Research Products

[Publications] Sueyoshi T.et al.: "Cysteine Proteinase Inhibitor in the Ascitic Fluid of Sarcoma 180 Tumorーbearing Mice is a LowーMolecularーWeight Kininogen: Partial COOHーterminal Sequence and Susceptibility to Various Glandular Kallikrein." J.Biol.Chem.265. 10030-10035 (1990)

[Publications] Hase,S.et al.: "Structure of (Xyl)_2GlcーOーSerー53 Found in the First Epidermal Growth Factorーlike Domain of Bovine Blood Clotting Factor IX." J.Biol.Chem.265. 1858-1861 (1990)

[Publications] Takeya,H.et al.: "The Complete Amino Acid Sequence of the High Molecular Mass Hemorrhagic Protein HR1B,Isolated from the Venom of <Trimeresurus>_ー <flavoviridis>_ー." J.Biol.Chem.265. 16068-16073 (1990)

[Publications] Kawano,K.et al.: "Antimicrobial Peptide,Tachyplesin I,Isolated from Hemocytes of the Horseshoe Crab (<Tachypleus>_ー <tridentatus>_ー):NMR Determination of the βーsheet Structure." J.Biol.Chem.265. 15365-15367 (1990)

[Publications] Shigenaga,T.et al.: "Antimicrobial Tachyplesin Peptide Precursor: cDNA CLONING AND CELLULAR LOCALIZATION IN HORSESHOE CRAB (<Tachypleus>_ー <tridentatus>_ー)." J.Biol.Chem.265. 21350-21354 (1990)

[Publications] Takeya,H.et al.: "Primary Structure of a Hemorrhagic Metalloproteinase,HTー2,Isolated from the Venom of <Crotalus>_ー <ruber>_ー <ruber>___ー." J.Biochem.108. 711-719 (1990)

[Publications] Asakura,S.et al.: "A Monoclonal Antibody that Triggers Deacylation of an Intermediate Thrombinーantithrombin III Complex^*" J.Biol.Chem.264. 13736-13739 (1989)

[Publications] Yamazumi,K.et al.: "A γ Methionineー310 to Threonine Substitution and Consequent N__ーーGlycosylation at γ Asparagineー308 Identified in a Congenital Dysfibrinogenemia Associated with Posttraumatic Bleeding,Fibrinogen Asahi" J.Clin.Invest.83. 1590-1597 (1989)

[Publications] Asakura,S.et al.: "Hydrophobic Residues 382ー386 of Antithrombin III,AlaーAlaーAlaーSerーThr,Serve as the Epitope for an Antibody Which Facilitates Hydrolysis of the Inhibitor by Thrombin^*" J.Biol.Chem.265. 5135-5138 (1990)

[Publications] Terukina,S.et al.: "Fibrinogen Kyoto III: A Congenital Dysfibrinogen With A γ Aspartic Acidー330 to Tyrosine Substitution Manifesting Impaired Fibrin Monomer Polymerization" Blood. 74. 2681-2687 (1989)

[Publications] Takano,K.et al.: "HYPERCOAGULABILITY IN ACUTE ISCHEMIC STROKE: ANALYSIS OF THE EXTRINSIC COAGULATION REACTIONS IN PLASMA BY A HIGHLY SENSITIVE AUTOMATED METHOD" THROMBOSIS RESEARCH. 58. 481-491 (1990)

[Publications] Matsumura,Y.et al.: "Degradation pathway of kinins in tumor ascited and inhibition by kininase inhibitors: Analysis by HPLC" Agents and Actions. 29. 172-180 (1990)

[Publications] Atoda,H.et al.: "A Novel Blood Coagulation Factor IX/Factor XーBinding Protein with Anticoagulant Activity from the Venom of <Trimeresurus>_ー <flavoviridis>_ー (Habu Snake): Isolation and Characterization^1" J.Biochem.(1989)

[Publications] 官田敏行,岩永貞昭: "研究実験講座 XIII 臨床検査法の最前線II 6,凝固因子の分子異常症の検出" 中山書店(代謝27巻,第6号), 14 (1990)

[Publications] 西村仁,岩永貞昭: "臨床科学 8,内皮細胞シリ-ズ,26巻第3号" 世界保健通信社, 7 (1990)

1990 Fiscal Year Annual Research Report

血液凝固の分子機構の研究

Principal Investigator

岩永 貞昭 九州大学, 理学部, 教授 (90029942)

Research Products

[Publications] Sueyoshi T.et al.: "Cysteine Proteinase Inhibitor in the Ascitic Fluid of Sarcoma 180 Tumorーbearing Mice is a LowーMolecularーWeight Kininogen: Partial COOHーterminal Sequence and Susceptibility to Various Glandular Kallikrein." J.Biol.Chem.265. 10030-10035 (1990)

[Publications] Hase,S.et al.: "Structure of (Xyl)_2GlcーOーSerー53 Found in the First Epidermal Growth Factorーlike Domain of Bovine Blood Clotting Factor IX." J.Biol.Chem.265. 1858-1861 (1990)

[Publications] Takeya,H.et al.: "The Complete Amino Acid Sequence of the High Molecular Mass Hemorrhagic Protein HR1B,Isolated from the Venom of <Trimeresurus>___ー <flavoviridis>___ー." J.Biol.Chem.265. 16068-16073 (1990)

[Publications] Kawano,K.et al.: "Antimicrobial Peptide,Tachyplesin I,Isolated from Hemocytes of the Horseshoe Crab (<Tachypleus>___ー <tridentatus>___ー):NMR Determination of the βーsheet Structure." J.Biol.Chem.265. 15365-15367 (1990)

[Publications] Shigenaga,T.et al.: "Antimicrobial Tachyplesin Peptide Precursor: cDNA CLONING AND CELLULAR LOCALIZATION IN HORSESHOE CRAB (<Tachypleus>___ー <tridentatus>___ー)." J.Biol.Chem.265. 21350-21354 (1990)

[Publications] Takeya,H.et al.: "Primary Structure of a Hemorrhagic Metalloproteinase,HTー2,Isolated from the Venom of <Crotalus>___ー <ruber>___ー <ruber>___ー." J.Biochem.108. 711-719 (1990)

[Publications] Asakura,S.et al.: "A Monoclonal Antibody that Triggers Deacylation of an Intermediate Thrombinーantithrombin III Complex^*" J.Biol.Chem.264. 13736-13739 (1989)

[Publications] Yamazumi,K.et al.: "A γ Methionineー310 to Threonine Substitution and Consequent N__ーーGlycosylation at γ Asparagineー308 Identified in a Congenital Dysfibrinogenemia Associated with Posttraumatic Bleeding,Fibrinogen Asahi" J.Clin.Invest.83. 1590-1597 (1989)

[Publications] Asakura,S.et al.: "Hydrophobic Residues 382ー386 of Antithrombin III,AlaーAlaーAlaーSerーThr,Serve as the Epitope for an Antibody Which Facilitates Hydrolysis of the Inhibitor by Thrombin^*" J.Biol.Chem.265. 5135-5138 (1990)

[Publications] Terukina,S.et al.: "Fibrinogen Kyoto III: A Congenital Dysfibrinogen With A γ Aspartic Acidー330 to Tyrosine Substitution Manifesting Impaired Fibrin Monomer Polymerization" Blood. 74. 2681-2687 (1989)

[Publications] Takano,K.et al.: "HYPERCOAGULABILITY IN ACUTE ISCHEMIC STROKE: ANALYSIS OF THE EXTRINSIC COAGULATION REACTIONS IN PLASMA BY A HIGHLY SENSITIVE AUTOMATED METHOD" THROMBOSIS RESEARCH. 58. 481-491 (1990)

[Publications] Matsumura,Y.et al.: "Degradation pathway of kinins in tumor ascited and inhibition by kininase inhibitors: Analysis by HPLC" Agents and Actions. 29. 172-180 (1990)

[Publications] Atoda,H.et al.: "A Novel Blood Coagulation Factor IX/Factor XーBinding Protein with Anticoagulant Activity from the Venom of <Trimeresurus>___ー <flavoviridis>___ー (Habu Snake): Isolation and Characterization^1" J.Biochem.(1989)

[Publications] 官田 敏行,岩永 貞昭: "研究実験講座 XIII 臨床検査法の最前線II 6,凝固因子の分子異常症の検出" 中山書店(代謝27巻,第6号), 14 (1990)

[Publications] 西村 仁,岩永 貞昭: "臨床科学 8,内皮細胞シリ-ズ,26巻第3号" 世界保健通信社, 7 (1990)

岩永貞昭九州大学, 理学部, 教授 (90029942)

[Publications] Takeya,H.et al.: "The Complete Amino Acid Sequence of the High Molecular Mass Hemorrhagic Protein HR1B,Isolated from the Venom of <Trimeresurus>_ー <flavoviridis>_ー." J.Biol.Chem.265. 16068-16073 (1990)

[Publications] Kawano,K.et al.: "Antimicrobial Peptide,Tachyplesin I,Isolated from Hemocytes of the Horseshoe Crab (<Tachypleus>_ー <tridentatus>_ー):NMR Determination of the βーsheet Structure." J.Biol.Chem.265. 15365-15367 (1990)

[Publications] Shigenaga,T.et al.: "Antimicrobial Tachyplesin Peptide Precursor: cDNA CLONING AND CELLULAR LOCALIZATION IN HORSESHOE CRAB (<Tachypleus>_ー <tridentatus>_ー)." J.Biol.Chem.265. 21350-21354 (1990)

[Publications] Takeya,H.et al.: "Primary Structure of a Hemorrhagic Metalloproteinase,HTー2,Isolated from the Venom of <Crotalus>_ー <ruber>_ー <ruber>___ー." J.Biochem.108. 711-719 (1990)

[Publications] Atoda,H.et al.: "A Novel Blood Coagulation Factor IX/Factor XーBinding Protein with Anticoagulant Activity from the Venom of <Trimeresurus>_ー <flavoviridis>_ー (Habu Snake): Isolation and Characterization^1" J.Biochem.(1989)

[Publications] 官田敏行,岩永貞昭: "研究実験講座 XIII 臨床検査法の最前線II 6,凝固因子の分子異常症の検出" 中山書店(代謝27巻,第6号), 14 (1990)

[Publications] 西村仁,岩永貞昭: "臨床科学 8,内皮細胞シリ-ズ,26巻第3号" 世界保健通信社, 7 (1990)