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Activating mechanisms of platelet GPIIb-IIIa complex by the interaction of intracellular proteins

Research Project

Project/Area Number 11671001
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

FUJIMOTO Tetsuro  School of Medicine, Hiroshima Univ., Associate Professor, 医学部, 助教授 (00221549)

Co-Investigator(Kenkyū-buntansha) SHIMOMURA Takeshi  University Hospital, Hiroshima Univ., Assistant, 医学部・附属病院, 助手 (20263741)
FUJIMURA Kingo  School of Medicine, Hiroshima Univ., Professor, 医学部, 教授 (80034114)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsplatelets / GPIIb-IIIa complex / affinity modulation / β3-endonexin / CD98 / IAP / two hybrid system / FBLP-1 / 細胞内ドメイン / フィラミン / インテグリン / GP IIb-IIIa複合体 / 情報伝達 / MAPキナーゼ / GPIIb-IIIの複合体 / affinity modulation / MAP-キナーゼ
Research Abstract

In order to determine the activating mechanisms of platelet GPIIb-IIIa complex, the role of several associated proteins was analyzed. β3-endonexin activated GPIIb-IIIa complex. However it did not effectively localize near the plasma membrane since it was a nuclear protein. CD98 activated GPIIb-IIIa complex during platelet and cell adhesion. IAP strongly activated GPIIb-IIIa complex and induced soluble ligand bindings only when it interacted with C-terminal domain of thrombospondin. Several cytoskeletal proteins including talin and filamin influenced the function of GPIIb-IIIa complex. To know these downstream pathways, proteins that bind to filamins were identified by yeast two hybrid screening. One clone was a novel cDNA, which encoded 375 amino acids and 45kDa protein. Deduced amino acid sequence showed that it contained a proline-rich domain at its N-terminal half and two LIM domains at C-terminus. We therefore, named it as FBLP-1 (Filamin Binding LIM Protein-1). Subcellular localization analysis showed that FBLP-1 co-localized with stress fibers, which stretched from focal adhesions containing GPIIb-IIIa complex. The cells, which over expressed FBLP-1, spread more effectively than the cells which did not express FBLP-1, suggesting that FBLP-1 plays a significant role on platelet adhesion. Further investigation of these associated proteins would clarify the activating mechanisms of platelet GPIIb-IIIa complex.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Fujimoto, T.T., et al.: "Involvement of Fcγ receptor polymorphism in the therapeutic response of idiopathic thrombocytoenic purpura"Br. J. Haematol.. 115. 125-130 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niiya K., et al.: "Two novel gene mutations in type I antithrombin deficiency"Int. J. Hematol.. 74. 469-472 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto, T.T., et al.: "Novel alternatively spliced form of β_3-endonexin"Thromb. Res.. 105. 63-70 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hino A., et al.: "Effects of deoxycholic acid and its epimers on lipid peroxidation in isolated rat hepatocytes"J. Biochem.. 129. 683-689 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, T., et al.: "A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenio patients"Thromb. Res.. 97. 431-440 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawano, H. et al.: "Down-regulation and redistribution of GPV/GPVf2, a subunit of von Willebrand factor receptor (GPIb/IX/V complex), on the surface membrane of thrombin-stimulated human platelets"Br. J. Haematol.. 104. 55-63 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 藤元 貴啓: "血小板産生異常と巨大血小板.細胞の形態形成の基本メカニズム"金芳堂,京都. 163-175 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto, T.T., et al.: "Involvement of Fcγ receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura."Br. J. Haematol. 115. 125-130 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niiya K., et al.: "Two novel gene mutations in type I antithrombin deficiency."Int. J. Hematol. 74. 469-472 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hino A., et al.: "Effects of deoxycholic acid and its epimers on lipid peroxidation in isolated rat hepatocytes."J. Biochem.. 129. 683-689 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kim H-G, et al.: "Hypocholesterolemic effect of bile acid sulfonate analogs in hamsters."Biol. Pharm. Bull.. 24. 218-220 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto T.T., et al.: "Novel alternatively spliced form of β_3-endonexin."Thromb. Res.. 105. 63-70 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujii, T., et al.: "A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients."Thromb. Res.. 97. 431-440 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yang W., et al.: "Two-step spreading mode of human glioma cells on fibrin monomer. Interaction of α v β 3 with the substratum followed by interaction of α5β1 with endogeneous cellular fibronectin secreted in the extracellular matrix."Thromb. Res.. 93. 279-290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawano H., et al.: "Down-regulation and redistribution of GPV/GVPf2 a subunit of von Willebrand factor receptor (GPIb/IX/V complex), on the surface membrane of thrombin-stimulated human plateles."Br. J. Haematol.. 104. 55-63 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto, T.T., et al.: "Involvement of Fcγ receptor polymorphism in the therapeutic response of idiopathic thrombocytopenic purpura"Br. J. Haematol.. 115. 125-130 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Niiya K., et al.: "Two novel gene mutations in type I antithrombin deficiency"Int. J. Hematol.. 74. 469-472 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujimoto, T.T., et al.: "Novel alternatively spliced form of β_3-endonexin."Thromb. Res.. 105. 63-70 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hino A., et al.: "Effects of deoxycholic acid and its epimers on lipid peroxidation in isolated rat hepatocytes"J. Biochem.. 129. 683-689 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kim H-G., et al.: "Hypocholesterolemic effect of bile acid sulfonate analogs in hamsters"Biol. Pharm. Bull.. 24. 218-220 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤村欣吾: "巨大血小板症候群"総合臨床. 50. 2871-2872 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 藤本 貴啓: "血小板産生異常と巨大血小板.細胞の形態形成の基本メカニズム"金芳堂, 京都. 163-175 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujii,T. et al.: "A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients."Thrombosis Research. 97. 431-440 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 坂井晃 ら: "IgG-κ型M蛋白血症を認めたMALTリンパ腫"臨床血液. 41. 658-663 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤村欣吾 ら: "Bernard-Soulier症候群"日本血栓止血学会誌. 11. 411-419 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 藤元貴啓 他: "血小板/巨核球における遺伝子発現パターンの解析"血液フロンティア. 9. 25-31 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 藤元貴啓 他: "トロンボスポンジン"血液腫瘍科. 39. 161-169 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 藤元貴啓 他: "血小板GPIIb-IIIの複合体活性化と情報伝達"血小板のダイナミズムとその制御. 19. 137-148 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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