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Analysis of signal transduction pathways through glycoprotein Ib in human platelets.

Research Project

Project/Area Number 11672294
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionYamanashi Medical University

Principal Investigator

SATOH Kaneo  Faculty of Medicine, Yamanashi Med. Univ., Research Assistant, 医学部, 教務職員 (20242662)

Co-Investigator(Kenkyū-buntansha) QI Roumei  Faculty of Medicine, Yamanashi Med. Univ., Assistant, 医学部, 助手 (30303423)
YATOMI Yutaka  Faculty of Medicine, Yamanashi Med. Univ., Assistant professor, 医学部, 助教授 (60200523)
OZAKI Yukio  Faculty of Medicine, Yamanashi Med. Univ., Professor, 医学部, 教授 (30134539)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsplatelet / glycoprotein Ib / von Willebrand factor / snake venom / platelet aggregation / tyrosine kinase
Research Abstract

In vivo platelet adhesion to the damaged vessel wall and subsequent platelet-platelet interaction is essential for hemostasis and thrombogenesis. The most initial step involved in this process is the interaction between the glycoprotein Ib (GPIb) and von Willebrand factor (vWF).
A number of snake venoms (botrocetin, alboaggregin-B, echicetin, Jararaca GPIb-BP, flavocetin-A) have been identified that affect the interaction between vWF and GPIb. They have proved to be valuable tools for elucidating the biological mechanism underling the GPIb-related platelet activation. In this study, we compared the effects of these GPIb-binding proteins on various parameters of platelet activation. Association of GPIb and Src, tyrosine phosphorylation of 64kDa protein, and platelet aggregation were induced by alboaggregin-B and flavocetin-A.In addition to those reactions, redistribution of Src, Lyn, and 14-3-3 to cytoskeletons and Ca^<++> influx were induced by botrocetin in the presence of vWF.However, botrocetin, in the presence of monomeric vWF, could not induced platelet aggregation, Ca^<2+> influx, and cytoskeletal association of tyrosine kinases. Echicetin or Jararaca GPIb-BP caused no reaction in these parameters.
These results suggested that tyrosine kinase might be strongly related in GPIb signal transduction(s). Since botrocetin could not induce platelet activation in the presence of monomeric vWF, the activation of platelets appear to require the clustering of GPIb by the vWF molecules with multiple binding sites.

Report

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

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Kaneo Satoh et al.: "Activation of protein-tyrosine kinase pathways in human platelets stimulated with A1 domain of von Willebrand factor."Platelets.. 11・3. 171-176 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukio Ozaki et al.: "Platelet activation mediated through membrane glycoproteins : involvement of tyrosine kinases."Seminars in thrombosis and hemostasis.. 26・1. 47-51 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneo Satoh et al.: "Activation of protein-tyrosine kinase pathways in human platelets stimulated with A1 domain of von Willebrand factor."Platelets. 11 (3). 171-176 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yukio Ozaki et al.: "Platelet activation mediated through membrane glycoproteins : involvement of tyrosine kinases."Seminars in thrombosis and hemostasis. 26 (1). 47-51 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneo Satoh: "Activation of protein-tyrosine kinase pathways in human platelets stimulated with A1 domain of von Willebrand factor."Platelets.. 11・3. 171-176 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yukio Ozaki: "Platelet activation mediated through membrane glycoproteins : involvement of tyrosine kinases."Seminars in thrombosis and hemostasis.. 26・1. 47-51 (2000)

    • Related Report
      2000 Annual Research Report

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

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