| Project/Area Number |
13671056
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Faculty of Medicine, University of Yamanashi |
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Principal Investigator |
ASAZUMA Naoki University of Yamanashi, Faculty of Medicine, Research Associate, 医学部, 助手 (60293445)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Yukio University of Yamanashi, Faculty of Medicine, Professor, 医学部, 教授 (30134539)
SATOH Kaneo University of Yamanashi, Faculty of Medicine, Research Assistant, 医学部, 教務職員 (20242662)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Platelet / glycoprotein Ib / glycoprotein VI / von Willebrand factor / tyrosine kinase / Src family kinase / PI3-kinase / von Willebrand Factor / tyrosin kinase |
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| Research Abstract |
The interaction between immobilized von Willebrand factor (VWF) and the platelet membrane glycoprotein (GP) Ib -IX/V complex is important in platelet arrest and subsequent thrombus formation. Binding of VWF to the GPIb-IX/V complex initiates a number of intracellular signaling events that lead to platelet activation. Our recent studies revealed that the interaction by VWF-botrocetin mediates platelet activation signals in a manner similar to that of the collagen receptor, GPVI, namely through tyrosine phosphorylation of the Fc receptor γ-chain, Syk and phospholipase C γ2 (PLCγ2). We found that GPIb formed a complex with Src and PI3-kinase in resting platelets, and the amount of GPIb-associated Src increased in response to VWF and botrocetin. PI3-kinase inhibitors, wortmannin and Ly294002 had no effects on VWF-mediated platelet aggregation, as well as Src activation and tyrosine phosphorylation of the FcRγ-chain. In this study, we have also found that a portion of GPIb constitutively associates with GPVI, where they have been localized in part to glycolipid-enriched membrane domains (GEMs). Here we provide several lines of evidence that GPIb-mediated signaling pathways interacts with GPVI, and that the interaction between these two receptors is dependent on GEM-organized signaling in human platelets.
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