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KMID : 1011220200060010001
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Clinical & Experimental Thrombosis and Hemostasis
2020 Volume.6 No. 1 p.1 ~ p.5
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Platelet receptor glycoprotein VI
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Park Ro-Jin
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Abstract
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Glycoprotein VI (GPVI) is a platelet surface receptor for collagen exposed to the blood following platelet adhesion via GPIb-IX-V complex-vWF interaction on damage to the endothelium. GPVI receptors form dimers on ligand binding and induces signal transduction via an immunoreceptor tyrosine-based activation motif (ITAM) located in the FcR款-chain that associates with GPVI. This eventually activates phospholipase C款2 to increase intracellular Ca2+ concentration, causing platelet activation. Cluster formation via dimerization of GPVI monomers, spatial distribution of GPVI protein on platelet membrane, and shedding of soluble GPVI fragments are important processes in regulation of GPVI and ITAM signal transduction. In many clinical and experimental studies, GPVI has been a significant target for therapeutic approaches to thrombotic diseases as patients with GPVI deficiency do not show severe bleeding tendency, and GPVI-knockout mouse models revealed an important role of GPVI in thrombus formation. As therapeutic tools targeting GPVI GPVI-Fc fusion protein, GPVI-blocking Fab fragments, anti-GPVI monoclonal antibody, and kinase inhibitors are under clinical trial. The role of GPVI shedding in platelet activation and thrombosis and hemostasis is another area of interest. In addition, recent identification of fibrin as a ligand of GPVI requires further investigations of GPVI in thrombosis and hemostasis.
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KEYWORD
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GPVI, ligand, collagen, ITAM, FcR款-chain, inflammation
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