Platelet glycoprotein VI.
Glycoprotein VI (GPVI) is a membrane glycoprotein unique to platelets and has been identified as a physiological receptor for collagen. Damage to a vessel wall exposes the subendothelial component collagen to platelets in the blood flow. Interaction of platelets with collagen via the receptor GPVI results in platelet activation and adhesion--the processes that are essential for thrombus formation. On the platelet surface, GPVI is present as a complex with the homodimeric Fc receptor y-chain (FcRgamma with a possible stoichiometry of two GPVI molecules and one FcRgamma dimer). When collagen binds to GPVI, a platelet activation cascade is initiated by tyrosine phosphorylation of the immunoreceptor tyrosine-based activation motif of FcRgamma and this phosphorylation induces the formation of a large complex composed from many signal-transducing proteins. In flow adhesion experiments that closely approximate physiological conditions, GPVI is essential for the formation of large platelet aggregates on collagen. However, GPVI-deficient patients or mice do not show any severe bleeding tendency. This suggests that a GPVI inhibitor would be able to inhibit thrombus formation but still not cause a significant bleeding tendency. Such an inhibitor would show promise as an anti-thrombotic agent for clinical use.
Jung
Stephanie M
SM
Department of Biochemistry Institute of Life Science Kurume University Kurume, Fukuoka, Japan.
Moroi
Masaaki
M
D000818:Animals; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen