Platelet glycoprotein VI: its structure and function.
Glycoprotein (GP) VI is a platelet membrane protein with a molecular weight of 62 kDa that was identified as a physiological collagen receptor from studies of patients deficient in this protein. GPVI-deficient platelets lacked specifically collagen-induced aggregation and the ability to form thrombi on a collagen surface under flow conditions, suggesting that GPVI makes an indispensable contribution to collagen-induced platelet activation. On the platelet surface, GPVI is present as a complex with the Fc receptor (FcR) gamma-chain, probably composed of two GPVI molecules and one FcR gamma-chain dimer. GPVI must form such a dimeric complex to exhibit high affinity binding to collagen. The GPVI-induced activation mechanism is initiated by tyrosine phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of the FcR gamma-chain, and then this signal is transduced to many related proteins, mainly by tyrosine phosphorylation. GPVI is widely recognized as a requisite factor for the formation of platelet aggregates on a collagen surface under blood flow. However, individuals with GPVI-deficient or null platelets do not exhibit any strong bleeding tendency. Analyzing this apparent dichotomy should provide us with a more precise understanding of the mechanism of thrombus formation.
Moroi
Masaaki
M
Department of Protein Biochemistry, Institute of Life Science, Kurume University, 2432-3 Aikawa-machi, Kurume, Fukuoka 839-0861, Japan. mmoroi@lsi.kurume-u.ac.jp
Jung
Stephanie M
SM
D000818:Animals; D003094:Collagen / Q000378:metabolism; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen