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Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Glycoprotein VI Is a Major Collagen Receptor for Platelet Activation: It Recognizes the Platelet-Activating Quaternary Structure of Collagen, Whereas CD36, Glycoprotein IIb/IIIa, and von Willebrand Factor Do Not Beate Kehrel, Sonja Wierwille, Kenneth J. Clemetson, Olaf Anders, Michael Steiner, C. Graham Knight, Richard W. Farndale, Minoru Okuma, and Michael J. Barnes From the Department of Internal Medicine A, University of Münster, Münster, Germany; the Theodor Kocher Institute, University of Berne, Berne, Switzerland; the University Department of Internal Medicine and Pathobiochemistry, University of Rostock, Rostock, Germany; the Strangeways Research Laboratory, Cambridge, UK; the Department of Biochemistry, University of Cambridge, Cambridge, UK; and the Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Simple collagen-related peptides (CRPs) containing a repeat Gly-Pro-Hyp sequence are highly potent platelet agonists. Like collagen, they must exhibit tertiary (triple-helical) and quaternary (polymeric) structure to activate platelets. Platelet signaling events induced by the peptides are the same as most of those induced by collagen. The peptides do not recognize the 21 integrin. To identify the signaling receptor involved, we have evaluated the response to the CRP, Gly-Lys-Hyp(Gly-Pro-Hyp)10-Gly-Lys-Hyp-Gly of platelets with defined functional deficiencies. These studies exclude a primary recognition role for CD36, von Willebrand factor (vWF), or glycoprotein (GP) IIb/IIIa. Thus, both CD36 and vWF-deficient platelets exhibited normal aggregation, normal fibrinogen binding, and normal expression of CD62 and CD63, measured by flow cytometry, in response to the peptide, and there was normal expression of CD62 and CD63 on thrombasthenic platelets. In contrast, GPVI-deficient platelets were totally unresponsive to the peptide, indicating that this receptor recognizes the Gly-Pro-Hyp sequence in collagen. GPVI-deficient platelets showed some fibrinogen binding in response to collagen but failed to aggregate and to express CD62 and CD63. Collagen, but not CRP-XL, contains binding sites for 21. Therefore, it is possible that collagen still induces some signaling via 21, leading to activation of GPIIb/IIIa. Our findings are consistent with a two-site, two-step model of collagen interaction with platelets involving recognition of specific sequences in collagen by an adhesive receptor such as 21 to arrest platelets under flow and subsequent recognition of another specific collagen sequence by an activatory receptor, namely GPVI. Blood, Vol. 91 No. 2 (January 15), 1998: pp. 491-499 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. E. Jarvis, N. Raynal, J. P. Langford, D. J. Onley, A. Andrews, P. A. Smethurst, and R. W. Farndale Identification of a major GpVI-binding locus in human type III collagen Blood, May 15, 2008; 111(10): 4986 - 4996. [Abstract] [Full Text] [PDF] D. Varga-Szabo, I. Pleines, and B. 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Zirngibl Long-term Antithrombotic Protection by In Vivo Depletion of Platelet Glycoprotein VI in Mice J. Exp. Med., February 12, 2001; 193(4): 459 - 470. [Abstract] [Full Text] [PDF] D. Dormann, K. J. Clemetson, and B. E. Kehrel The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity Blood, October 1, 2000; 96(7): 2469 - 2478. [Abstract] [Full Text] [PDF] J. Hartleib, N. Kohler, R. B. Dickinson, G. S. Chhatwal, J. J. Sixma, O. M. Hartford, T. J. Foster, G. Peters, B. E. Kehrel, and M. Herrmann Protein A is the von Willebrand factor binding protein on Staphylococcus aureus Blood, September 15, 2000; 96(6): 2149 - 2156. [Abstract] [Full Text] [PDF] E. Monnet and F. Fauvel-Lafeve A New Platelet Receptor Specific to Type III Collagen.