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/

Simple collagen-related peptides (CRPs) containing a repeat Gly-Pro-Hy p sequence are highly potent platelet agonists. Like collagen, they mu st exhibit tertiary (triple-helical) and quaternary (polymeric) struct ure to activate platelets. Platelet signaling events induced by the pe ptides are the same as most of those induced by collagen. The peptides do not recognize the alpha(2) beta(1) integrin. To identify the signa ling 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 fu nctional deficiencies. These studies exclude a primary recognition rol e for CD36, von Willebrand factor (VWF), or glycoprotein (GP) IIb/IIIa . Thus, both CD36 and vWf-deficient platelets exhibited normal aggrega tion, normal fibrinogen binding, and normal expression of CD62 and CD6 3, measured by flow cytometry, in response to the peptide, and there w as normal expression of CD62 and CD63 on thrombasthenic platelets. In contrast, GPVI-deficient platelets were totally unresponsive to the pe ptide, indicating that this receptor recognizes the Gly-Pro-Hyp sequen ce in collagen. GPVI-deficient platelets showed some fibrinogen bindin g in response to collagen but failed to aggregate and to express CD62 and CD63. Collagen, but not CRP-XL, contains binding sites for alpha(2 ) beta(1). Therefore, it is possible that collagen still induces some signaling via alpha(2) beta(1), leading to activation of GPIIb/IIIa. O ur findings are consistent with a two-site, two-step model of collagen interaction with platelets involving recognition of specific sequence s in collagen by an adhesive receptor such as alpha(2) beta(1) to arre st platelets under flow and subsequent recognition of another specific collagen sequence by an activatory receptor, namely GPVI. (C) 1998 by The American Society of Hematology.