Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation

This study demonstrates that the human platelet F11 receptor (F11R) functio ns as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd pr otein duplex that serves as the binding site through which a stimulatory mo noclonal antibody causes platelet aggregation and granule secretion. A phys iological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysio logical role for the F11R was revealed by demonstrating the presence of F11 R-antibodies in patients with thrombocytopenia, Adhesion of platelets throu gh the F11R resulted in events characteristic of the action of cell adhesio n molecules (CAMs), To determine the structure of this protein, we cloned t he F11R cDNA from human platelets. The predicted amino acid sequence demons trated that it is an integral membrane protein and an immunoglobulin superf amily member containing 2 extracellular C2-type domains. The structure of t he F11R as a member of a CAM family of proteins and its activity in mediati ng adhesion confirm each another. We conclude that the F11R is a platelet-m embrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion t hat are dependent on both the Fc gamma RII and the GPIIb/IIIa Integrin and that may be involved in pathophysiological processes associated with certai n thrombocytopenias. The second is an F11R-mediated platelet adhesion that Is not dependent on either the Fc gamma RII or the fibrinogen receptor and that appears to play a role in physiological processes associated with plat elet adhesion and aggregation. (Blood. 2000;95:2600-2609) (C) 2000 by The A merican Society of Hematology.