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) functions 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 protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcgammaRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcgammaRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation. (Blood. 2000;95:2600-2609)
Sobocka
M B
MB
Department of Anatomy/Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Sobocki
T
T
Banerjee
P
P
Weiss
C
C
Rushbrook
J I
JI
Norin
A J
AJ
Hartwig
J
J
Salifu
M O
MO
Markell
M S
MS
Babinska
A
A
Ehrlich
Y H
YH
Kornecki
E
E
D000595:Amino Acid Sequence; D016824:Antigens, Human Platelet / Q000235:genetics; D001483:Base Sequence; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003001:Cloning, Molecular; D005803:Genes, Immunoglobulin; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008969:Molecular Sequence Data; D010974:Platelet Aggregation / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D017421:Sequence Analysis
D016824:Antigens, Human Platelet; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D011956:Receptors, Cell Surface