Effector cell protease receptor-1 is a vascular receptor for coagulation factor Xa.
The binding and assembly of the coagulation proteases on the endothelial cell surface are important steps not only in the generation of thrombin and thrombogenesis, but also in vascular cell signaling. Effector cell protease receptor (EPR-1) was identified as a novel leukocyte cell surface receptor recognizing the coagulation serine protease Factor Xa but not the precursor Factor X. We now demonstrate that EPR-1 is expressed on vascular endothelial cells and smooth muscle cells. Northern blots of endothelial and smooth muscle cells demonstrated three abundant mRNA bands of 3.0, 1.8, and 1.3 kDa. 125I-Labeled Factor Xa bound to endothelial cells in a dose-dependent saturable manner, and the binding was inhibited by antibody to EPR-1. No specific binding was observed with a recombinant mutant Factor X in which the activation site was substituted by Arg196 --> Gln to prevent the proteolytic conversion to Xa. EPR-1 was identified immunohistochemically on microvascular endothelial and smooth muscle cells. Functionally, exposure of smooth muscle cells or endothelial cells to Factor Xa induced a 3-fold and a 2-fold increase in [3H]thymidine uptake, respectively. However, receptor occupancy alone is insufficient for mitogenic signaling because the active site of the enzyme is required for mitogenesis. Thus, EPR-1 represents a site of specific protease-receptor complex assembly, which during local initiation of the coagulation cascade could mediate cellular signaling and responses of the vessel wall.
Nicholson
A C
AC
Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
Nachman
R L
RL
Altieri
D C
DC
Summers
B D
BD
Ruf
W
W
Edgington
T S
TS
Hajjar
D P
DP
D060829:Arthropod Proteins; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D005434:Flow Cytometry; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008938:Mitosis / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D000077022:Survivin
D060829:Arthropod Proteins; C107489:BIRC5 protein, human; D065427:Factor Xa Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015842:Serine Proteinase Inhibitors; D000077022:Survivin; C063967:tick anticoagulant peptide; D012697:Serine Endopeptidases; D015951:Factor Xa