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Effector cell protease receptor-1 is a vascular receptor for coagulation factor Xa
A C Nicholson1, R L Nachman, D C Altieri
1Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
The Journal of Biological Chemistry
|November 8, 1996
Summary
Effector cell protease receptor-1 (EPR-1) binds coagulation Factor Xa on vascular cells, mediating cell signaling and vessel wall responses. This interaction is crucial for thrombin generation and thrombogenesis.
Area of Science:
- Vascular Biology
- Coagulation Cascade
- Cell Signaling
Background:
- Coagulation proteases on endothelial cells are key in thrombin generation and vascular signaling.
- Effector cell protease receptor-1 (EPR-1) is a leukocyte receptor for Factor Xa.
Purpose of the Study:
- To investigate EPR-1 expression and function on vascular cells.
- To determine EPR-1's role in Factor Xa binding and mitogenic signaling.
Main Methods:
- Northern blotting to detect EPR-1 mRNA in endothelial and smooth muscle cells.
- Binding assays using 125I-labeled Factor Xa and antibody inhibition.
- Immunohistochemistry to localize EPR-1 on vascular cells.
- Measurement of [3H]thymidine uptake to assess mitogenesis.
Main Results:
- EPR-1 is expressed on vascular endothelial and smooth muscle cells with distinct mRNA bands.
- Factor Xa binds to endothelial cells via EPR-1 in a saturable manner.
- Factor Xa binding to EPR-1 on smooth muscle and endothelial cells induces significant mitogenesis.
Conclusions:
- EPR-1 is a novel receptor on vascular cells mediating Factor Xa binding and cellular responses.
- EPR-1 facilitates protease-receptor complex assembly, influencing vessel wall signaling during coagulation.
- The active site of Factor Xa is essential for EPR-1-mediated mitogenic signaling.