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Volume 271, Number 29, Issue of July 19, 1996 pp. 17491-17498
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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The Endothelial Cell Protein C Receptor
CELL SURFACE EXPRESSION AND DIRECT LIGAND BINDING BY THE SOLUBLE RECEPTOR

(Received for publication, February 27, 1996, and in revised form, May 10, 1996)

Kenji Fukudome , Shinichiro Kurosawa , Deborah J. Stearns-Kurosawa , Xuhua He ^§ , Alireza R. Rezaie and Charles T. Esmon ^§

From the  Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Departments of Pathology, Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, and ^§ Howard Hughes Medical Institute, Oklahoma City, Oklahoma 73104

Expression of the endothelial cell protein C receptor (EPCR) gene in mammalian cells imparts the capacity to bind activated protein C (APC) or protein C. Immunochemical analysis of CCD41, apparently the murine homologue of EPCR, suggested centrosomal localization, raising questions about the location of the EPCR gene product and its role in protein C binding. In this study, we express a soluble form of EPCR, demonstrate EPCR expression on the cell surface, and direct binding between soluble EPCR and protein C/APC. Affinity purified polyclonal and a monoclonal antibody against EPCR bound to the cell surface of EPCR-transfected cells but not to control cells. A 49-kDa protein, a mass similar to soluble EPCR, was immunoprecipitated from the cell surface of endothelium and cells transfected with human EPCR but not from control cells. The FLAG^TM antibody and APC bound to cells expressing an EPCR construct containing the FLAG^TM epitope located in a putative extracellular domain, whereas an EPCR construct truncated just before the putative transmembrane domain produced only soluble EPCR antigen. Soluble EPCR inhibited APC binding to EPCR expressing cells in a concentration-dependent fashion, K_d (app) = 29 nM and bound to immobilized protein C in a Ca²⁺-dependent fashion. Thus, EPCR is a type 1 transmembrane protein that binds directly to APC.

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