Endothelial cell protein C receptor-dependent signalingPendurthi, Usha, R.; Rao, L. Vijaya, MohanCurrent Opinion in Hematology: May 2018 - Volume 25 - Issue 3 - p 219–226 doi: 10.1097/MOH.0000000000000416 VASCULAR BIOLOGY: Edited by Edward F. Plow Abstract Author Information Purpose of review Endothelial cell protein C receptor (EPCR), a transmembrane glycoprotein present on the surface of endothelial cells and other cell types, is an essential component of the protein C (PC) anticoagulant system. EPCR is also shown to play a critical role in mediating activated protein C (APC)-induced cytoprotective signaling. The purpose of this review is to outline the mechanisms of EPCR-dependent cell signaling and discuss recent findings made in this area. Recent findings Recent studies showed that the cleavage of protease-activated receptor (PAR)1 at a noncanonical site by APC–EPCR or the canonical site by thrombin when PC occupies EPCR induces β-arrestin-2-mediated biased cytoprotective signaling. Factor VIIa binding to EPCR is also shown to induce the cytoprotective signaling. EPCR is found to be a reliable surface marker for identifying human hematopoietic stem cells in culture. EPCR, binding to diverse ligands, is thought to play a role in the pathogenesis of severe malaria, immune functions, and cancer by either blocking the APC-mediated signaling or by mechanisms that are yet to be elucidated. Summary Recent studies provide a mechanistic basis to how EPCR contributes to PAR1-mediated biased signaling. EPCR may play a role in influencing a wide array of biological functions by binding to diverse ligands. Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA Correspondence to Usha R. Pendurthi, Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA. Tel: +1 903 877 7342; e-mail: Usha.Pendurthi@uthct.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.