Usha R Pendurthi1, L Vijaya Mohan Rao. 1. Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA.
Abstract
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.
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.
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