期刊
CURRENT OPINION IN HEMATOLOGY
卷 25, 期 3, 页码 219-226出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0000000000000416
关键词
activated protein C; cytoprotective signaling; endothelial cell protein C receptor; factor VIIa; protease-activated receptors
类别
资金
- Mesothelioma Applied Research Foundation
- National Heart, Lung and Blood Institute [HL107483]
Purpose of reviewEndothelial 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 findingsRecent 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 -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.SummaryRecent 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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