Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
Copyright policy )Activation of Endothelial Cell Protease Activated Receptor 1 by the Protein C Pathway
The coagulant and inflammatory exacerbation in sepsis is counterbalanced by the protective protein C (PC) pathway. Activated PC (APC) was shown to use the endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease activated receptor 1 (PAR1) on endothelial cells. Gene profiling demonstrated that PAR1 signaling could account for all APC-induced protective genes, including the immunomodulatory monocyte chemoattractant protein-1 (MCP-1), which was selectively induced by activation of PAR1, but not PAR2. Thus, the prototypical thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a role for this receptor cascade in protection from sepsis.
- La Jolla Institute For Allergy & Immunology United States
- La Jolla Institute For Molecular Medicine United States
- Scripps Research Institute United States
Gene Expression Profiling, Receptors, Cell Surface, Blood Coagulation Factors, Cell Line, DNA-Binding Proteins, Enzyme Activation, Mice, Gene Expression Regulation, Nuclear Receptor Subfamily 4, Group A, Member 1, Animals, Humans, Receptor, PAR-2, Receptor, PAR-1, Endothelium, Vascular, Mitogen-Activated Protein Kinases, Phosphorylation, Cells, Cultured, Chemokine CCL2, Oligonucleotide Array Sequence Analysis, Protein C
Gene Expression Profiling, Receptors, Cell Surface, Blood Coagulation Factors, Cell Line, DNA-Binding Proteins, Enzyme Activation, Mice, Gene Expression Regulation, Nuclear Receptor Subfamily 4, Group A, Member 1, Animals, Humans, Receptor, PAR-2, Receptor, PAR-1, Endothelium, Vascular, Mitogen-Activated Protein Kinases, Phosphorylation, Cells, Cultured, Chemokine CCL2, Oligonucleotide Array Sequence Analysis, Protein C
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