ArticleJournal of thrombosis and haemostasis : JTH2010
Coagulation factor Xa cleaves protease-activated receptor-1 and mediates signaling dependent on binding to the endothelial protein C receptor.
Article in Journal of thrombosis and haemostasis : JTH, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 69 citations in OpenAlex.
- Measuring Neural Factor X Pathway Activity in Rodent Glioma Cell Culture and Brain Slices.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Reframing ATR: from the immunologic/nonimmunologic dichotomy to adaptive, innate, and physicochemical drivers within the allergy-inflammation-coagulation axis.Frontiers in immunology · 2026Review
- Protease-activated receptors in vascular smooth muscle cells: a bridge between thrombo-inflammation and vascular remodelling.Cell communication and signaling : CCS · 2025Review
- Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy.Cancers · 2024Review
- Endothelial Protein C Receptor and Its Impact on Rheumatic Disease.Journal of clinical medicine · 2024Review
- Rivaroxaban attenuates neutrophil maturation in the bone marrow niche.Basic research in cardiology · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Markers for human haematopoietic stem cells: The disconnect between an identification marker and its function.Frontiers in physiology · 2022Review
- Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves.Biomolecules · 2021Review
- Analysis of 180 Genetic Variants in a New Interactive FX Variant Database Reveals Novel Insights into FX Deficiency.TH open : companion journal to thrombosis and haemostasis · 2021Article
- Platelet Membrane Receptor Proteolysis: Implications for Platelet Function.Frontiers in cardiovascular medicine · 2020Review
- Role of the protease-activated receptor 1 in regulating the function of glial cells within central and peripheral nervous system.Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- Coagulation Factor Xa Promotes Solid Tumor Growth, Experimental Metastasis and Endothelial Cell Activation.Cancers · 2019Article
- Article
- β-arrestin-2 in PAR-1-biased signaling has a crucial role in endothelial function via PDGF-β in stroke.Cell death & disease · 2019Article
- Review
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- The coagulation system in atherothrombosis: Implications for new therapeutic strategies.Research and practice in thrombosis and haemostasis · 2018Article
- Thrombin Inhibition Reduces the Expression of Brain Inflammation Markers upon Systemic LPS Treatment.Neural plasticity · 2018Article
- Uncoupling of the profibrotic and hemostatic effects of thrombin in lung fibrosis.JCI insight · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
objectiveCoagulation is intrinsically tied to inflammation, and both proinflammatory and anti-inflammatory responses are modulated by coagulation protease signaling through protease-activated receptor-1 (PAR1). Activated factor X (FXa) can elicit cellular signaling through PAR1, but little is known about the role of cofactors in this pathway. Endothelial protein C receptor (EPCR) supports PAR1 signaling by the protein C pathway, and in the present study we tested whether EPCR mediates surface recruitment and signaling of FXa. METHODS AND
resultsHere, we show that FXa binds to overexpressed as well as native endothelial EPCR. PAR1 cleavage by FXa as analyzed with conformation-sensitive antibodies and a tagged PAR1 reporter construct was strongly enhanced if EPCR was available. Anti-EPCR failed to affect the tissue factor-dependent activation of FX, but high concentrations of FXa decreased EPCR-dependent protein C activation. Most importantly, the FXa-mediated induction of Erk1/2 activation, expression of the transcript for connective tissue growth factor and barrier protection in endothelial cells required binding to EPCR.
conclusionsOur results demonstrate that EPCR plays an unexpected role in supporting cell surface recruitment, PAR1 activation, and signaling by FXa.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.