ArticleBlood2014
Noncanonical PAR3 activation by factor Xa identifies a novel pathway for Tie2 activation and stabilization of vascular integrity.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Human tissue kallikrein 14 induces the expression of IL-6, IL-8, and CXCL1 in skin fibroblasts through protease-activated receptor 1 signaling.The FEBS journal · 2025Article
- Endothelial Protein C Receptor: A Multifunctional Mediator in the Pathophysiology of Rheumatoid Arthritis.Cells · 2025Review
- Recent Advances in Pathogenesis and Anticoagulation Treatment of Sepsis-Induced Coagulopathy.Journal of inflammation research · 2025Review
- An orthosteric/allosteric bivalent peptide agonist comprising covalently linked protease-activated receptor-derived peptides mimics in vitro and in vivo activities of activated protein C.Journal of thrombosis and haemostasis : JTH · 2024Article
- 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
- Selective modulation of activated protein C activities by a nonactive site-targeting nanobody library.Blood advances · 2023Article
- Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.The Journal of experimental medicine · 2022Article
- Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment.Cardiovascular research · 2021Review
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- Stroke Treatment With PAR-1 Agents to Decrease Hemorrhagic Transformation.Frontiers in neurology · 2021Review
- Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities.Journal of hematology & oncology · 2020Article
- C-terminal residues of activated protein C light chain contribute to its anticoagulant and cytoprotective activities.Journal of thrombosis and haemostasis : JTH · 2020Article
- Activated protein C in neuroprotection and malaria.Current opinion in hematology · 2019Review
- Targeting Coagulation Factor Xa Promotes Regression of Advanced Atherosclerosis in Apolipoprotein-E Deficient Mice.Scientific reports · 2019Article
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Review
- PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke.Blood · 2018Article
- Relationship between G proteins coupled receptors and tight junctions.Tissue barriers · 2018Review
- Activated protein C inhibits neutrophil extracellular trap formationThe Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial barrier protective effects of activated protein C (APC) require the endothelial protein C receptor (EPCR), protease-activated receptor (PAR) 1, and PAR3. In contrast, PAR1 and PAR3 activation by thrombin results in barrier disruption. Noncanonical PAR1 and PAR3 activation by APC vs canonical activation by thrombin provides an explanation for the functional selectivity of these proteases. Here we found that factor Xa (FXa) activated PAR1 at canonical Arg41 similar to thrombin but cleaved PAR3 at noncanonical Arg41 similar to APC. This unique PAR1-PAR3 activation profile permitted the identification of noncanonical PAR3 activation as a novel activation pathway for barrier protective tunica intima endothelial receptor tyrosine kinase 2 (Tie2). APC, FXa, and the noncanonical PAR3 tethered-ligand peptide induced prolonged activation of Tie2, whereas thrombin and the canonical PAR3 tethered-ligand peptide did not. Tie2 activation by FXa required PAR3 and EPCR. FXa and the noncanonical PAR3 tethered-ligand peptide induced Tie2- and PAR3-dependent upregulation of tight-junction-associated protein zona occludens 1 (ZO-1), translocation of ZO-1 to cell-cell borders, and the formation of typical ZO-1 honeycomb patterns that are indicative of tight-junction stabilization. These data provide intriguing novel insights into the diversification of functional selectivity of protease signaling achievable by canonical and noncanonical PAR activation, such as the activation of vascular-protective Tie2 by noncanonical PAR3 activation.
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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.