ArticleThe Journal of biological chemistry2013
Neutrophil elastase and proteinase-3 trigger G protein-biased signaling through proteinase-activated receptor-1 (PAR1).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.BioMed research international · 2016Pooled it
- SERPINE1 in ARDS: an emerging regulator of inflammation-coagulation-fibrinolysis crosstalk.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Neutrophil extracellular traps promote macrophage activation through Toll-like receptor engagement and PKA and NF-kB signaling pathways.Cell communication and signaling : CCS · 2026Article
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2026Review
- Gut-primed neutrophils activate Kupffer cells to promote hepatic injury in mouse sepsis.Nature communications · 2025Article
- From theory to platelets: unraveling the history and complexities of biased signaling.Blood vessels, thrombosis & hemostasis · 2025Review
- Protease-activated receptor 1 in the pathogenesis of cystic fibrosis.BMJ open respiratory research · 2025Article
- Article
- Review
- Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation.Research and practice in thrombosis and haemostasis · 2023Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- Neutrophil Extracellular Traps in Cerebral Ischemia/Reperfusion Injury: Friend and Foe.Current neuropharmacology · 2023Review
- Elafin and its precursor trappin-2: What is their therapeutic potential for intestinal diseases?British journal of pharmacology · 2023Review
- The innate immune response, microenvironment proteinases, and the COVID-19 pandemic: pathophysiologic mechanisms and emerging therapeutic targets.Kidney international supplements · 2022Review
- Unravelling the Role of Neutrophil Extracellular Traps in Acute Liver Failure.Cellular and molecular gastroenterology and hepatology · 2022Article
- Granzyme K initiates IL-6 and IL-8 release from epithelial cells by activating protease-activated receptor 2.PloS one · 2022Article
- Flavonoids as inhibitors of human neutrophil elastase.Journal of enzyme inhibition and medicinal chemistry · 2021Review
- A KLK4 proteinase substrate capture approach to antagonize PAR1.Scientific reports · 2021Article
- The RGS-RhoGEFs control the amplitude of YAP1 activation by serum.Scientific reports · 2021Article
- Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD.The Journal of clinical investigation · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophil proteinases released at sites of inflammation can affect tissue function by either activating or disarming signal transduction mediated by proteinase-activated receptors (PARs). Because PAR1 is expressed at sites where abundant neutrophil infiltration occurs, we hypothesized that neutrophil-derived enzymes might also regulate PAR1 signaling. We report here that both neutrophil elastase and proteinase-3 cleave the human PAR1 N terminus at sites distinct from the thrombin cleavage site. This cleavage results in a disarming of thrombin-activated calcium signaling through PAR1. However, the distinct non-canonical tethered ligands unmasked by neutrophil elastase and proteinase-3, as well as synthetic peptides with sequences derived from these novel exposed tethered ligands, selectively stimulated PAR1-mediated mitogen-activated protein kinase activation. This signaling was blocked by pertussis toxin, implicating a Gαi-triggered signal pathway. We conclude that neutrophil proteinases trigger biased PAR1 signaling and we describe a novel set of tethered ligands that are distinct from the classical tethered ligand revealed by thrombin. We further demonstrate the function of this biased signaling in regulating endothelial cell barrier integrity.
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What OpenQuestion holds
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.