ArticlePloS one2014
Cathepsin S signals via PAR2 and generates a novel tethered ligand receptor agonist.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 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
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- MMP1 and PRSS23 induce PARCommunications biology · 2026Article
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- The Many Faces of Protease-Activated Receptor 2 in Kidney Injury.Biomedicines · 2025Review
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Protease activated receptor 2 as a novel druggable target for the treatment of metabolic dysfunction-associated fatty liver disease and cancer.Frontiers in immunology · 2024Review
- Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019.British journal of pharmacology · 2022Article
- Cathepsin S is a novel target for age-related dry eye.Experimental eye research · 2022Article
- Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment.Cardiovascular research · 2021Review
- Article
- Electroacupuncture intervention of visceral hypersensitivity is involved in PAR-2-activation and CGRP-release in the spinal cord.Scientific reports · 2020Article
- Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics.Respiratory research · 2020Review
- Cathepsin S and Protease-Activated Receptor-2 Drive Alloimmunity and Immune Regulation in Kidney Allograft Rejection.Frontiers in cell and developmental biology · 2020Article
- Performance evaluation of molecular docking and free energy calculations protocols using the D3R Grand Challenge 4 dataset.Journal of computer-aided molecular design · 2019Article
- Review
- Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases.Thrombosis journal · 2019Review
- Structural Characterization of Agonist Binding to Protease-Activated Receptor 2 through Mutagenesis and Computational Modeling.ACS pharmacology & translational science · 2018Article
- Role of the blood coagulation cascade in hepatic fibrosis.American journal of physiology. Gastrointestinal and liver physiology · 2018Review
- Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren's Syndrome patients.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Protease-activated receptor-2 is widely expressed in mammalian epithelial, immune and neural tissues. Cleavage of PAR2 by serine proteases leads to self-activation of the receptor by the tethered ligand SLIGRL. The contribution of other classes of proteases to PAR activation has not been studied in detail. Cathepsin S is a widely expressed cysteine protease that is upregulated in inflammatory conditions. It has been suggested that cathepsin S activates PAR2. However, cathepsin S activation of PAR2 has not been demonstrated directly nor has the potential mechanism of activation been identified. We show that cathepsin S cleaves near the N-terminus of PAR2 to expose a novel tethered ligand, KVDGTS. The hexapeptide KVDGTS generates downstream signaling events specific to PAR2 but is weaker than SLIGRL. Mutation of the cathepsin S cleavage site prevents receptor activation by the protease while KVDGTS retains activity. In conclusion, the range of actions previously ascribed to cysteine cathepsins in general, and cathepsin S in particular, should be expanded to include molecular signaling. Such signaling may link together observations that had been attributed previously to PAR2 or cathepsin S individually. These interactions may contribute to inflammation.
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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.