ArticlePloS one2022
Granzyme K initiates IL-6 and IL-8 release from epithelial cells by activating protease-activated receptor 2.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- PD-1⁺ CD8⁺ T cells: roles of PD-1 beyond an exhaustion marker.Seminars in immunopathology · 2026Review
- Protease-Activated Receptor-2 Promotes Metastasis: An Emerging Therapeutic Target.Molecular cancer research : MCR · 2026Review
- A chemiluminescence assay targeting granzyme A activity for monitoring inflammatory bowel disease.Nature biomedical engineering · 2026Article
- Extracellular granzyme K enhances PD-L1 transcription and stability via F2RL1 activation to facilitate tumor immune evasion in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Gestational and lactational dietary supplementation with live yeast partially attenuates inflammatory responses to lipopolysaccharide challenge in newly weaned piglets.Journal of animal science · 2026Article
- Targeting bone marrow mesenchymal stromal cell-derived IL-6 to overcome acute myeloid leukemia chemoresistance.Blood advances · 2025Observational
- Angiogenic CD8 T cells from PWH induce Granzymes-dependent PAR1 activation promoting endothelial inflammation.bioRxiv : the preprint server for biology · 2025Article
- GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling.Inflammation · 2025Article
- Biased agonism of G protein-coupled receptors as a novel strategy for osteoarthritis therapy.Bone research · 2025Review
- Pro-inflammatory granzyme K contributes extracellularly to disease.Frontiers in immunology · 2025Review
- Immune cell single-cell RNA sequencing analyses link an age-associated T cell subset to symptomatic benign prostatic hyperplasia.Frontiers in immunology · 2025Article
- Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models.Cell reports · 2024Article
- Granzyme serine proteases in inflammation and rheumatic diseases.Nature reviews. Rheumatology · 2024Review
- Granzyme KBest practice & research. Clinical rheumatology · 2024Review
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis.Frontiers in immunology · 2024Article
- Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models.bioRxiv : the preprint server for biology · 2023Article
- CRISPR/Cas13d targeting GZMA in PARs pathway regulates the function of osteoclasts in chronic apical periodontitis.Cellular & molecular biology letters · 2023Article
- NK- and T-cell granzyme B and K expression correlates with age, CMV infection and influenza vaccine-induced antibody titres in older adults.Frontiers in aging · 2022Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Granzyme K (GzmK) is a tryptic member of the granzyme family of chymotrypsin-like serine proteases produced by cells of the immune system. Previous studies have indicated that GzmK activates protease-activated receptor 1 (PAR1) enhancing activation of monocytes and wound healing in endothelial cells. Here, we show using peptides and full length proteins that GzmK and, to a lesser extent the related protease GzmA, are capable of activating PAR1 and PAR2. These cleavage events occur at the canonical arginine P1 residue and involve exosite interactions between protease and receptor. Despite cleaving PAR2 at the same point as trypsin, GzmK does not induce a classical Ca2+ flux but instead activates a distinct signalling cascade, involving recruitment of β-arrestin and phosphorylation of ERK. In epithelial A549 cells, PAR2 activation by GzmK results in the release of inflammatory cytokines IL-6 and IL-8. These data suggest that during an immune response GzmK acts as a pro-inflammatory regulator, rather than as a cytotoxin.
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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.