ArticleNature communications2022
GPR97 triggers inflammatory processes in human neutrophils via a macromolecular complex upstream of PAR2 activation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
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- The therapeutic potential of orphan adhesion G-protein-coupled receptors.Nature reviews. Drug discovery · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Structural basis of GAIN domain autoproteolysis and cleavage-resistance in the adhesion G-protein coupled receptors.Nature communications · 2026Article
- Structures of proteinase 3 and the CD177 receptor complex reveal a major autoantibody epitope.EMBO reports · 2026Article
- The Role of PAR2 in MASLD Progression and HCC Development.International journal of molecular sciences · 2025Review
- An Alternative Mode of GPCR Transactivation: Activation of GPCRs by Adhesion GPCRs.International journal of molecular sciences · 2025Review
- Generic residue numbering of the GAIN domain of adhesion GPCRs.Nature communications · 2025Article
- Article
- Versatile roles for neutrophil proteinase 3 in hematopoiesis and inflammation.Immunologic research · 2024Review
- Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.Nature communications · 2024Article
- Mechanical force induced activation of adhesion G protein-coupled receptor.Mechanobiology in medicine · 2024Review
- Heterogeneity of tethered agonist signaling in adhesion G protein-coupled receptors.Cell chemical biology · 2024Article
- Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury.Redox biology · 2024Article
- Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation.Cell death and differentiation · 2024Article
- The cancer-immune dialogue in the context of stress.Nature reviews. Immunology · 2024Review
- Article
- Role of Adhesion G Protein-Coupled Receptors in Immune Dysfunction and Disorder.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
Abstract
Neutrophils play essential anti-microbial and inflammatory roles in host defense, however, their activities require tight regulation as dysfunction often leads to detrimental inflammatory and autoimmune diseases. Here we show that the adhesion molecule GPR97 allosterically activates CD177-associated membrane proteinase 3 (mPR3), and in conjugation with several protein interaction partners leads to neutrophil activation in humans. Crystallographic and deletion analysis of the GPR97 extracellular region identified two independent mPR3-binding domains. Mechanistically, the efficient binding and activation of mPR3 by GPR97 requires the macromolecular CD177/GPR97/PAR2/CD16b complex and induces the activation of PAR2, a G protein-coupled receptor known for its function in inflammation. Triggering PAR2 by the upstream complex leads to strong inflammatory activation, prompting anti-microbial activities and endothelial dysfunction. The role of the complex in pathologic inflammation is underscored by the finding that both GPR97 and mPR3 are upregulated on the surface of disease-associated neutrophils. In summary, we identify a PAR2 activation mechanism that directs neutrophil activation, and thus inflammation. The PR3/CD177/GPR97/PAR2/CD16b protein complex, therefore, represents a potential therapeutic target for neutrophil-mediated inflammatory diseases.
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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.