ArticleeLife2022
Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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
11 citing papers in PubMed, 16 citations in OpenAlex.
- Non-canonical cleavage of GPR125/ADGRA3 releases extracellular receptor fragments detectable in cerebrospinal fluid.iScience · 2026Article
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Anti-Inflammatory Potential of Novel Tethered Agonists of the Adhesion G Protein-Coupled Receptor F5.International journal of molecular sciences · 2026Article
- GαInternational journal of molecular sciences · 2025Article
- Exploring the Cellular and Molecular Landscape of Idiopathic Pulmonary Fibrosis: Integrative Multi-Omics and Single-Cell Analysis.Biomedicines · 2025Article
- Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease.Genes & diseases · 2025Review
- Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.Nature biomedical engineering · 2024Article
- GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2024Article
- The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects.Cell death & disease · 2024Article
- The clinical relevance of the adhesion G protein-coupled receptor F5 for human diseases and cancers.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Disentangling autoproteolytic cleavage from tethered agonist-dependent activation of the adhesion receptor ADGRL3.The Journal of biological chemistry · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
The mechanistic details of the tethered agonist mode of activation for the adhesion GPCR ADGRF5/GPR116 have not been completely deciphered. We set out to investigate the physiological importance of autocatalytic cleavage upstream of the agonistic peptide sequence, an event necessary for NTF displacement and subsequent receptor activation. To examine this hypothesis, we characterized tethered agonist-mediated activation of GPR116 in vitro and in vivo. A knock-in mouse expressing a non-cleavable GPR116 mutant phenocopies the pulmonary phenotype of GPR116 knock-out mice, demonstrating that tethered agonist-mediated receptor activation is indispensable for function in vivo. Using site-directed mutagenesis and species-swapping approaches, we identified key conserved amino acids for GPR116 activation in the tethered agonist sequence and in extracellular loops 2/3 (ECL2/3). We further highlight residues in transmembrane 7 (TM7) that mediate stronger signaling in mouse versus human GPR116 and recapitulate these findings in a model supporting tethered agonist:ECL2 interactions for GPR116 activation.
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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 Socratic graph.