ArticleCell reports2014
A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 165 papers, 1 of them a synthesis that pooled it.
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Who cites it
165 citing papers in PubMed, 1 synthesis or guideline pooled it, 289 citations in OpenAlex.
- Anthropometric Equations to Determine Maximum Height in Adults ≥ 60 Years: A Systematic Review.International journal of environmental research and public health · 2022Pooled it
- The isolated Stachel peptide of the adhesion G protein-coupled receptor ADGRG6 is predominantly disordered with local helical propensity.Biophysical journal · 2026Article
- Microbial GAIN domains undergo autoproteolysis and enable release of diverse cell-surface-associated proteins.Current biology : CB · 2026Article
- Review
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in an adhesion GPCR.Science advances · 2026Article
- Tethered agonist- and GAIN domain-independent signaling of an adhesion GPCR.Science advances · 2026Article
- 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
- Adgrg6/Gpr126 is required for compact wall integrity and establishing trabecular identity during cardiac trabeculation.Nature communications · 2026Article
- The isolatedbioRxiv : the preprint server for biology · 2026Article
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- Synaptic Cell Adhesion: A Structural Perspective.Advances in neurobiology · 2026Review
- Structure of the GNature communications · 2025Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Self-cleavage of the GAIN domain of adhesion G protein-coupled receptors requires multiple domain-extrinsic factors.Nature communications · 2025Article
- Domain-specific N-glycosylation of the adhesion G-protein-coupled receptor ADGRG6 N-terminal fragment regulates trafficking, proteolytic processing, and signaling.Molecular biology of the cell · 2025Article
- Identification and localization of adhesion G protein-coupled receptor expression in the murine kidney.American journal of physiology. Renal physiology · 2025Article
- The mechanosensitive adhesion G protein-coupled receptor 133 (GPR133/ADGRD1) enhances bone formation.Signal transduction and targeted therapy · 2025Article
- Complex G-protein signaling of the adhesion GPCR, ADGRA3.The Journal of biological chemistry · 2025Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Adhesion G protein-coupled receptors (aGPCRs) comprise the second largest yet least studied class of the GPCR superfamily. aGPCRs are involved in many developmental processes and immune and synaptic functions, but the mode of their signal transduction is unclear. Here, we show that a short peptide sequence (termed the Stachel sequence) within the ectodomain of two aGPCRs (GPR126 and GPR133) functions as a tethered agonist. Upon structural changes within the receptor ectodomain, this intramolecular agonist is exposed to the seven-transmembrane helix domain, which triggers G protein activation. Our studies show high specificity of a given Stachel sequence for its receptor. Finally, the function of Gpr126 is abrogated in zebrafish with a mutated Stachel sequence, and signaling is restored in hypomorphic gpr126 zebrafish mutants upon exogenous Stachel peptide application. These findings illuminate a mode of aGPCR activation and may prompt the development of specific ligands for this currently untargeted GPCR family.
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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.