ArticleThe Journal of biological chemistry2011
The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 183 citations in OpenAlex.
- Ligand-tuned extracellular domain dynamics are correlated with signaling states in 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
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- The far extracellular CUB domain of the adhesion GPCR ADGRG6/GPR126 is a key regulator of receptor signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoding ADGRE5: How Proteolytic Cleavage and Mechanical Forces Unleash Cellular Signals.Cells · 2025Article
- GPR56/ADGRG1 induces biased Rho-ROCK-MLC and JAK-STAT3 signaling to promote amoeboid-like morphology and IL-6 upregulation in melanoma cells.Cell communication and signaling : CCS · 2025Article
- Complex G-protein signaling of the adhesion GPCR, ADGRA3.The Journal of biological chemistry · 2025Article
- N-terminal fragment shedding contributes to signaling of the full-length adhesion receptor ADGRL3.The Journal of biological chemistry · 2025Article
- Generic residue numbering of the GAIN domain of adhesion GPCRs.Nature communications · 2025Article
- Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.Nature communications · 2024Article
- Article
- Mesenchymal Transglutaminase 2 Activates Epithelial ADAM17: Link to G-Protein-Coupled Receptor 56 (ADGRG1) Signalling.International journal of molecular sciences · 2024Article
- Hexahydroquinoline Derivatives Are Selective Agonists for the Adhesion G Protein-Coupled Receptor ADGRG1/GPR56.Molecular pharmacology · 2023Article
- Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Adhesion G protein-coupled receptors: structure, signaling, physiology, and pathophysiology.Physiological reviews · 2022Review
- ELTD1 is present in extracellular vesicles derived from endothelial cells as a cleaved extracellular domain which induces in vivo angiogenesis.Journal of extracellular biology · 2022Article
- Affinity Proteomics Identifies Interaction Partners and Defines Novel Insights into the Function of the Adhesion GPCR VLGR1/ADGRV1.Molecules (Basel, Switzerland) · 2022Article
- Mechanism of tethered agonist-mediated signaling by polycystin-1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
GPR56 is an adhesion G protein-coupled receptor that plays a key role in cortical development. Mutations to GPR56 in humans cause malformations of the cerebral cortex, but little is known about the normal function of the receptor. We found that the large N terminus (NT) of GPR56 is cleaved from the rest of the receptor during processing but remains non-covalently associated with the seven-transmembrane region of the receptor, as indicated by coimmunoprecipitation of the two GPR56 fragments from both transfected cells and native tissue. We also found that truncation of the GPR56 NT results in constitutive activation of receptor signaling, as revealed by increased GPR56-stimulated signaling upon transfection of HEK-293 cells with truncated GPR56, greatly enhanced binding of β-arrestins by truncated GPR56 relative to the full-length receptor, extensive ubiquitination of truncated GPR56, and cytotoxicity induced by truncated GPR56 that could be rescued by cotransfection of cells with β-arrestin 2. Furthermore, we found that the GPR56 NT is capable of homophilic trans-trans interactions that enhance receptor signaling activity. On the basis of these findings, we suggest a model of receptor activation in which the large N terminus of GPR56 constrains receptor activity but N-terminal interactions (GPR56 NT with an extracellular ligand and/or GPR56 NT homophilic trans-trans associations) can remove this inhibitory influence of the N terminus to activate receptor signaling.
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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.