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The G protein-coupled receptor (GPCR) family comprises the largest class of cell surface receptors found in metazoan proteomes. Within the novel GPCR subfamily of adhesion-GPCRs, approximately 150 distinct orthologues, from invertebrates to mammals, have been identified to date. All members of this family contain a large extracellular region, often containing common protein modules, coupled to a seven-transmembrane domain via a stalk region that seems to be crucial for functionality. Owing to their unique structure, restricted expression profile and involvement in several human diseases, adhesion-GPCRs have long been proposed to have vital dual roles in cellular adhesion and signalling. More recent studies have provided structural, evolutionary, developmental and immunological insights in relation to the adhesion-GPCR family.
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http://dx.doi.org/10.1016/j.tibs.2008.07.005 | DOI Listing |
Trends Pharmacol Sci
March 2025
Institute of Cell Biology, Department of Biology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Electronic address:
Adhesion G-protein-coupled receptors (aGPCRs) play key roles in health and disease. They are unique in that they not only activate G-protein pathways but also have distinct functions that rely solely on their N termini, making them complex drug targets. To date there have been only descriptive observations about these enigmatic N terminus-only functions.
View Article and Find Full Text PDFBr J Pharmacol
March 2024
Department of Biophysics, Acibadem MAA University, School of Medicine, Istanbul, Turkey.
G protein-coupled receptors (GPCRs) constitute the largest and most diverse superfamily of mammalian transmembrane proteins. These receptors are involved in a wide range of physiological functions and are targets for more than a third of available drugs in the market. Autophagy is a cellular process involved in degrading damaged proteins and organelles and in recycling cellular components.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
February 2020
Division of General & Oncologic Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 20201, United States.
Aberrant expression, function, and mutation of G protein-coupled receptors (GPCRs) and their signaling partners, G proteins, have been well documented in many forms of cancer. These cell surface receptors and their endogenous ligands are implicated in all aspects of cancer including proliferation, angiogenesis, invasion, and metastasis. Adhesion GPCRs (aGPCRs) form the second largest family of GPCRs, most of which are orphan receptors with unknown physiological functions.
View Article and Find Full Text PDFSci Rep
January 2020
Medicinal Science and Technology, GlaxoSmithKline, Stevenage, UK.
The experimental evidence that Adhesion G Protein-Coupled Receptors (aGPCRs) functionally couple to heterotrimeric G proteins has been emerging in incremental steps, but attributing biological significance to their G protein signalling function still presents a major challenge. Here, utilising activated truncated forms of the receptors, we show that ADGRE2/EMR2 and ADGRE5/CD97 are G protein-coupled in a variety of recombinant systems. In a yeast-based assay, where heterologous GPCRs are coupled to chimeric G proteins, EMR2 showed broad G protein-coupling, whereas CD97 coupled more specifically to G, G, G and G chimeras.
View Article and Find Full Text PDFPharmacol Rev
October 2019
Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida
G protein-coupled receptors (GPCRs) remain one of the most successful targets of U.S. Food and Drug Administration-approved drugs.
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