Teaching old receptors new tricks: biasing seven-transmembrane receptors

By S. Rajagopal, K. Rajagopal, R. J. Lefkowitz. Nature reviews. Drug discovery, 2010

842 citations recorded by the source corpus.

Seven-transmembrane receptors (7TMRs; also known as G protein-coupled receptors) are the largest class of receptors in the human genome and are common targets for therapeutics. Originally identified as mediators of 7TMR desensitization, β-arrestins (arrestin 2 and arrestin 3) are now recognized as true adaptor proteins that transduce signals to multiple effector pathways. Signalling that is mediated by β-arrestins has distinct biochemical and functional consequences from those mediated by G proteins, and several biased ligands and receptors have been identified that preferentially signal through either G protein- or β-arrestin-mediated pathways. These ligands are not only useful tools for investigating the biochemistry of 7TMR signalling, they also have the potential to be developed into new classes of therapeutics.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e94c380263cf67065c4e5f8e6d73e338bfad76b9

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Citations in the corpus

Structure-based drug screening for G-protein-coupled receptors. (2012, background): “Carvedilol is an inverse agonsit for β2AR activation of Gs, but a partial agonist for activation of arrestin [7].”
β-arrestin-mediated receptor trafficking and signal transduction (2011, background): “biased agonism, in which receptor-activated signal transduction (and perhaps physiological effects) are channeled through only one form of active coupling (either G protein or βarrestin) [104,105].”
Multiple ligand-specific conformations of the β2-adrenergic receptor. (2011, background): “) and that multiple receptor conformations signal with different intrinsic efficacies to various signaling pathway”
Molecular Mechanism of β-Arrestin-Biased Agonism at Seven-Transmembrane Receptors (2011, background): “Several theoretical representations have been proposed to illustrate the pluridimensional nature of efficacy (25, 35).”