12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors.

      Annual review of pharmacology and toxicology

      Animals, Arrestins, metabolism, Drug Discovery, methods, Humans, Ligands, Models, Molecular, Phosphorylation, Protein Conformation, Receptors, G-Protein-Coupled, agonists, Signal Transduction

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The concept of biased agonism has recently come to the fore with the realization that seven-transmembrane receptors (7TMRs, also known as G protein-coupled receptors, or GPCRs) activate complex signaling networks and can adopt multiple active conformations upon agonist binding. As a consequence, the "efficacy" of receptors, which was classically considered linear, is now recognized as pluridimensional. Biased agonists selectively stabilize only a subset of receptor conformations induced by the natural "unbiased" ligand, thus preferentially activating certain signaling mechanisms. Such agonists thus reveal the intriguing possibility that one can direct cellular signaling with unprecedented precision and specificity and support the notion that biased agonists may identify new classes of therapeutic agents that have fewer side effects. This review focuses on one particular class of biased ligands that has the ability to alter the balance between G protein-dependent and β-arrestin-dependent signal transduction.

          Related collections

          Author and article information

          Journal
          21942629
          3628752
          10.1146/annurev.pharmtox.010909.105800

          Comments

          Comment on this article