Physiologic and cardiac roles of beta-arrestins.
Beta-arrestin1 and beta-arrestin2 were initially identified by sequence homology to visual arrestins and by their ability to bind to and inactivate signaling of the beta-2-adrenergic receptor in a process known as desensitization. While the role of beta-arrestins in desensitization has been known for some time, more recent evidence has revealed that beta-arrestins are multifunctional scaffolding proteins that are involved in numerous aspects of G protein-coupled receptor (GPCR) signaling. Interestingly, exciting new data shows that beta-arrestins can mediate signaling in their own right independent of classical second messenger mediated signaling, and that this beta-arrestin-mediated signaling may be cardioprotective. Identifying novel ligands for GPCRs that can block G protein-mediated signaling while simultaneously promoting beta-arrestin-mediated signaling could provide powerful new therapies for cardiac disease.
Patel
Priyesh A
PA
Duke University School of Medicine, Durham, North Carolina 27710, USA.
Tilley
Douglas G
DG
Rockman
Howard A
HA
D058666:Adrenergic beta-2 Receptor Agonists; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000378:metabolism*; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D011173:Portraits as Topic; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015290:Second Messenger Systems; D000071557:beta-Arrestins
D058666:Adrenergic beta-2 Receptor Agonists; D019390:Arrestins; D002316:Cardiotonic Agents; D018343:Receptors, Adrenergic, beta-2; D000071557:beta-Arrestins