title: Β-arrestin: a signaling molecule and potential therapeutic target for heart failure.
abstract: Currently, some of the most effective treatments for heart failure target GPCRs such as the beta-adrenergic receptors (β1AR and β2AR) and angiotensin II type IA receptors (AT1aR). Ligands for these receptors not only function by blocking the deleterious G-protein mediated pathway leading to heart failure, but also signal via G-protein independent pathways that involve receptor phosphorylation by G-protein receptor kinases (GRKs) leading to recruitment of the multifunctional protein, β-arrestin. Originally thought to play a role in GPCR desensitization and internalization, β-arrestin has recently been shown to mediate signaling independent of classical second messengers in a way that is often protective to the heart. The multi-functionality of β-arrestin makes it an intriguing molecule in the development of the next generation of drugs for cardiac diseases with the potential to simultaneously inhibit deleterious G-protein dependent pathways while activating beneficial β-arrestin mediated signaling. In this review, we explore various facets of β-arrestin signaling and offer a perspective on its potential role as a key signaling molecule in the treatment of heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."
authors.affiliation: Duke University School of Medicine, Durham, NC, USA.
authors.forename: Nabila
authors.initials: N
authors.lastname: Noor
authors.forename: Chetan B
authors.initials: CB
authors.lastname: Patel
authors.forename: Howard A
authors.initials: HA
authors.lastname: Rockman
mesh_terms: D000818:Animals; D019390:Arrestins / Q000737:chemistry / Q000378:metabolism*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism; D011487:Protein Conformation; D021381:Protein Transport; D059748:Proteolysis; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D018342:Receptors, Adrenergic, beta-1; D011945:Receptors, Angiotensin; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins