β-Arrestins and Cell Signaling

Upon their discovery, beta-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows that beta-arrestins can also function to activate signaling cascades independently of G protein activation. By serving as multiprotein scaffolds, the beta-arrestins bring elements of specific signaling pathways into close proximity. beta-Arrestin regulation has been demonstrated for an ever-increasing number of signaling molecules, including the mitogen-activated protein kinases ERK, JNK, and p38 as well as Akt, PI3 kinase, and RhoA. In addition,…