Beta-arrestins as regulators of signal termination and transduction: How do they determine what to scaffold?

Over the last decade beta-arrestins have emerged as pleiotropic scaffold proteins, capable of mediating numerous diverse responses to multiple agonists. Most well characterized are the G-protein-coupled receptor (GPCR) stimulated beta-arrestin signals, which are sometimes synergistic with, and sometimes independent of, heterotrimeric G-protein signals. beta-arrestin signaling involves the recruitment of downstream signaling moieties to beta-arrestins; in many cases specific sites of interaction between beta-arrestins and the downstream target have been identified. As more information unfolds about the nature of beta-arrestin scaffolding interactions, it is evident that these proteins are capable of adopting multiple conformations which in turn reveal a specific set of interacting domains. Recruitment of beta-arrestin to a specific GPCR can promote formation of a specific subset of available beta-arrestin scaffolds, allowing for a higher level of specificity to given agonists. This review discusses recent advances in beta-arrestin signaling, discussing the molecular details of a subset of known beta-arrestin scaffolds and the significance of specific binding interactions on the ultimate cellular response. (C) 2010 Elsevier Inc. All rights reserved.