Beta-arrestins as regulators of signal termination and transduction: how do they determine what to scaffold?
Over the last decade β-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 β-arrestin signals, which are sometimes synergistic with, and sometimes independent of, heterotrimeric G-protein signals. β-arrestin signaling involves the recruitment of downstream signaling moieties to β-arrestins; in many cases specific sites of interaction between β-arrestins and the downstream target have been identified. As more information unfolds about the nature of β-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 β-arrestin to a specific GPCR can promote formation of a specific subset of available β-arrestin scaffolds, allowing for a higher level of specificity to given agonists. This review discusses recent advances in β-arrestin signaling, discussing the molecular details of a subset of known β-arrestin scaffolds and the significance of specific binding interactions on the ultimate cellular response.
DeFea
Kathryn A
KA
Biomedical Sciences Division, University of California-Riverside, CA 92521, USA. kathryn.defea@ucr.edu
D000595:Amino Acid Sequence; D019390:Arrestins / Q000378:metabolism*; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D000071557:beta-Arrestins
D019390:Arrestins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D010727:Phosphoric Diester Hydrolases