Expanding roles for beta-arrestins as scaffolds and adapters in GPCR signaling and trafficking.

beta-arrestins play previously unsuspected and important roles as adapters and scaffolds that localize signaling proteins to ligand-activated G-protein-coupled receptors. As with the paradigmatic role of the beta-arrestins in uncoupling receptors from G proteins (desensitization), these novel functions involve the interaction of beta-arrestin with phosphorylated heptahelical receptors. beta-arrestins interact with at least two main classes of signaling proteins. First, interaction with molecules such as clathrin, AP-2 and NSF directs the clathrin-mediated internalization of G-protein-coupled receptors. Second, interaction with molecules such as Src, Raf, Erk, ASK1 and JNK3 appears to regulate several pathways that result in the activation of MAP kinases. These recent discoveries indicate that the beta-arrestins play widespread roles as scaffolds and/or adapter molecules that organize a variety of complex signaling pathways emanating from heptahelical receptors. It is likely that additional roles for the beta-arrestins remain to be discovered.

Duke Scholars

Author Robert J. Lefkowitz Medicine, Cardiology