β-arrestins are a family of adapter proteins that bind to activated G-protein-coupled receptors (GPCRs). Binding of these adapters is known to be important for termination of G-protein activation, but recent work indicates that it also allows GPCRs to stimulate additional signalling pathways. Louis Luttrell and Robert Lefkowitz discuss the signal-terminating functions ofβ-arrestins as well as the novel signalling functions of these adapters. The proteins are able to terminate GPCR signalling through three distinct mechanisms: desensitization (steric inhibition of G protein activation);sequestration (promotion of receptor endocytosis); and downregulation (sorting of receptors for degradation). Their signalling function rests on their ability to function as scaffolds: β-arrestins can interact with a variety of signalling molecules, including Src kinases and members of the ERK and JNK MAP-kinase cascades. β-arrestin-dependent activation of Src, for example,is implicated in stimulation of neutrophil degranulation by the chemokine receptor CXCR1. Given such scaffold functions, a key role of β-arrestins...

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