Beta-arrestin multimers: does a crowd help or hinder function?
In this issue of the Biochemical Journal, Xu et al. describe how they use a spot peptide array to identify a unique sequence within beta-arrestin-2 that is required for both multimerization and ERK1/2 (extracellular-signal-related kinase 1/2) scaffolding. They provide evidence that dimers may serve as more than just 'storage forms' of beta-arrestins, incapable of interacting with receptors but, rather, perhaps, adding to the specificity of G-protein-coupled-receptor signalling. They show that key charged residues within this dimerization interface of beta-arrestin-2 block association with ERK1/2 and subsequent activation of ERK1/2 by beta(2)-adrenergic receptors, while internalization is unaffected. They suggest that self-association may serve as a means of sheltering scaffolding sites on beta-arrestins from specific binding partners to prevent constitutive activation of key signalling pathways. These studies enhance our understanding of how beta-arrestins can juggle their roles as scaffolds of multiple pathways in response to diverse signals.
Division of Biomedical Sciences and Cell, Molecular, and Developmental Biology, University of California Riverside, 1620 Computer Statistics Building, Riverside, CA 92521, USA. katie.defea@ucr.edu
Kathryn Anne
KA
DeFea
D000595:Amino Acid Sequence; D019390:Arrestins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D015398:Signal Transduction; D000071557:beta-Arrestins
D019390:Arrestins; D000071557:beta-Arrestins; D020929:Mitogen-Activated Protein Kinase Kinases