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Molecular Cell 24 , 643–652, December 8, 2006 ª2006 Elsevier Inc. DOI 10.1016/j.molcel.2006.11.007 New Roles for b-Arrestins in Review Cell Signaling: Not Just for Seven-Transmembrane Receptors Robert J. Lefkowitz,1,2,* Keshava Rajagopal,3 receptor endocytosis and trafficking (Lefkowitz and and Erin J. Whalen1 Shenoy, 2005). 1 Department of Medicine The arrestins constitute a small gene family of four 2 Department of Biochemistry proteins (Krupnick and Benovic, 1998). Arrestins1 and 3 Department of Surgery -4 (X arrestin) are confined, respectively, to retinal rods Howard Hughes Medical Institute and cones, while b-arrestins1 and -2 (arrestins2 and -3) Duke University Medical Center are ubiquitously distributed in mammalian tissues. Ar- Durham, North Carolina 27710 restin homologs are found in a variety of primitive animal species such as Caenorhabditis elegans and Drosophila melanogaster, but not in yeast. However, a distant b-arrestins, originally discovered as molecules that structural relative was recently identified in the fungus bind to and desensitize the activated and phosphory- Aspergillus nidulans (Herranz et al., 2005). The arrestins lated form of the G protein-coupled b2-adrenergic were originally discovered by virtue of their ability to receptor (b2-AR), have recently emerged as multifun