Two ubiquitously expressed forms of arrestin, arrestin-2 (ARRB1) and arrestin-3 (ARRB2), can bind and desensitize B2AR (Lohse et al. 1990, Attramadal et al. 1992, Sterne-Marr et al. 1993). Unlike visual arrestin, which has 10-fold greater affinity for phosphorylated rather than unphosphorylated rhodopsin, ARRB1 and ARRB2 show only a 2-fold difference in binding levels and are much less selective in their receptor preferences (Gurevich & Gurevich 2006). GRK-mediated receptor phosphorylation followed by arrestin binding and internalization is the classical model for GPCR desensitization. Many GPCRs have been demonstrated to require phosphorylation before they can bind arrestin, but other receptors do not appear to require phosphorylation in order to bind arrestin (see refs. included in Gurevich & Gurevich 2006). In these receptors, spatially close acidic amino acids are thought to provide sites that can bind the arrestin phosphate sensing region.