Different substitutions of receptor discriminator residues produce unique patterns of changes in arrestin-3 preference for particular GPCRs. To reveal the effects of the indicated mutations, agonist-induced increase in arrestin binding to M2R, β2AR, D1R, and D2R (net BRETMAX in Figs. 2 and 4) and the binding to P-Rh* (Fig. 6) were expressed in relation to those of the base mutant A87V, for which this parameter was set at 1.0 for all receptors. The results for each mutant were analyzed using two-way ANOVA with receptor and arrestin mutation as the main factors, followed by the Holm-Sidak multiple comparison test. The lines above indicate the pairs of values compared, and the stars above the lines indicate statistical significance of the difference, which is indicated as follows. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001. Error bars, S.E.