Modulation of xlMC3R.L/S signaling by xlMRAPs. (A, B, C, D, E, and F) Dose–response curves of agonist (α-MSH) (0 M, 10−11 to 10−7 M) stimulated cAMP production of xlMC3R.L with different ratio of (A) xlMRAP2.L, (B) xlMRAP2.S, and (C) xlMRAP1.L. Ligand stimulation of xlMC3R.S was also modulated by (D) xlMRAP2.L, (E) xlMRAP2.S, and (F) xlMRAP1.L. All data of ligand stimulation were normalized to the maxima of 1:0, 1:1, 1:3, and 1:6 curves in the ligand stimulation assay. Data were plotted as the mean ± s.e.m. of three independent experiments performed in triplicate. (G, H, I, J, K, and L) The antagonistic ability of SHU9119 (10−11 to 10−6 M) in the presence of α-MSH (EC80) induced the alteration of xlMC3R.L signaling with different amounts of (G) xlMRAP2.L, (H) xlMRAP2.S, and (I) xlMRAP1.L. Antagonistic ability of SHU9119 (10−11 to 10−6 M) in the presence of α-MSH (EC80) induced the alteration of xlMC3R.S signaling was also regulated by (J) xlMRAP2.L, (K) xlMRAP2.S, and (L) xlMRAP1.L. All data of antagonistic ability were normalized to the maxima of 1:0, 1:1, 1:3, and 1:6 curves. Data were plotted as the mean ± s.e.m. of three independent experiments performed in triplicate.