Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans
J. Clin. Invest. Supriya Srinivasan, et al. 114:1158 doi:10.1172/JCI21927 [Go to this article.]

Figure 2
N-terminal MC4R mutation does not impair ligand action. WT and mutant MC4Rs were transiently transfected into HEK293 cells stably expressing luciferase under the control of a cAMP response element promoter. Cells were stimulated with increasing amounts of α-MSH (A and B) or with α-MSH 10^–8 M and increasing concentrations of AGRP (C and D), and luci ferase activity was measured to generate dose response curves. Data were normalized to maximal α-MSH stimulation after subtraction of basal activity and were fitted by nonlinear regression. Each point represents the mean ± SEM of at least two independent experiments. The best-fit estimate of the EC₅₀ (A and B) or the IC₅₀ (C and D) and their 95% confidence intervals are indicated for each data set. There was no statistical difference between the WT EC₅₀ and EC₅₀ for each of the mutants (A and B) nor between the WT IC₅₀ and IC₅₀ for each of the mutants (C and D; for all in A–D, P > 0.05 in an F test under the null hypothesis “log EC₅₀/IC₅₀ same for WT and mutants”). RLU, relative luminescence units.