Figure 4.

Signaling and binding profiles of missense variants with significantly altered Gɑ_sactivation. The eight missense variants (D63^ECDN, P86^ECDS, V96^ECDE, G125^ECDC, R225^3.30H, R308^5.40W, V368^6.59M, and R378^7.35C) displayed significantly (p < 0.05) decreased Gα_s activation. A, dose–response curves in cAMP accumulation for wildtype glucagon receptor and variants (wildtype n = 33, variants n = 3–6.). B, dose–response curves in β-arrestin-2 recruitment for wildtype glucagon receptor and variants (wildtype n = 31, variants n = 3–5). C, B_max values from homologous competition binding with [¹²⁵I]glucagon and unlabeled glucagon for wildtype and receptor variants (wildtype n = 13; variants n = 3–5). D, the corresponding K_D values of the competition binding. Data represent the mean ± SEM of n independent experiments performed in duplicate.