Supplementary Fig. 6: Fz-subtype specific DRPB antagonists inhibit β-catenin in Fz-specific manner.
From: Receptor subtype discrimination using extensive shape complementary designed interfaces
a, In BeWo cell line, predominantly expressing Fz5, DRPB_Fz8and DRPB_Fz7/8 inhibits β-catenin signaling with IC50 of 0.1 nM and 3.7 nM. The y-axis is normalized Luciferase reporter signaling. In all panels of this figure, cells were stimulated with 20% Wnt3a conditioned media (ATCC) in combination with 25 nM R-spondin 2 and treated with gradient concentration of DRPB proteins. b, In A375BAR cell line predominantly expressing Fz2, DRPB_Fz7/8and DRPB_Fz7inhibits β-catenin signaling with IC50 of 0.3 nM and 1.8 nM. c, In HEK293STF cell line with transfected Fz4 receptor, saturating concentration of DRPB_Fz7/8 was added to inhibit Fz7 and Fz8 subtype Fz receptor-mediated Wnt signaling (shown in Supplementary Fig. 6a and 6b). The β-catenin response therefore is predominantly mediated with Fz4 receptor. Indeed, only DRPB_Fz4 showed inhibition with IC50 of 7.5 nM. Error bar represents S.E. of three replicates. The experiments in this figure were repeated once with similar results.
