Figure 7.
ADGRG1-mediated signaling to NFAT luciferase involves activation of calcium channels but not receptor coupling to Gαq/11. A, treatment with the phospholipase Cβ inhibitor U73122 (50 μm; 8 h) had no effect on ΔNT-mediated activation of NFAT luciferase. B, treatment with the calcium channel inhibitor SKF96365 (SKF) (10 μm; 8 h) ablated activation of NFAT luciferase by both G1-ΔNT and ΔNT-L640R. Results shown are from at least four independent experiments (**, p < 0.01; ***, p < 0.001; ****, p < 0.0001 for the indicated comparisons; error bars represent S.E.). C, schematic model depicting the putative signaling pathways by which G1 stimulates SRF or NFAT luciferase activity. The N-terminal fragment is shown interacting with the extracellular stalk and potentially the extracellular loops of the transmembrane C-terminal fragment to modulate receptor signaling activity. NS, not significant; luc, luciferase; veh, vehicle; GEF, guanine nucleotide exchange factor.