G protein signaling from activated rat Frizzled-1 to the β-catenin-Lef-Tcf pathway

The frizzled receptors, which mediate development and display seven hydrophobic, membrane-spanning segments, are cell membrane-localized. We constructed a chimeric receptor with the ligand-binding and transmembrane segments from the beta (2)-adrenergic receptor (beta (2)AR) and the cytoplasmic domains from rat Frizzled-1 (Rfz1). Stimulation of mouse F9 clones expressing the chimera (beta (2)AR-Rfz1) with the beta -adrenergic agonist isoproterenol stimulated stabilization of beta -catenin, activation. of a beta -catenin-sensitive promoter, and formation of primitive endoderm. The response was blocked by inactivation of pertussis toxin-sensitive, heterotrimeric guanine nucleotide-binding proteins (G proteins) and by depletion of G alphaq and G alphao. Thus, G proteins are elements of Wnt/Frizzled-1 signaling to the beta -catenin-lymphoid-enhancer factor (LEF)-T cell factor (Tcf) pathway.