G Protein Signaling from Activated Rat Frizzled-1 to the β-Catenin-Lef-Tcf Pathway

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Abstract
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 β2-adrenergic receptor (β2AR) and the cytoplasmic domains from rat Frizzled-1 (Rfz1). Stimulation of mouse F9 clones expressing the chimera (β2AR-Rfz1) with the β-adrenergic agonist isoproterenol stimulated stabilization of β-catenin, activation of a β-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 Gαq and Gαo. Thus, G proteins are elements of Wnt/Frizzled-1 signaling to the β-catenin–lymphoid-enhancer factor (LEF)-T cell factor (Tcf) pathway.