Liu T, DeCostanzo A J, Liu X, Hallagan S, Moon R T, Malbon C C
Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Center, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794-8651, USA.
Science. 2001 Jun 1;292(5522):1718-22. doi: 10.1126/science.1060100.
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 beta2-adrenergic receptor (beta2AR) and the cytoplasmic domains from rat Frizzled-1 (Rfz1). Stimulation of mouse F9 clones expressing the chimera (beta2AR-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 Galphaq and Galphao. Thus, G proteins are elements of Wnt/Frizzled-1 signaling to the beta-catenin-lymphoid-enhancer factor (LEF)-T cell factor (Tcf) pathway.
卷曲受体介导发育过程，具有七个疏水的跨膜片段，定位于细胞膜。我们构建了一种嵌合受体，其配体结合和跨膜片段来自β2 - 肾上腺素能受体（β2AR），细胞质结构域来自大鼠卷曲蛋白 - 1（Rfz1）。用β - 肾上腺素能激动剂异丙肾上腺素刺激表达该嵌合体（β2AR - Rfz1）的小鼠F9克隆，可刺激β - 连环蛋白的稳定、β - 连环蛋白敏感启动子的激活以及原始内胚层的形成。百日咳毒素敏感的异源三聚体鸟嘌呤核苷酸结合蛋白（G蛋白）失活以及Gαq和Gαo的耗竭可阻断该反应。因此，G蛋白是Wnt / Frizzled - 信号传导至β - 连环蛋白 - 淋巴细胞增强因子（LEF） - T细胞因子（Tcf）途径的元件。
