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

• Published in: Science (American Association for the Advancement of Science) Vol. 292; no. 5522; pp. 1718 - 1722
• Main Authors: Liu, Tong, DeCostanzo, Anthony J., Liu, Xunxian, Wang, Hsien-yu, Hallagan, Sarah, Moon, Randall T., Malbon, Craig C.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 01.06.2001; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Animals; Antibodies; b-catenin; b2-adrenergic receptors; beta Catenin; Biological and medical sciences; Biomolecules; Cadherins; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cells; Chimeras; Cloning, Molecular; COS cells; Cytoskeletal Proteins - metabolism; Embryo, Nonmammalian - metabolism; Embryos; Endoderm - physiology; Frizzled Receptors; Frizzled-a protein; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genes; Genes, Reporter; Glycoproteins; Guanosine Triphosphate - metabolism; Heterotrimeric GTP-Binding Proteins - metabolism; Inhibition; Isoproterenol - metabolism; Isoproterenol - pharmacology; L cells; LEF protein; Membranes; Mice; Molecular and cellular biology; Molecular Sequence Data; Pertussis Toxin; Pharmacology; Propranolol - metabolism; Propranolol - pharmacology; Protein subunits; Proteins; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptors; Receptors, Adrenergic, beta-2 - chemistry; Receptors, Adrenergic, beta-2 - genetics; Receptors, Adrenergic, beta-2 - metabolism; Receptors, G-Protein-Coupled; Receptors, Neurotransmitter - chemistry; Receptors, Neurotransmitter - genetics; Receptors, Neurotransmitter - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; RNA; Rodents; Signal Transduction; Tcf protein; Trans-Activators; Transcription Factors - metabolism; Transfection; Tumor Cells, Cultured; Virulence Factors, Bordetella - pharmacology; Whooping cough; Wnt protein; Wnt Proteins; Xenopus; Xenopus Proteins; Zebrafish Proteins; Signal transduction; Vertebrata; Mammalia; Rat; Rodentia; Development; Catenin; G protein; Biological receptor
• ISSN: 0036-8075; 1095-9203
• 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 β2-adrenergic receptor (β2AR) and the cytoplasmic domains from rat Frizzled-1 (Rfzl). 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.