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

DOI Web Site 3 Citations
  • Tong Liu
    Department of Molecular Pharmacology and
  • Anthony J. DeCostanzo
    Department of Molecular Pharmacology and
  • Xunxian Liu
    Department of Molecular Pharmacology and
  • Hsien-yu Wang
    Department of Physiology, Diabetes and Metabolic Diseases Research Center, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794–8651, USA.
  • Sarah Hallagan
    Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA.
  • Randall T. Moon
    Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA.
  • Craig C. Malbon
    Department of Molecular Pharmacology and

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Description

<jats:p> The <jats:italic>frizzled</jats:italic> 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 β <jats:sub>2</jats:sub> -adrenergic receptor (β <jats:sub>2</jats:sub> AR) and the cytoplasmic domains from rat Frizzled-1 (Rfz1). Stimulation of mouse F9 clones expressing the chimera (β <jats:sub>2</jats:sub> AR-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. </jats:p>

Journal

  • Science

    Science 292 (5522), 1718-1722, 2001-06

    American Association for the Advancement of Science (AAAS)

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