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Science 292 (5522): 1718-1722

Copyright © 2001 by the American Association for the Advancement of Science

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

Tong Liu,1 Anthony J. DeCostanzo,1 Xunxian Liu,1 Hsien-yu Wang,2 Sarah Hallagan,3 Randall T. Moon,3 Craig C. Malbon1*

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 2AR) and the cytoplasmic domains from rat Frizzled-1 (Rfz1). Stimulation of mouse F9 clones expressing the chimera (beta 2AR-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 Galpha q and Galpha o. Thus, G proteins are elements of Wnt/Frizzled-1 signaling to the beta -catenin-lymphoid-enhancer factor (LEF)-T cell factor (Tcf) pathway.

1 Department of Molecular Pharmacology and
2 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.
3 Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA.
*   To whom correspondence should be addressed. E-mail: craig{at}pharm.som.sunysb.edu

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