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Science 298 (5600): 2006-2010

Copyright © 2002 by the American Association for the Advancement of Science

Signaling of Rat Frizzled-2 Through Phosphodiesterase and Cyclic GMP

Adriana Ahumada,1 Diane C. Slusarski,2 Xunxian Liu,1 Randall T. Moon,3 Craig C. Malbon,1 Hsien-yu Wang4*

The Frizzled-2 receptor (Rfz2) from rat binds Wnt proteins and can signal by activating calcium release from intracellular stores. We show that wild-type Rfz2 and a chimeric receptor consisting of the extracellular and transmembrane portions of the beta 2-adrenergic receptor with cytoplasmic domains of Rfz2 also signaled through modulation of cyclic guanosine 3',5'-monophosphate (cGMP). Activation of either receptor led to a decline in the intracellular concentration of cGMP, a process that was inhibited in cells treated with pertussis toxin, reduced by suppression of the expression of the heterotrimeric GTP-binding protein (G protein) transducin, and suppressed through inhibition of cGMP-specific phosphodiesterase (PDE) activity. Moreover, PDE inhibitors blocked Rfz2-induced calcium transients in zebrafish embryos. Thus, Frizzled-2 appears to couple to PDEs and calcium transients through G proteins.

1 Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Center, University Medical Center, SUNY-Stony Brook, Stony Brook, NY 11794-8651, USA.
2 Department of Biological Sciences, University of Iowa, Iowa City, IA 52242, USA.
3 Howard Hughes Medical Institute, Department of Pharmacology and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA.
4 Department of Physiology and Biophysics, Diabetes and Metabolic Diseases Research Center, University Medical Center, SUNY-Stony Brook, Stony Brook, NY 11794-8661, USA.
*   To whom correspondence should be addressed. E-mail: wangh{at}pharm.sunysb.edu



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