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Signaling of Rat Frizzled-2 Through Phosphodiesterase and Cyclic GMP
Adriana Ahumada,1Diane C. Slusarski,2Xunxian Liu,1Randall T. Moon,3Craig C. Malbon,1Hsien-yu Wang4*
The Frizzled-2 receptor (Rfz2) from rat binds Wnt
proteins and can signal by activating calcium release from
intracellularstores. We show that wild-type Rfz2 and a chimeric
receptor consistingof the extracellular and transmembrane portions of
the 2-adrenergicreceptor with cytoplasmic domains of
Rfz2 also signaled throughmodulation of cyclic guanosine
3',5'-monophosphate (cGMP). Activationof either receptor led to a
decline in the intracellular concentrationof cGMP, a process that was
inhibited in cells treated with pertussistoxin, reduced by suppression
of the expression of the heterotrimericGTP-binding protein (G
protein) transducin, and suppressed throughinhibition of cGMP-specific
phosphodiesterase (PDE) activity.Moreover, PDE inhibitors blocked
Rfz2-induced calcium transientsin zebrafish embryos. Thus,
Frizzled-2 appears to couple to PDEsand 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
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