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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
11794-8661, USA.
*
To whom correspondence should be addressed. E-mail:
wangh{at}pharm.sunysb.edu
Smoothened Signal Transduction Is Promoted by G Protein-Coupled Receptor Kinase 2.
A. R. Meloni, G. B. Fralish, P. Kelly, A. Salahpour, J. K. Chen, R. J. Wechsler-Reya, R. J. Lefkowitz, and M. G. Caron (2006)
Mol. Cell. Biol.
26, 7550-7560
|Abstract »|Full Text »|PDF »
Suppression of Cyclic GMP-dependent Protein Kinase Is Essential to the Wnt/cGMP/Ca2+ Pathway.
Expression and Localization of Secreted Frizzled-Related Protein-4 in the Rodent Ovary: Evidence for Selective Up-Regulation in Luteinized Granulosa Cells.
M. Hsieh, S. M. Mulders, R. R. Friis, A. Dharmarajan, and J. S. Richards (2003)
Endocrinology
144, 4597-4606
|Abstract »|Full Text »|PDF »
Wnt-5/pipetail functions in vertebrate axis formation as a negative regulator of Wnt/{beta}-catenin activity.
T. A. Westfall, R. Brimeyer, J. Twedt, J. Gladon, A. Olberding, M. Furutani-Seiki, and D. C. Slusarski (2003)
J. Cell Biol.
162, 889-898
|Abstract »|Full Text »|PDF »
Wnt Signaling, Ca2+, and Cyclic GMP: Visualizing Frizzled Functions.
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.
