PUBLICATION
Signaling of rat frizzled-2 through phosphodiesterase and cyclic guanosine 3', 5'-monophosphate
- Authors
- Ahumada, A., Slusarski, D.C., Liu, X., Moon, R.T., Malbon, C.C. and Wang, H.-Y.
- ID
- ZDB-PUB-030113-1
- Date
- 2002
- Source
- Science (New York, N.Y.) 298: 2006-2010 (Journal)
- Registered Authors
- Moon, Randall T., Slusarski, Diane C.
- Keywords
- none
- MeSH Terms
-
- Phosphodiesterase Inhibitors/pharmacology
- Signal Transduction*
- Frizzled Receptors
- Receptors, G-Protein-Coupled
- Rats
- Cyclic GMP/metabolism*
- Recombinant Fusion Proteins/metabolism
- Embryo, Nonmammalian/metabolism
- Amino Acid Sequence
- Molecular Sequence Data
- Reverse Transcriptase Polymerase Chain Reaction
- Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
- Calcium/metabolism
- Animals
- Tumor Cells, Cultured
- Transfection
- Transducin/genetics
- Transducin/metabolism
- Phosphoric Diester Hydrolases/metabolism*
- Receptors, Neurotransmitter/chemistry
- Receptors, Neurotransmitter/metabolism*
- Culture Media, Conditioned
- Cricetinae
- Receptors, Adrenergic, beta-2/chemistry
- Receptors, Adrenergic, beta-2/metabolism
- Zebrafish
- Pertussis Toxin/pharmacology
- CHO Cells
- PubMed
- 12471263 Full text @ Science
Citation
Ahumada, A., Slusarski, D.C., Liu, X., Moon, R.T., Malbon, C.C. and Wang, H.-Y. (2002) Signaling of rat frizzled-2 through phosphodiesterase and cyclic guanosine 3', 5'-monophosphate. Science (New York, N.Y.). 298:2006-2010.
Abstract
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 beta2-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping