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
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Calcium/metabolism
  • Cricetinae
  • Culture Media, Conditioned
  • Cyclic GMP/metabolism*
  • Embryo, Nonmammalian/metabolism
  • Frizzled Receptors
  • Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
  • Molecular Sequence Data
  • Pertussis Toxin/pharmacology
  • Phosphodiesterase Inhibitors/pharmacology
  • Phosphoric Diester Hydrolases/metabolism*
  • Rats
  • Receptors, Adrenergic, beta-2/chemistry
  • Receptors, Adrenergic, beta-2/metabolism
  • Receptors, G-Protein-Coupled
  • Receptors, Neurotransmitter/chemistry
  • Receptors, Neurotransmitter/metabolism*
  • Recombinant Fusion Proteins/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Transducin/genetics
  • Transducin/metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Zebrafish
PubMed
12471263 Full text @ Science
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping