Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP.
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.
Ahumada
Adriana
A
Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Center, University Medical Center, SUNY-Stony Brook, Stony Brook, NY 11794-8651, USA.
Slusarski
Diane C
DC
Liu
Xunxian
X
Moon
Randall T
RT
Malbon
Craig C
CC
Wang
Hsien-yu
HY
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D017077:Culture Media, Conditioned; D006152:Cyclic GMP / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D051157:Frizzled Receptors; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008969:Molecular Sequence Data; D037342:Pertussis Toxin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015293:Transducin / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D015027:Zebrafish
D017077:Culture Media, Conditioned; D051157:Frizzled Receptors; D010726:Phosphodiesterase Inhibitors; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D011993:Recombinant Fusion Proteins; C078604:Fzd2 protein, rat; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D037342:Pertussis Toxin; D010727:Phosphoric Diester Hydrolases; D015293:Transducin; D006152:Cyclic GMP; D002118:Calcium