Publication Date:
2002-12-10
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ahumada, Adriana -- Slusarski, Diane C -- Liu, Xunxian -- Moon, Randall T -- Malbon, Craig C -- Wang, Hsien-yu -- T32-DK07521/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2002 Dec 6;298(5600):2006-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Center, University Medical Center, SUNY-Stony Brook, Stony Brook, NY 11794-8651, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12471263" target="_blank"〉PubMed〈/a〉
Keywords:
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/metabolism
;
Receptors, G-Protein-Coupled
;
Receptors, Neurotransmitter/chemistry/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Reverse Transcriptase Polymerase Chain Reaction
;
*Signal Transduction
;
Transducin/genetics/metabolism
;
Transfection
;
Tumor Cells, Cultured
;
Zebrafish
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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