Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP

Adriana Ahumada; Diane C Slusarski; Xunxian Liu; Randall T Moon; Craig C Malbon; Hsien-yu Wang

doi:10.1126/science.1073776

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Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP

Journal article

Peer reviewed

Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP

Adriana Ahumada, Diane C Slusarski, Xunxian Liu, Randall T Moon, Craig C Malbon and Hsien-yu Wang

Science (American Association for the Advancement of Science), Vol.298(5600), pp.2006-2010

12/06/2002

DOI: 10.1126/science.1073776

PMID: 12471263

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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.

Transfection

Signal Transduction

Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology

Calcium - metabolism

Embryo, Nonmammalian - metabolism

Molecular Sequence Data

Receptors, Neurotransmitter - chemistry

Recombinant Fusion Proteins - metabolism

Receptors, Adrenergic, beta-2 - chemistry

Transducin - metabolism

Tumor Cells, Cultured

CHO Cells

Pertussis Toxin - pharmacology

Frizzled Receptors

Amino Acid Sequence

Transducin - genetics

Cricetinae

Phosphoric Diester Hydrolases - metabolism

Receptors, G-Protein-Coupled

Phosphodiesterase Inhibitors - pharmacology

Rats

Zebrafish

Reverse Transcriptase Polymerase Chain Reaction

Receptors, Adrenergic, beta-2 - metabolism

Culture Media, Conditioned

Animals

Cyclic GMP - metabolism

Receptors, Neurotransmitter - metabolism

Details

Title: Subtitle: Signaling of rat Frizzled-2 through phosphodiesterase and cyclic GMP
Creators: Adriana Ahumada - Department of Molecular Pharmacology, Diabetes and Metabolic Diseases Research Center, University Medical Center, SUNY-Stony Brook, Stony Brook, NY 11794-8651, USA
Diane C Slusarski
Xunxian Liu - Stony Brook University
Randall T Moon
Craig C Malbon
Hsien-yu Wang
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.298(5600), pp.2006-2010
DOI: 10.1126/science.1073776
PMID: 12471263
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Publisher: United States
Grant note: T32-DK07521 / NIDDK NIH HHS
Language: English
Date published: 12/06/2002
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9983991958602771

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