The G protein-coupled receptor identity of the frizzled proteins
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BioMed Central
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Meeting abstract
The G protein-coupled receptor identity of the frizzled proteins VL Katanaev* and S Buestorf Address: University of Konstanz, Department of Biology, Konstanz, Switzerland * Corresponding author
from 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes Weimar, Germany. 29–31 October 2008 Published: 26 February 2009 Cell Communication and Signaling 2009, 7(Suppl 1):A19
doi:10.1186/1478-811X-7-S1-A19
12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Frank Entschladen, Karlheinz Friedrich, Ralf Hass and Ottmar Janssen Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here.This abstract is available from: http://www.biosignaling.com/content/7/S1/A19 © 2009 Katanaev and Buestorf; licensee BioMed Central Ltd.
Receptors of the Frizzled family initiate Wnt liganddependent signal transduction cascades controlling multiple steps in organism development and are highly conserved in animal evolution. Misactivation of the Wnt/ Frizzled signaling underlies many cases of cancerogenesis. Frizzled receptors possess seven transmembrane domains and their signaling depends on trimeric G proteins in various organisms. However, as Frizzled proteins constitute a distinct group within the superfamily of G protein-coupled receptors (GPCR), and as Frizzled signaling can apparently be G protein-independent in some experimental setups, the GPCR nature of Frizzled receptors has been questioned. Here we demonstrate that human Frizzled receptors can directly bind the trimeric Go protein in a pertussis toxin-sensitive manner. Furthermore, addition of Wnt ligands elicits Frizzled-dependent guanine nucleotide exchange on Go. An excess of secreted Frizzledrelated protein, a known antagonist of the Wnt/Frizzled pathways, inhibits Go activation, as does pretreatment of Go with pertussis toxin. These experiments provide a biochemical proof of the GPCR activities of Frizzled receptors. They also establish an in vitro assay of monitoring Frizzled activation by Wnt ligands, applicable for the high-throughput agonist/antagonist screening.
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