This article is part of the supplement: 12th Joint Meeting of the Signal Transduction Society (STS). Signal Transduction: Receptors, Mediators and Genes
Meeting abstract
The G protein-coupled receptor identity of the frizzled proteins
Cell Communication and Signaling 2009, 7(Suppl 1):A19 doi:10.1186/1478-811X-7-S1-A19
The electronic version of this article is the complete one and can be found online at: http://www.biosignaling.com/content/7/S1/A19
| Published: | 26 February 2009 |
© 2009 Katanaev and Buestorf; licensee BioMed Central Ltd.
Meeting abstract
Receptors of the Frizzled family initiate Wnt ligand-dependent 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 Frizzled-related 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.