The Frizzled family of unconventional G-protein-coupled receptors

Faculty of Science, Masaryk University, Brünn, South Moravian, Czech Republic
Trends in Pharmacological Sciences (Impact Factor: 11.54). 11/2007; 28(10):518-25. DOI: 10.1016/
Source: PubMed


The Frizzled (FZD) family of receptors is critically involved in embryogenesis, and there is substantial evidence that members of this family also regulate tissue homeostasis in many different organs in the adult. FZD receptors have seven transmembrane-spanning domains and are activated by the WNT family of lipoglycoproteins. Many aspects of FZD signal transduction and pharmacology are still unclear. In this review, we summarize recent advances and some of the key questions about the molecular pharmacology of FZDs, FZD-associated proteins and signal transduction. We also discuss what little is known about the pharmacological binding profiles and the degree of selectivity of WNTs and other extracellular ligands for FZDs. Finally, we focus on signaling events that occur as a direct consequence of FZD activation, signaling via the central phosphoprotein Dishevelled (DVL) and FZD coupling to heterotrimeric G proteins. Here, we outline the current state of knowledge on FZDs and FZD signal transduction and pinpoint aspects of debate and future directions.

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Available from: Gunnar Schulte
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    • "Nineteen Wnt genes have been identified in the vertebrate genome, all of which signal through the seven-transmembrane-domain Frizzled (FZD) receptors (Schulte et al, 2007). Signaling events occur as the direct consequence of FZD activation, via the phosphoprotein dishevelled (DVL). "
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    • "Frizzled4 (Fz4) belongs to the family of Frizzled cell surface receptors that are involved in a variety of biological processes during development as well as in adult life1112. Fz4 displays the structural landmarks observed in G protein-coupled receptors1112: an ectosolic N-Terminus, seven hydrophobic transmembrane segments, three intracellular and extracellular loops and a cytosolic C-terminal tail13. Two PDZ binding motives are located one internally and one at the C-terminus of Fz4. "
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    • "Dfz2 groups closely with FZD5/8 and fz/Dfz1 with FZD3/6. The Hedgehog (another family of secreted signaling protein) pathway protein Smoothened (SMO) is distantly related to FZD (Schulte and Bryja 2007 "
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