title: Frizzleds and WNT/β-catenin signaling--The black box of ligand-receptor selectivity, complex stoichiometry and activation kinetics.
abstract: The lipoglycoproteins of the mammalian WNT family induce β-catenin-dependent signaling through interaction with members of the Class Frizzled receptors and LDL receptor-related protein 5/6 (LRP5/6) albeit with unknown selectivity. The 10 mammalian Frizzleds (FZDs) are seven transmembrane (7TM) spanning receptors and have recently been classified as G protein-coupled receptors (GPCRs). This review summarizes the current knowledge about WNT/FZD selectivity and functional selectivity, the role of co-receptors for signal specification, the formation of receptor complexes as well as the kinetics and mechanisms of signal initiation with focus on WNT/β-catenin signaling. In order to exploit the true therapeutic potential of WNT/FZD signaling to treat human disease, it is clear that substantial progress in the understanding of receptor complex formation and signal specification has to precede a mechanism-based drug design targeting WNT receptors.
authors.affiliation: Department of Physiology & Pharmacology, Section of Receptor Biology & Signaling, Karolinska Institutet, S-17177 Stockholm, Sweden; Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic. Electronic address: gunnar.schulte@ki.se.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Schulte
mesh_terms: D000818:Animals; D051157:Frizzled Receptors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D055503:Protein Multimerization; D013379:Substrate Specificity; D060449:Wnt Signaling Pathway
chemical_list: D051157:Frizzled Receptors; D008024:Ligands
keywords: Canonical signaling; Class Frizzled; GPCR; LRP5/6; Receptor complex