Frizzleds and WNT/β-catenin signaling--The black box of ligand-receptor selectivity, complex stoichiometry and activation kinetics
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
26003275
DOI
10.1016/j.ejphar.2015.05.031
PII: S0014-2999(15)30015-7
Knihovny.cz E-resources
- Keywords
- Canonical signaling, Class Frizzled, GPCR, LRP5/6, Receptor complex,
- MeSH
- Frizzled Receptors chemistry metabolism MeSH
- Kinetics MeSH
- Humans MeSH
- Ligands MeSH
- Protein Multimerization MeSH
- Wnt Signaling Pathway * MeSH
- Substrate Specificity MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Frizzled Receptors MeSH
- Ligands MeSH
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.
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