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Eur J Pharmacol. 2015 Sep 15;763(Pt B):191-5. doi: 10.1016/j.ejphar.2015.05.031. Epub 2015 May 21.

Frizzleds and WNT/β-catenin signaling--The black box of ligand-receptor selectivity, complex stoichiometry and activation kinetics.

Author information

1
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.

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.

KEYWORDS:

Canonical signaling; Class Frizzled; GPCR; LRP5/6; Receptor complex

PMID:
26003275
DOI:
10.1016/j.ejphar.2015.05.031
[Indexed for MEDLINE]

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