Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 763, Issue -, Pages 191-195Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2015.05.031
Keywords
Receptor complex; Canonical signaling; GPCR; LRP5/6; Class Frizzled
Categories
Funding
- Marie Curie ITN WntsApp [608180]
- Karolinska Institutet
- Swedish Research Council [K2008-68P-20810-01-4, K2008-333 68X-20805-01-4, K2012-67X-20805-05-3]
- Swedish Cancer Society [CAN 2008/539, 2011/690, 2014/659]
- Knut and Alice Wallenberg Foundation [KAW2008.0149]
- Engkvist Foundations
- Czech Science Foundation (GACR) [13-32990S]
- European Regional Development Fund (KI-MU) [CZ.1.07/2.3.00/20.0180]
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The lipoglycoproteins of the mammalian WNT family induce beta-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/beta-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. (C) 2015 Elsevier B.V. All rights reserved
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