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

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Publikace nespadá pod Filozofickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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SCHULTE Gunnar

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj European Journal of Pharmacology
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://www.sciencedirect.com/science/article/pii/S0014299915300157
Doi http://dx.doi.org/10.1016/j.ejphar.2015.05.031
Obor Genetika a molekulární biologie
Klíčová slova Receptor complex; Canonical signaling; GPCR; LRP5/6; Class Frizzled
Popis 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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