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

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• 作者：Gunnar Schulte^a ; ^b ; ^{gunnar.schulte@ki.se" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Receptor complex ; Canonical signaling ; GPCR ; LRP5/6 ; Class Frizzled
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 September 2015
• 年：2015
• 卷：763
• 期：part_PB
• 页码：191-195
• 全文大小：451 K

文摘

The lipoglycoproteins of the mammalian WNT family induce 尾-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/尾-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.