The Wnt/β-catenin pathway is activated when a Wnt ligand binds to a seven-pass transmembrane Frizzled (Fz) receptor and its co-receptor, low-density lipoprotein receptor related protein 6 (LRP6) or its close relative LRP5. The formation of a likely Wnt-Fz-LRP6 complex together with the recruitment of the scaffolding protein Dishevelled (Dvl) results in LRP6 phosphorylation and activation and the recruitment of the Axin complex to the receptors. These events lead to inhibition of Axin-mediated β-catenin phosphorylation and thereby to the stabilization of β-catenin, which accumulates and travels to the nucleus to form complexes with TCF/LEF and activates Wnt target gene expression.Two distinct classes of Wnt inhibitors are the Dickkopf (Dkk) family and the Wise/SOST family. Dkk proteins, exemplified by Dkk1, are LRP5/6 ligands/antagonists and are considered specific inhibitors for Wnt/β-catenin signaling.


Bryan T. MacDonald et al.Dev Cell. 2009 Jul; 17(1): 9–26.