Fig. 1

The Wnt/β-catenin signaling pathway. In the Wnt-off state, defined by the absence of an active Wnt ligand, β-catenin is phosphorylated by the destruction complex (formed from the two kinases Gsk3 and Ck1, the scaffolding protein Axin, and the tumor suppressor Apc) and degraded by the ubiquitin-proteasome pathway. In the Wnt-on state, active Wnt ligands interact with the Fz receptors and the Lrp5/6 coreceptor. Phosphorylation of Lrp5/6 by Gsk3 and Ck1 recruits Dvl and Axin to the receptor complex and hence inhibits the destruction complex. This, in turn, inhibits β-catenin phosphorylation and stabilizes β-catenin in the cytoplasm. β-catenin is then translocated into the nucleus, by a complex including Fam53b/Smp, and regulates target gene expression with the Tcf/Lef transcription factors. Many modulators including the inhibitors sFrps and Wif are known to tightly regulate the signaling cascade