Wnts are secreted glycoproteins that bind to frizzled seven-transmembrane-span receptors. The proteoglycan dally acts as a co-receptor for Wnts. Various secreted factors, such as WIF-1, cerberus (cer) and FrzB, bind to Wnts and block the interaction with frizzled proteins. Dickkopf (Dkk) antagonises Wnt action in an unknown fashion. In Drosophila, secretion of the Wnt homologue, Wingless, depends on the protein Porcupine (PORC).
Intracellularly, Wnt signalling leads to stabilisation of cytosolic β-catenin. In the absence of Wnts, β-catenin is phosphorylated by glycogen synthase kinase 3β (GSK3β), which triggers ubiquitination of β-catenin by βTrCP and degradation in proteasomes. Phosphorylation of β-catenin occurs in a multiprotein complex assembled by the scaffolding protein axin or conductin. In the presence of Wnts, dishevelled (dsh) blocks β-catenin degradation, possibly by recruiting the GSK3β inhibitor GBP to the complex. In certain tumors, mutation of axin, β-catenin or the tumor suppressor APC also lead to stabilisation of...
