Wnt canonical pathway. (a) In the absence of a Wnt ligand, the cytoplasmic β-catenin is degraded by the "destruction complex". In this complex, Axin acts as an scaffold protein, which APC, GSK-3β and CK1α bind to facilitate the sequential phophorylation of β-catenin by kinase CK1α and GSK-3β. Accordingly, phosphorylated β-catenin is recognized by β-TrCP and constantly degraded by the ubiquitin-proteasome pathway. (b) Upon ligation of Wnts to their receptors composed of Fz proteins and LRP5/6, the cytoplasmic protein Dvl is recruited, phosphorylated and activated. Activation of Dvl induces the dissociation of GSK-3β from Axin and leads to the inhibition of GSK-3β. Next, the phosphorylation and degradation of β-catenin is inhibited as a result of the inactivation of the "destruction complex". Subsequently, stabilized β-catenin translocates into the nucleus. Nuclear β-catenin is the ultimate effector, binding to Tcf/Lef transcription factors to lead to changes in different target gene expressions.