Fig. 2.

The canonical WNT/β-catenin pathway. WNT (−). Under resting condition, the cytoplasmic β-catenin is bound to its destruction complex, consisting of APC, AXIN and GSK-3β. After CK-1 phosphorylates on Ser45 residue, β-catenin is further phosphorylated on Thr41, Ser37, and Ser33 residues by GSK-3β. Then, phosphorylated β-catenin is degraded into the proteasome. Therefore, the cytosolic level of β-catenin is kept low in the absence of WNT ligands. If β-catenin is not present in the nucleus, the TCF/LEF complex cannot activate the target genes. DKK1 inhibits the WNT/β-catenin pathway by binding to WNT ligands or LRP5/6. WNT (+). When WNT ligands bind to both FZD and LRP5/6, DSH is recruited and phosphorylated by FZD. Phosphorylated DSH in turn recruits AXIN, which dissociates the β-catenin destruction complex. Therefore, β-catenin escapes from phosphorylation and subsequently accumulates in the cytosol. The accumulated cytosolic β-catenin goes into the nucleus, where it binds to TCF/LEF and activates the transcription of target genes