Review Article

Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

Figure 1

Canonical Wnt signaling pathway (β-catenin-dependent Wnt signaling pathway). In the absence of Wnt ligand(s), cytoplasmic β-catenin is targeted for phosphorylation, by a multiprotein complex comprising Axin, adenomatous polyposis coli (APC), the glycogen synthase kinase 3β (GSK3β), and casein kinase 1α (CK1α). The phosphorylated form of β-catenin is recognized by an E3 ubiquitin ligase (β-TrCP) and then targeted to proteasomal degradation, resulting in low cytosolic levels (left panel); in the presence of Wnt ligand(s), Wnt ligand binds to the Fzd and LRP receptors, and this binding triggers the signaling and activates the Dvl; the activation of Dvl inhibits the GSK-3β and results in destructing the multiprotein complex which stabilizes and leads to the intracellular accumulation of β-catenin in the cytoplasm; accordingly the active β-catenin translocates to the nucleus, where it acts as a transcriptional coactivator with TCF/LEF to activate Wnt-responsive target genes (right panel).