Review Article

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

Figure 2

Noncanonical Wnt signaling pathway (β-catenin-independent Wnt signaling pathway). Noncanonical Wnt ligand (such as the Wnt5a, a typical noncanonical Wnt) binds to its receptor (Fzd) and coreceptor (Ror1/2) and triggers the noncanonical signaling cascades, which includes the Wnt/Calcium (Ca2+) and Wnt/planar cell polarity (PCP) pathways. In the Wnt/Ca2+ pathway (left panel), Wnt protein binds to Fzd and Ror2 receptor and leads to activate G proteins, resulting in enhancing the intracellular calcium levels, or decreases cGMP; the calcium/calmodulin-dependent protein kinase II (CaMKII) or protein kinase C (PKC) was then activated. In the Wnt/PCP pathway (right panel), Wnt proteins bind to Fzd receptors on the cell surface followed by activating Rho/Rac small GTPase and Jun N-terminal kinase (JNK) to assist with cytoskeletal organization and gene expression.