Figure 1.

The Wnt signaling pathway. The blue pathway is the canonical Wnt/β-catenin pathway. Wnts binding to its receptors from Fzd family stimulates the canonical pathway. The multi-protein complex is then inhibited and GSK3β is phosphorylated to an inactive form, leading to a block in β-catenin phosphorylation. Thus, cytoplasmic β-catenin is transported into the nucleus, binding to the promoter region of target genes with TCF/LEF. The green pathway is one non-canonical pathway, also called the Wnt/PCP pathway. Activation of the Wnt/PCP pathway requires the Wnt ligands (WNT4, WNT5A, and WNT11) to bind to the Fzd receptor without LRP 5/6 co-receptor prior to the activation of the Dsh/Dvl protein. Downstream RhoA and JNK cascades are then initiated. The orange pathway is the other non-canonical pathway, called the Wnt/Ca²⁺ pathway. Binding Wnt ligands to the Fzd receptor promotes Dvl recruitment in complexes with heterotrimeric G-proteins. This activates PLC, resulting in inositol IP3 generation and subsequent Ca²⁺ release. The increased intracellular Ca²⁺ concentration activates Ca²⁺-dependent enzymes, such as CamkⅡ. The yellow proteins are endogenously secreted Wnt antagonists.