Figure 4

A schematic diagram for the Wnt signaling pathway. (a) The canonical Wnt/β-catenin pathway. Canonical Wnt signaling requires the Frizzled (Fz) and low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) co-receptors to activate Dishevelled (Dsh). Then Dsh inhibits the activity of the β-catenin destruction complex (adenomatous polyposis coli (APC), axin, and glycogen synthase kinase-3 (GSK-3)), which phosphorylates β-catenin in the absence of the ligands. β-Catenin is stabilized and translocated to the nucleus, where it recruits transactivators to high mobility group (HMG)-box DNA-binding proteins of the lymphoid enhancer factor/T cell factor (LEF/TCF) family. (b) The noncanonical Wnt signaling pathway. Noncanonical Wnt signaling requires Frizzled receptors and the proteoglycan co-receptor Knypek. In this pathway, Dsh localizes to the cell membrane through its DEP domain. A main branch downstream of Dsh involves the small GTPases of the Rho family. Dsh activation of Rho requires the bridging molecule Daam1. Dsh can also stimulate calcium flux and the activation of the calcium-sensitive kinases protein kinase C (PKC) and calmodulin-dependent protein kinase II (CanKII). At the end, the activation of this pathway induces the complex and dynamic cellular response.