Figure 1.

Overview of the Wnt signaling pathway. (A) In the canonical Wnt pathway, secreted Wnt ligands (usually Wnt3A and Wnt1) bind to Frizzled (FZD) receptors and LRP co-receptors. These receptors are then activated via CK1 and GSK3B mediated phosphorylation, which further recruits Dishevelled (DVL) to the plasma membrane and initiates activation. The DVL signalosome results in sequestration and inhibition of β-catenin destruction complex (Axin and APC) allowing stabilized β-catenin levels in the cytoplasm to increase. β-Catenin translocates into the nucleus where it forms an active complex with lymphoid enhancer factor (LEF), T-cell factor (TCF), and other histone-modifying co-activators such as CBP/p300 and BCL9, resulting in transcriptional activation (as represented by red arrow) of Wnt target genes which in turn causes an increase in cellular processes such as cell proliferation and differentiation and stem cell renewal. (B) In the Wnt/PCP pathway, Wnt ligands bind to FZD and co-receptors such as ROR1/2 and recruit DVL to the plasma membrane. DVL interacts with small GTPases such as RHO and RAC to further trigger activation of JNK. This results in activation of cytoskeletal rearrangements by transcriptional responses via JUN and ATF2 (activating transcription factor). (C) The Wnt/Ca²⁺ pathway is initiated by Wnt-FZD-ROR complex and G-protein-triggered phospholipase C (PLC) activity that results in intracellular Ca²⁺ influx. This further activates CDC42 and triggers calcium-dependent cell movement and polarity via various transcriptional responses (red arrow).