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. 2021 May 14;296:100782. doi: 10.1016/j.jbc.2021.100782

Figure 1.

Figure 1

Overview of the canonical Wnt/β-catenin signaling pathway.Top, WNT is lipid modified by PORCN in the endoplasmic reticulum (ER) and transported to the Golgi complex, where WLS palmitoleoylates and chaperones WNT to the plasma membrane. Left, β-catenin signaling is inhibited without WNT present (“WNT OFF”). FZD is removed from the cell membrane by RNF43/ZNRF3 binding through DVL. The β-catenin concentration is kept low by an intracellular multiprotein destruction complex that includes APC, axin, CK1, and glycogen synthase kinase 3 (GSK3), which facilitates the GSK3-dependent phosphorylation of β-catenin that targets it for ubiquitin-dependent proteolysis. This continuous degradation is vital in preventing the accumulation and nuclear translocation of β-catenin. Right, WNT causes the accumulation of β-catenin and activates signaling (“WNT ON”). When a WNT ligand engages the receptor complex, the C terminus of LRP5/6 is phosphorylated, creating a binding site for axin, resulting in inhibition of the destruction complex and GSK3 activity, allowing cytoplasmic levels of β-catenin to increase. β-Catenin subsequently translocates into the nucleus and complexes with LEF/TCF proteins and other co-factors to activate transcription of target genes. CK1, casein kinase 1; DVL, Dishevelled; LRP5, low-density lipoprotein receptor-related proteins 5; LRP6, low-density lipoprotein receptor-related proteins 6; RNF43, Ring finger protein 43; ZNRF3, Zing and ring finger 3.