The canonical Wnt signaling pathway (IMAGE)
Caption
The canonical Wnt signaling pathway. The left panel (A) demonstrates the activated Wnt signaling cascade, while the right side portrays the inhibited Wnt signaling cascade. Wnt binds to the Fz receptor and LRP5/6 co-receptor. This activates Dvl to cause the dissociation of Axin from the destruction complex, causing β-catenin to be stabilized and enter the nucleus. β-Catenin can then displace the inhibitory TLE/Groucho complexes, enabling TCF/LEF to transcribe the target genes. PP2A can also enhance Wnt signaling by dephosphorylating β-catenin, APC, and Axin. The result is the preservation of β-catenin by preventing ubiquitination and proteasomal breakdown. In the absence of Wnt signaling (B), the destruction complex breaks down β-catenin and inhibits gene transcription. Several other proteins also contribute to the inhibition of Wnt signaling. Dkk1 associates with Krm1 or Krm2 and LRP5/6, causing endocytosis of the LRP5/6 co-receptor. Wise/sclerostin binds to LRP5/6 to inhibit proper Wnt association with the coreceptor. xCer-L and WIF-1 both bind to Wnt ligands to inhibit signaling. IGFBP-4 functions as a competitive inhibitor of Wnt signaling by associating with LRP6 and Fz8, while sFRPs complex with Fz receptors to prevent Wnt ligand binding. The illustration was inspired by and created in BioRender.
Credit
Kevin Qin, et al.
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License
CC BY-NC-ND