Figure 3.

WNT/β‐catenin signalling pathway. (A) In the absence of WNT ligands, β‐catenin is trapped in a destruction complex formed by Axin, APC and GSK3β and phosphorylated in specific residues encoded by exon 3 of CTNNB1. This results in rapid degradation of β‐catenin and, consequentially, the repression of target genes brought about by the interaction of TCF/LEF1 with co‐repressors [e.g. groucho (Gro)/TLE family members]. (B) Binding of WNT ligands to the Frizzled (FZD) receptors and ist co‐receptors LRP leads to the activation of dishevelled (DVL) and recruitment to the cytoplasmic membrane of both DVL and Axin. This causes the dysruption of the destruction complex, releasing β‐catenin, which cannot be efficiently phosphorylated or degraded. The stabilisation of β‐catenin results in increased cytoplasmic protein levels and eventually nuclear translocation, where its interaction with TCF/LEF1 factors mediates the expression of target genes oft he pathway. (C) Expression of a stable form of β‐catenin lacking the amino acids encoded by exon 3 of CTNNB1 (small red circle in BCAT) results in protein stabilisation as mutant β‐catenin cannot be properly phosphorylated or degraded. This causes the activation of the WNT/β‐catenin pathway in a cell‐autonomous manner in the absence of WNT ligands. (Figure courtesy of Dr C. L. Andoniadou.)