Figure 8. Schematic representation of mechanisms regulating β-catenin and ABC.

The cellular level of β-catenin is very tightly regulated by phosphorylation. Phosphorylation of β-catenin by glycogen synthase kinase-3beta (GSK-3β) results in its degradation. Prevention of phosphorylation upon activation of the Wnt pathway inhibits phosphorylation of β-catenin and stabilizes the protein which results in an increase of its levels inside cells. In this manuscript we show that while the canonical Wnt pathway stabilizes cellular levels of β-catenin it does not regulate cellular ABC levels. ABC levels are regulated by the PI3K pathway via activation of PP2A which then partially dephosphorylates β-catenin at serine 37 and threonine 41 to generate ABC and enable its transcriptional properties.