Figure 2.

Schematic diagram of the simplified phosphorylation-mediated regulation of the core Wnt/β-catenin pathway components. Phosphorylation of LRP6 at T1479 by CK1γ and at S1490 by GSK3 and Grk5/6 promotes Wnt signaling. Dvl phosphorylation mediated by RIPK4 and CK1ϵ is essential for Wnt signaling. Phosphorylation of Axin at S497/S500 by GSK3 is suppressed by Wnt ligand, resulting in reduced association with LRP6 and β-catenin. C-terminal phosphorylation of β-catenin by PKA inhibits its ubiquitination and thus promotes β-catenin signaling activity. TNIK phosphorylates TCF4 to activate its transcriptional activity. NLK and HIPK2 phosphorylate TCF/LEF factors to inhibit their interaction with DNA.