A Protective Role of Canonical Wnt/β-Catenin Pathway in Pathogenic Bacteria-Induced Inflammatory Responses

Figure 1

Canonical Wnt/β-catenin pathway in mammals. (a) Under resting conditions, the cytosolic β-catenin is phosphorylated by GSK3β in a “destruction complex” consisting of AXIN, APC, CK1, and GSK3β, resulting in its ubiquitination and degradation, thereby inhibiting Wnt signaling and disrupting the formation of adherens junction (AJ) by making β-catenin unavailable (Wnt Off). (b) Upon Wnt ligand binding to FZD and LRP5/6, an adaptor protein Dvl/Dsh is recruited and phosphorylated. Phosphorylated Dvl/Dsh then inactivates GSK3β, allowing cytosolic retention of β-catenin, from where it can interact with E-cadherin at the cell membrane to enhance cellular adhesion. The accumulated and nuclear translocation of β-catenin subsequently forms a complex with TCF/LEF proteins by removing transcriptional repressors (e.g., Groucho), initiating the transcription of Wnt target genes (Wnt On).