The Wnt- β-catenin / -canonical pathway

Wnt Pathway
Wnt Pathway
  • Ligand: Wnt factors, Receptor: Frizzled
  • Cascade:
    1. Wnt activates Frizzled receptor.
    2. Glycogen synthase kinase-3β (GSK-3β) is suppressed (via dishevelled).
    3. GSK-3β cannot phosphorylate β-catenin.
      • without active frizzled, β-catenin will form a multiprotein complex with Apc and axin. This protein complex helps to bring β-catenin together with GSK-3β for phosphorylation.
      • When β-catenin is phosphorylated, it subsequently is ubiquitylated, what leads to rapid degradation of β-catenin.
    4. β-catenin is not degraded
    5. β-catenin accumulates in cytoplasm and nucleus
    6. Two distinct effects:
      • in nucleus, β-catenin associates with Tcf/Lef transcription factors which enable the expression of genes (e.g. Cyclin D1, Myc), that drive increased proliferation and prevent differentiation. This way the canonical wnt pathway mainly contributes to the stem-cell phenotype.
      • At the cell membrane, β-catenin in involved in the formation of adherens junction, since β-catenin together with p120 and alpha-catenein establishes the linkage between cadherin and the actin cytosceleton.