Fig. 3
From: A new precision medicine initiative at the dawn of exascale computing
The Wnt signaling pathways. In the absence of Wnt signal, the destruction complex constituted by Axin, adenomatosis polyposis coli (APC), and glycogen synthase kinase 3β (GSK3β) leads to phosphorylation of β-catenin by GSK3β in the cytoplasm. The phosphorylated β-catenin is subsequently ubiquitinated by β-TrCP and targeted for proteasomal degradation. The canonical Wnt/β-catenin pathway is activated by upon binding of Wnt to its Frizzled (Frz) receptor and low-density lipoprotein receptor-related protein 6 (LRP6) co-receptor. LRP6 phosphorylated by cyclin-Y/CDK14 complex, GSK3β, and casein kinase 1γ (CK1γ) recruits the destruction complex and Dishevelled (Dsh, Dvl in mammals) to the plasma membrane. Dvl is activated through polymerization, inhibiting the destruction complex. This results in accumulation of unphosphorylated β-catenin in the cytoplasm and its subsequent translocation into the nucleus, leading to cell proliferation. In the non-canonical Wnt/calcium pathway, calmodulin-bound CaMKII (calcium/calmodulin-dependent protein kinase II) negatively regulates the canonical β-catenin/TCF/LEF signaling through phosphorylation of TCF, which inhibits β-catenin/TCF-mediated transcription
