fig4

Figure 4. Wnt/β-catenin signaling pathways. In the canonical (β-catenin-dependent) pathway, Wnt ligand binds to its Frizzled receptor and co-receptor LRP 5/6. Upon activation, the signal is transduced and DVL1 gets activated which in turn inhibits GSK-3β and CK1 activity. This inhibition results in accumulation of intracellular β-catenin and its translocation into the nucleus. β-catenin acts as a transcriptional regulator along with LEF1 and TCF4. This transcriptional complex induces the expression of Wnt target genes that promote cell proliferation and differentiation. In the non-canonical (β-catenin-independent) pathway, Wnt ligands binds to its Frizzled receptor and triggers DLV1 to activate the cGMP-specific PDE and PLC. Activated PLC cleaves the membrane-bound PIP2 into IP3 and DAG. IP3 induces intracellular Ca²⁺ release from the endoplasmic reticulum. The resulting Ca²⁺ activates both CaMKII and calcineurin. CaMKII activates transcription factor NF-κB and calcineurin activates transcription factor NFAT. Cytoplasmic levels of β-catenin are kept low by downstream kinases of calcineurin NLK and TAK1. Modified from Tompa et al.^[92]