FIGURE 1.

Wnt signaling pathways. (A) Canonical Wnt/ß-catenin pathway OFF: In the absence of Wnt binding to Frizzled (Fz) receptors and LRP5/6 co-receptors, ß-catenin interacts with the destruction complex (CK1, GSK3β, Axin1 and APC), resulting in its phosphorylation by Gsk3ß and CK1 and its subsequent degradation by the proteasome. (B) Canonical Wnt/ß-catenin pathway ON: When a Wnt ligand binds to LRP5/6 and Fz receptors, the scaffold protein Disheveled (Dvl) recruits Axin1 and the kinases CK1 and GSK3ß to the membrane, disrupting the destruction complex and impairing ß-catenin phosphorylation and degradation. ß-catenin accumulates in the cytoplasm and subsequently translocates to the nucleus, where it acts as an activator of TCF/LEF-mediated transcription of Wnt target genes. (C) The Planar Cell Polarity (PCP) pathway: The PCP does not require LRP5/6 and is ß-catenin-independent. When Wnts bind to Fz receptors, Dvl is activated, resulting in increased activation of ROCK and JNK through the small GTPases RhoA and Rac1, respectively. Changes in ROCK activity induce actin remodeling, and JNK activation can promote gene transcription via Jun phosphorylation. The palmitate group in Wnt ligands is indicated as a yellow tail. CK1, casein kinase 1; GSK3ß, glycogen synthase kinase 3β; Axin1, axis inhibition protein 1; APC, adenomatous polyposis coli; TCF, T-cell factor; LEF, lymphocyte-enhancer-binding factor; Rock, Rho associated coiled-coil-containing protein kinase 1; RhoA, RAS homolog gene-family member A; JNK, Jun N-terminal kinase.