Fig. 1. The three Wnt signalling pathways and their main components. (A) The canonical ß-catenin pathway is initiated by Wnt binding to Fz/Lrp, which activates Dvl, preventing ß-catenin phosphorylation through the Apc-Axin-Gsk3ß complex. ß-Catenin accumulates in the cytoplasm and translocates to the nucleus, where it activates transcription in association with Tcf. Downstream of Gsk3ß, a divergent pathway controls Map1B phosphorylation. The proposed Wnt-Ryk-Fz complex may function through the same pathway. (B) In the planar cell polarity (PCP) pathway, the binding of Wnt to Fz activates Dvl, which then signals either through Daam1, activating the small Rho GTPase, or through the small Rac GTPase, which in turn leads to JNK activation. Both GTPases then induce changes in the cytoskeleton. (C) In the the Wnt/calcium pathway, Wnt-Fz binding triggers PLC activation, which then hydrolyzes PIP2, generating IP3 and DAG. IP3 leads to the release of intracellular calcium, which activates the calcium/calmodulin dependent protein kinase II (CamKII) and PKC.,ß,, G-protein subunits; Apc, adenomatous polyposis coli; CamKII, calcium/calmodulin-dependent protein kinase II; Daam1, dishevelled associated activator of morphogenesis 1; DAG, diacylglycerol; Dvl, dishevelled; Fz, Frizzled receptor; Gsk3ß, glycogen synthetase kinase 3; IP3, inositol 1,4,5-trisphosphate receptor; JNK, jun kinase; Lrp, low-density lipoprotein receptor-related protein; Map1B, microtubule-associated protein 1B; NF-AT, nuclear factor of activated T cells; PIP2, phosphatidylinositol-4,5-bisphosphate; PKC, protein kinase C; PLC, phospholipase C; Rok, Rho kinase; Ryk, receptor-like tyrosine kinase; Tcf, T-cell factor.