301575.fig.001a
(a)
301575.fig.001b
(b)
Figure 1: The Wnt signaling pathway. Wnt binds to the classical receptor Frizzled (Fz) and activates the down-stream signaling pathways. (a) Wnt binds to Fz and its coreceptor and eventually with casein kinase-1 (CK-1) participation, activating the scaffold protein Dishevelled (Dvl). Subsequently this induces the disassembly of the “destruction complex” and leads to the accumulation and the stabilization of β-catenin in the cytosol and its translocation into the nucleus, which promotes target gene expression, such as PPAR-δ, cyclin D-1, GLUT-1, Claudin-3, and Claudin-5. (b) In the planar cell polarity (PCP) pathway, Wnt ligand binds to Fz, which in turn stimulates Dvl with its coreceptor, followed by activation of Rho/Rac small GTPase and c-Jun-N-terminal kinase (JNK), which leads to changes in actin and microtubule reorganization. In the Ca2+ pathway, the intracellular level of Ca2+ is increased by Wnt-receptor interaction via phospholipase-C (PLC), which in turn causes Ca2+ release followed by Ca2+/Calmodulin-dependent protein kinase II (CamK II) and protein kinase C (PKC) activation, which in turn activate the nuclear translocation of transcription factor nuclear factor of activated T cells (NFACT) and cAMP response element-binding protein-1 (CREB) and consequently activate gene transcription.