Figure 1. Wnt signalling pathway. Before binding of Wnt proteins to the frizzled receptors, porcupine is likely to be required in the secretory pathway. Proteoglycans in the extracellular matrix can bind to Wnt proteins and are likely to modulate Wnt signalling by limiting diffusion of Wnt proteins. In addition, several secreted molecules, including FRPs, cerberus and WIFs bind to Wnt proteins and modulate Wnt activities. Another secreted molecule, dickkopf (Dkk), antagonizes Wnt signalling although it is not clear whether this protein binds to Wnt directly. The Wnt signal leads to inactivation of a serine/threonine kinase, glycogen synthase kinase 3 (GSK-3), through a cytoplasmic protein, disheveled (dsh), and, in turn, inactivation of GSK-3 causes accumulation of a cytosolic pool of -catenin. In the absence of Wnt signal, phosphorylated -catenin is rapidly degradated through the ubiquitin pathway. The cytoplasmic -catenin forms a high molecular weight complex with axin, which acts as a negative regulator of Wnt pathway, and APC (adenomatous polyposis coli) proteins. Stabilized -catenin binds with transcription factors TCF/Lef-1. This complex regulates expression of target genes in the nucleus. TCF can also bind to groucho and CBP, repressing transcription in opposition to Wnt signal.