Fig. 1. Outline of Wnt/ß-catenin signaling. (A) In the absence of Wnt, ß-catenin (ß-cat) is phosphorylated by a complex containing GSK3. This targets ß-catenin for proteosomal degradation. In the nucleus, members of the T-cell factor (TCF) family of DNA-binding proteins repress Wnt targets, in concert with co-repressors such as Groucho (Gro). (B) Upon Wnt binding to Fz-LRP receptors, a combination of LRP-axin interaction and Dvl phosphorylation (P) blocks the APC-axin-GSK3 complex from phosphorylating ß-catenin. The accumulated ß-catenin then enters the nucleus, where it converts TCF into a transcriptional activator. See the Wnt homepage (http://www.stanford.edu/~rnusse/wntwindow.html) for a more complete description of Wnt signaling components.