THE DISHEVELLED PROTEIN IS MODIFIED BY WINGLESS SIGNALING IN DROSOPHILA

Wingless (Wg) is an important signaling molecule in the development of Drosophila, but little is known about its signal transduction pathway . Genetic evidence indicates that another segment polarity gene, dishe velled (dsh) is required for Wg signaling. We have recently developed a cell culture system for Wg protein activity, and using this in vitro system as well as intact Drosophila embryos, we have analyzed biochem ical changes in the Dsh protein as a consequence of Wg signaling. We f ind that Dsh is a phosphoprotein, normally present in the cytoplasm. W g signaling generates a hyperphosphorylated form of Dsh, which is asso ciated with a membrane fraction. Overexpressed Dsh becomes hyperphosph orylated in the absence of extracellular Wg and increases levels of th e Armadillo protein, thereby mimicking the Wg signal. A deletional ana lysis of Dsh identifies several conserved domains essential for activi ty, among which is a so-called GLGF/DHR motif. We conclude that dsh, a highly conserved gene, is not merely a permissive factor in Wg signal ing but encodes a novel signal transduction molecule, which may functi on between the Wg receptor and more downstream signaling molecules.