Regulation of the protein kinase activity of Shaggy(Zeste-white3) by components of the wingless pathway in Drosophila cells and embryos

The protein-serine kinase Shaggy(Zeste-white3) (Sgg(Zw3)) is the Drosophila homolog of mammalian glycogen synthase kinase-3 and has been genetically i mplicated in signal transduction pathways necessary for the establishment o f patterning. Sgg(Zw3) is a putative component of the Wingless (Wg) pathway , and epistasis analyses suggest that Sgg(Zw3) function is repressed by Wg signaling. Here, we have investigated the biochemical consequences of Wg si gnaling with respect to the Sgg(Zw3) protein kinase in two types of Drosoph ila cell lines and in embryos. Our results demonstrate that Sgg(Zw3) activi ty is inhibited following exposure of cells to Wg protein and by expression of downstream components of Wg signaling, Drosophila frizzled 2 and dishev elled. Wg-dependent inactivation of Sgg(Zw3) is accompanied by serine phosp horylation. We also show that the level of Sgg(Zw3) activity regulates the stability of Armadillo protein and modulates the level of phosphorylation o f D-Axin and Armadillo. Together, these results provide direct biochemical evidence in support of the genetic model of Wg signaling and provide a mode l for dissecting the molecular interactions between the signaling proteins.