Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.
AUTOR(ES)
Cook, D
RESUMO
The Drosophila gene product Wingless (Wg) is a secreted glycoprotein and a member of the Wnt gene family. Genetic analysis of Drosophila epidermal development has defined a putative paracrine Wg signalling pathway involving the zeste-white 3/shaggy (zw3/sgg) gene product. Although putative components of Wg- (and by inference Wnt-) mediated signalling pathways have been identified by genetic analysis, the biochemical significance of most factors remains unproven. Here we show that in mouse 10T1/2 fibroblasts the activity of glycogen synthase kinase-3 (GSK-3), the murine homologue of Zw3/Sgg, is inactivated by Wg. This occurs through a signalling pathway that is distinct from insulin-mediated regulation of GSK-3 in that Wg signalling to GSK-3 is insensitive to wortmannin. Additionally, Wg-induced inactivation of GSK-3 is sensitive to both the protein kinase C (PKC) inhibitor Ro31-8220 and prolonged pre-treatment of 10T1/2 fibroblasts with phorbol ester. These findings provide the first biochemical evidence in support of the genetically defined pathway from Wg to Zw3/Sgg, and suggest a previously uncharacterized role for a PKC upstream of GSK-3/Zw3 during Wnt/Wg signal transduction.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=452182Documentos Relacionados
- Glycogen synthase kinase-3 enhances nuclear export of a Dictyostelium STAT protein
- Regulation of Serotonin 1B Receptor by Glycogen Synthase Kinase-3
- Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation.
- Expression and characterization of glycogen synthase kinase-3 mutants and their effect on glycogen synthase activity in intact cells.
- Glycogen Synthase Kinase 3 Is an Insulin-Regulated C/EBPα Kinase
