Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.
Open Access
- 2 September 1996
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 15 (17) , 4526-4536
- https://doi.org/10.1002/j.1460-2075.1996.tb00830.x
Abstract
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.Keywords
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