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Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch


DURING neurogenesis in Drosophila, groups of equipotential, neurally competent cells choose between epidermal and neural fates1–4. Notch, a phylogenetically conserved transmembrane protein5–9, may act as a receptor4,10 in a lateral signalling pathway in which a single neural precursor is chosen from each group and the neural fate of the other cells is inhibited, causing them to differentiate into epidermis11–13. Possible intracellular transduction events mediating signals from Notch are, however, unknown, shaggy is also required for the lateral signal4,14 and encodes serine/threonine protein kinases15,16 with homology to the glycogen synthase kinase-3 (GSK-3) enzymes17 that act in signal transduction pathways in vertebrates17. We report here that, in transgenic flies, GSK-3/β can substitute for shaggy, and we also present a study of epistatic relationships between shaggy and gain and loss of function alleles of Notch. The results indicate that shaggy/GSK-3 is part of a signalling pathway downstream of Notch

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Ruel, L., Bourouis, M., Heitzler, P. et al. Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. Nature 362, 557–560 (1993).

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