DROSOPHILA SHAGGY KINASE AND RAT GLYCOGEN-SYNTHASE KINASE-3 HAVE CONSERVED ACTIVITIES AND ACT DOWNSTREAM OF NOTCH

DROSOPHILA SHAGGY KINASE AND RAT GLYCOGEN-SYNTHASE KINASE-3 HAVE CONSERVED ACTIVITIES AND ACT DOWNSTREAM OF NOTCH
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DOI:
10.1038/362557a0
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发表时间:
1993-04-08
期刊:
影响因子:
64.8
通讯作者:
SIMPSON, P
SIMPSON, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
RUEL, L;BOUROUIS, M;SIMPSON, P

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在果蝇的神经发生过程中,等电位的神经活性细胞组在表皮和神经fates 1 -4之间进行选择。Notch是一种遗传学上保守的跨膜蛋白5 -9,可能在侧向信号传导途径中充当受体4,10,其中从每组中选择单个神经前体细胞,并抑制其他细胞的神经命运,使它们分化为表皮11 -13。 然而,可能的细胞内转导事件介导的信号从Notch是未知的。Shaggy也是侧向信号所必需的4,14,并编码丝氨酸/苏氨酸蛋白激酶15,16,其与在脊椎动物中的信号转导途径中起作用的糖原合成酶激酶-3(GSK-3)酶17具有同源性17。我们在这里报告,在转基因果蝇中,GSK-3 β可以取代shaggy,我们还提出了一个研究的shaggy和获得和Notch的功能等位基因的损失之间的上位关系。结果表明,shaggy/GSK-3是Notch下游信号通路的一部分。
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 trans duction 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-3beta 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.