Phosphorylation of the fused protein kinase in response to signaling from hedgehog.

Phosphorylation of the fused protein kinase in response to signaling from hedgehog.
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DOI:
10.1073/pnas.93.9.4224
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发表时间:
1996-04
影响因子:
11.1
通讯作者:
Pascal P. Thérond;J. Knight;Thomas B. Kornberg;J. Bishop
Pascal P. Thérond;J. Knight;Thomas B. Kornberg;J. Bishop
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pascal P. Thérond;J. Knight;Thomas B. Kornberg;J. Bishop

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果蝇Hedgehog基因(HH)对发育过程中的细胞构型有短期和长期的影响。Hedgehog的产物是一种分泌蛋白,显然是通过触发细胞内信号途径来发挥作用,但人们对该途径的细节知之甚少。果蝇基因融合(Fu)编码一种丝氨酸/苏氨酸蛋白激酶,遗传学实验表明,该蛋白与刺猬启动的信号传递有关。在这里,我们报告融合蛋白在果蝇胚胎发育过程中被磷酸化,这是刺猬活动的结果。在细胞培养中,融合蛋白的磷酸化反应发生在生物活性形式的刺猬,而不是被激活的蛋白激酶A,它被认为是来自刺猬的信号拮抗剂。这些结果表明,融合蛋白和蛋白激酶A在刺猬的下游发挥作用,但在平行的途径上,最终在远端汇聚到融合。刺猬在细胞培养中信号的重建应该提供进一步了解刺猬的作用机制的途径。
The hedgehog gene (hh) of Drosophila melanogaster exerts both short- and long-range effects on cell patterning during development. The product of hedgehog is a secreted protein that apparently acts by triggering an intra-cellular signaling pathway, but little is known about the details of that pathway. The Drosophila gene fused (fu) encodes a serine/threonine-protein kinase that genetic experiments have implicated in signaling initiated by hedgehog. Here we report that the fused protein is phosphorylated during the course of Drosophila embryogenesis, as a result of hedgehog activity. In cell culture, phosphorylation of fused protein occurs in response to the biologically active form of hedgehog and cannot be blocked by activation of protein kinase A, which is thought to be an antagonist of signaling from hedgehog. These results suggest that fused and protein kinase A function downstream of hedgehog but in parallel pathways that eventually converge distal to fused. The reconstruction of signaling from hedgehog in cell culture should provide further access to the mechanisms by which hedgehog acts.