Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster

Modulation of the Ras/MAPK signalling pathway by the redox function of selenoproteins in Drosophila melanogaster
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DOI:
10.1006/dbio.2001.0389
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发表时间:
2001-10-01
影响因子:
2.7
通讯作者:
Corominas, M
Corominas, M
中科院分区:
生物学3区
文献类型:
--
作者:
Morey, M;Serras, F;Corominas, M

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活性氧(ROS)的调节在信号转导途径中起着关键作用。硒蛋白控制细胞的氧化还原平衡。我们已经研究了如何改变的氧化还原平衡所造成的patufet(seld(ptuf)),一个无效突变的果蝇硒磷酸合成酶1(sps1)基因,编码的SelD酶的硒蛋白生物合成,影响Ras/MAPK信号通路。selD(ptuf)突变主要抑制眼睛和翅膀中的表型,所述表型由Ras/MAPK盒的超活化以及果蝇EGF受体(DER)和Sevenless(Sev)受体酪氨酸激酶(RTK)的活化形式引起,所述受体酪氨酸激酶(RTK)分别在眼睛和翅膀中发出信号。在Wnt、Notch、胰岛素-Pi 3 K和DPP信号通路中,未观察到与致敏条件的主导相互作用。我们目前的假设是,硒蛋白选择性地调节Ras/MAPK信号通路,通过其抗氧化功能。这进一步得到了以下事实的支持:由过氧化氢酶无定形Cat(nI)等位基因引起的ROS的硒蛋白非依赖性增加也降低了Ras/MAPK信号传导。在这里,我们提出了第一个证据的作用,细胞内的氧化还原环境中的信号转导通路在果蝇作为一个整体的有机体。(C)北京:科学出版社.
Modulation of reactive oxygen species (ROS) plays a key role in signal transduction pathways. Selenoproteins act controlling the redox balance of the cell. We have studied how the alteration of the redox balance caused by patufet (seld(ptuf)), a null mutation in the Drosophila melanogaster selenophosphate synthetase 1 (sps1) gene, which codes for the SelD enzyme of the selenoprotein biosynthesis, affects the Ras/MAPK signalling pathway. The selD(ptuf) mutation dominantly suppresses the phenotypes in the eye and the wing caused by hyperactivation of the Ras/MAPK cassette and the activated forms of the Drosophila EGF receptor (DER) and Sevenless (Sev) receptor tyrosine kinases (RTKs), which signal in the eye and wing, respectively. No dominant interaction is observed with sensitized conditions in the Wnt, Notch, Insulin-Pi3K, and DPP signalling pathways. Our current hypothesis is that selenoproteins selectively modulate the Ras/MAPK signalling pathway through their antioxidant function. This is further supported by the fact that a selenoprotein-independent increase in ROS caused by the catalase amorphic Cat(nI) allele also reduces Ras/MAPK signalling. Here, we present the first evidence for the role of intracellular redox environment in signalling pathways in Drosophila as a whole organism. (C) 2001 Academic Press.