Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling

Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling
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DOI:
10.1016/s1534-5807(02)00151-x
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发表时间:
2002-05-01
期刊:
影响因子:
11.8
通讯作者:
Kornfeld, K
Kornfeld, K
中科院分区:
生物学1区
文献类型:
--
作者:
Bruinsma, JJ;Jirakulaporn, T;Kornfeld, K

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C.在Ras介导的信号传导的调节剂的遗传筛选中鉴定了秀丽线虫cdf-1。CDF-1是一种阳离子扩散促进蛋白,其结构和功能与脊椎动物ZnT-1相似。这些蛋白质具有作为Ras途径的正调节剂的进化上保守的功能,并且Ras途径具有响应CDF蛋白的进化上保守的能力。CDF蛋白通过促进Zn 2+流出和降低胞质Zn 2+浓度来调节Ras介导的信号传导,并且胞质Zn 2+负调节Ras介导的信号传导。生理浓度的Zn 2+导致Ras介导的信号传导的显著抑制。这些研究结果表明,Zn 2+负调节信号通路的保守元件,Zn 2+调节对于维持Ras通路的非活性状态是重要的。
C. elegans cdf-1 was identified in a genetic screen for regulators of Ras-mediated signaling. CDF-1 is a cation diffusion facilitator protein that is structurally and functionally similar to vertebrate ZnT-1. These proteins have an evolutionarily conserved function as positive regulators of the Ras pathway, and the Ras pathway has an evolutionarily conserved ability to respond to CDF proteins. CDF proteins regulate Ras-mediated signaling by promoting Zn2+ efflux and reducing the concentration of cytosolic Zn2+, and cytosolic Zn2+ negatively regulates Ras-mediated signaling. Physiological concentrations of Zn2+ cause a significant inhibition of Ras-mediated signaling. These findings suggest that Zn2+ negatively regulates a conserved element of the signaling pathway and that Zn2+ regulation is important for maintaining the inactive state of the Ras pathway.