Bruinsma Janelle J, Jirakulaporn Tanawat, Muslin Anthony J, Kornfeld Kerry
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Dev Cell. 2002 May;2(5):567-78. doi: 10.1016/s1534-5807(02)00151-x.
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 Zn(2+) efflux and reducing the concentration of cytosolic Zn(2+), and cytosolic Zn(2+) negatively regulates Ras-mediated signaling. Physiological concentrations of Zn(2+) cause a significant inhibition of Ras-mediated signaling. These findings suggest that Zn(2+) negatively regulates a conserved element of the signaling pathway and that Zn(2+) regulation is important for maintaining the inactive state of the Ras pathway.
秀丽隐杆线虫的cdf-1是在一项针对Ras介导信号传导调节因子的遗传筛选中被鉴定出来的。CDF-1是一种阳离子扩散促进蛋白，在结构和功能上与脊椎动物的ZnT-1相似。这些蛋白质作为Ras途径的正向调节因子具有进化上保守的功能，并且Ras途径具有进化上保守的对CDF蛋白作出反应的能力。CDF蛋白通过促进Zn(2+)外流并降低胞质Zn(2+)浓度来调节Ras介导的信号传导，而胞质Zn(2+)对Ras介导的信号传导起负调节作用。生理浓度的Zn(2+)会显著抑制Ras介导的信号传导。这些发现表明，Zn(2+)对信号通路的一个保守元件起负调节作用，并且Zn(2+)调节对于维持Ras途径的非活性状态很重要。
