Cation diffusion facilitator proteins modulate Raf-1activity
Cation diffusion facilitator proteins modulate Raf-1activity
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DOI：
10.1074/jbc.m401210200
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发表时间：
2004-06-25
影响因子：
4.8
通讯作者：
Muslin, AJ
中科院分区：
文献类型：
--
作者：
Jirakulaporn, T;Muslin, AJ
RAS-细胞外信号调节激酶(ERK)级联通路是调控细胞生长、存活和分化的重要信号通路。以前的工作证实，RAS-GTP与蛋白激酶Raf-1结合并促进其激活。最近，通过秀丽隐杆线虫的遗传筛查发现，阳离子扩散促进因子(CDF)蛋白参与了RAS-ERK信号转导。在目前的工作中，我们证明了CDF蛋白可能在非洲爪哇卵母细胞中的RAS下游发挥作用，但在Raf-1的上游发挥作用。我们还发现线虫蛋白CDF-1及其哺乳动物同源物ZNT-1与Raf-1的氨基末端调节部分结合，并促进Raf-1的生物学和酶活性。此外，我们还发现锌离子抑制了Raf-1与ZNT-1的结合。我们提出了一个CDF蛋白结合促进Raf-1激活的模型。
The Ras-extracellular signal-regulated kinase (ERK) cascade is a critical intracellular signaling pathway that regulates growth, survival, and differentiation. Previous work established that Ras-GTP binds to, and facilitates the activation of, the protein kinase Raf-1. Recently, it was demonstrated that the cation diffusion facilitator (CDF) proteins are involved in Ras-ERK signaling by use of a Caenorhabditis elegans genetic screen that identified suppressors of activated Ras. In the current work, we demonstrate that CDF proteins may function downstream of Ras, but upstream of Raf-1 in Xenopus oocytes. We also show that the C. elegans protein CDF-1 and its mammalian homologue ZnT-1 bind to the amino-terminal regulatory portion of Raf-1 and promote the biological and enzymatic activity of Raf-1. Furthermore, we show that Zn2+ inhibits Raf-1 binding to ZnT-1. We propose a model in which CDF protein binding facilitates Raf-1 activation.