IfkA, a presumptive eIF2 alpha kinase of Dictyostelium, is required for proper timing of aggregation and regulation of mound size.
IfkA, a presumptive eIF2 alpha kinase of Dictyostelium, is required for proper timing of aggregation and regulation of mound size.
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DOI：
10.1186/1471-213x-3-3
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发表时间：
2003-04-09
影响因子：
--
通讯作者：
Singleton CK
中科院分区：
文献类型：
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作者：
Fang R;Xiong Y;Singleton CK
竹鞭毛虫从生长到发育的转变是由生长中的异形虫的氨基酸饥饿所启动的。在其他真核生物中，氨基酸饥饿的一个关键传感器和由此产生的生理反应的中介是GCN2蛋白，它是一种eIF2α激酶。GCN2通过磷酸化翻译起始因子eIF2α，下调BUCK基因翻译的起始，增强特定mRNAs的翻译。在网柄网柄菌中发现了两个eif2α激酶，并在此进行了研究。这两个eif2α激酶似乎都不参与感知氨基酸饥饿以启动发育。然而，其中一种激酶IfkA在发育开始后1-7小时内对eIF2mRNA进行磷酸化，导致大量α从多聚体转变为游离核糖体。在缺乏eif2α磷酸化的情况下，ifkA缺失细胞比正常细胞更早聚集，形成土丘，最终形成比正常大的子实体。IfkA缺失细胞的早期聚集表型反映了明显的、比正常更早的cAMP脉冲系统的建立。大土丘的表型是由于细胞外Countin水平降低所致，Countin是调节土丘大小的计数因子的一个组成部分。在野生型细胞中，IfkA对eIF2mRNA的磷酸化导致了Countinα的特异性稳定和翻译效率的提高，尽管翻译减少会导致整体mRNA的翻译减少。IfkA是网柄苔藓中的一种eIF2α激酶，通常在发育开始后的1-7小时内或在聚集前阶段磷酸化eIF2α。这导致在这段时间内蛋白质合成的启动总体减少，与大多数mRNAs相关的核糖体数量也随之减少。然而，对于一些α，在eIF2 mRNA磷酸化增加的条件下，蛋白质合成的启动被增强或稳定。这包括Countin mRNA。
The transition from growth to development in Dictyostelium is initiated by amino acid starvation of growing amobae. In other eukaryotes, a key sensor of amino acid starvation and mediator of the resulting physiological responses is the GCN2 protein, an eIF2α kinase. GCN2 downregulates the initiation of translation of bulk mRNA and enhances translation of specific mRNAs by phosphorylating the translation initiation factor eIF2α. Two eIF2α kinases were identified in Dictyostelium and studied herein. Neither of the eIF2α kinases appeared to be involved in sensing amino acid starvation to initiate development. However, one of the kinases, IfkA, was shown to phosphorylate eIF2α from 1 to 7 hours after the onset of development, resulting in a shift from polysomes to free ribosomes for bulk mRNA. In the absence of the eIF2α phosphorylation, ifkA null cells aggregated earlier than normal and formed mounds and ultimately fruiting bodies that were larger than normal. The early aggregation phenotype in ifkA null cells reflected an apparent, earlier than normal establishment of the cAMP pulsing system. The large mound phenotype resulted from a reduced extracellular level of Countin, a component of the counting factor that regulates mound size. In wild type cells, phosphorylation of eIF2α by IfkA resulted in a specific stabilization and enhanced translational efficiency of countin mRNA even though reduced translation resulted for bulk mRNA. IfkA is an eIF2α kinase of Dictyostelium that normally phosphorylates eIF2α from 1 to 7 hours after the onset of development, or during the preaggregation phase. This results in an overall reduction in the initiation of protein synthesis during this time frame and a concomitant reduction in the number of ribosomes associated with most mRNAs. For some mRNAs, however, initiation of protein synthesis is enhanced or stabilized under the conditions of increased eIF2α phosphorylation. This includes countin mRNA.