A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress
A novel role for protein kinase Gcn2 in yeast tolerance to intracellular acid stress
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DOI：
10.1042/bj20111264
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发表时间：
2012-01-01
影响因子：
4.1
通讯作者：
Serrano, Ramon
中科院分区：
文献类型：
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作者：
Hueso, Guillem;Aparicio-Sanchis, Rafael;Serrano, Ramon
细胞内pH调节许多细胞系统，但其调节和感知机制大多未知。我们已经确定了两个重要的酵母基因耐受细胞内酸化所造成的弱渗透性酸。一个对应于LEU 2，并且通过去除leu 2突变宿主菌株对细胞外亮氨酸摄取的依赖性来起作用。亮氨酸转运受到细胞内酸化的抑制，并且亮氨酸过量补充或转运蛋白基因BAP 2的过表达改善了酸的生长。另一个耐酸基因是GCN 2，编码一种蛋白激酶，在氨基酸饥饿期间被不带电荷的tRNA激活。Gcn 2磷酸化eIF 2 α（真核起始因子2 α）（Sui 2）的Ser（51），这抑制了一般的翻译，但激活了Gcn 4，一种氨基酸生物合成基因的转录因子。细胞内酸化可能通过抑制氨酰-tRNA合成酶来激活Gcn 2，因为我们观察到不带电荷的tRNA（Leu）的积累而没有亮氨酸耗尽。gcn 2是亮氨酸转运所必需的，如果是亮氨酸营养缺陷型，gcn 2缺失突变体对酸胁迫敏感。Gcn 4既不是亮氨酸转运所必需的，也不是酸耐受性所必需的，但是S51 A sui 2突变体是酸敏感的。这表明，Gcn 2，通过磷酸化eIF 2 α，可以激活翻译的氨基酸转运蛋白的一个未知的调节剂不同的Gcn 4。
Intracellular pH conditions many cellular systems, but its mechanisms of regulation and perception are mostly unknown. We have identified two yeast genes important for tolerance to intracellular acidification caused by weak permeable acids. One corresponded to LEU2 and functions by removing the dependency of the leu2 mutant host strain on uptake of extracellular leucine. Leucine transport is inhibited by intracellular acidification, and either leucine oversupplementation or overexpression of the transporter gene BAP2 improved acid growth. Another acid-tolerance gene is GCN2, encoding a protein kinase activated by uncharged tRNAs during amino acid starvation. Gcn2 phosphorylates eIF2 alpha (eukaryotic initiation factor 2 alpha) (Sui2) at Ser(51) and this inhibits general translation, but activates that of Gcn4, a transcription factor for amino acid biosynthetic genes. Intracellular acidification activates Gcn2 probably by inhibition of aminoacyl-tRNA synthetases because we observed accumulation of uncharged tRNA(leu) without leucine depletion. Gcn2 is required for leucine transport and a gcn2-null mutant is sensitive to acid stress if auxotrophic for leucine. Gcn4 is required for neither leucine transport nor acid tolerance, but a S51A sui2 mutant is acid-sensitive. This suggests that Gcn2, by phosphorylating eIF2 alpha, may activate translation of an unknown regulator of amino acid transporters different from Gcn4.