HUMAN P68 KINASE EXHIBITS GROWTH SUPPRESSION IN YEAST AND HOMOLOGY TO THE TRANSLATIONAL REGULATOR GCN2
HUMAN P68 KINASE EXHIBITS GROWTH SUPPRESSION IN YEAST AND HOMOLOGY TO THE TRANSLATIONAL REGULATOR GCN2
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DOI：
10.1002/j.1460-2075.1992.tb05200.x
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发表时间：
1992-04-01
期刊：
影响因子：
11.4
通讯作者：
WILLIAMS, BRG
中科院分区：
文献类型：
--
作者：
CHONG, KL;FENG, L;WILLIAMS, BRG
人 p68 激酶是一种干扰素调节酶，被双链 RNA 激活时会抑制蛋白质合成。我们在此表明，当在酿酒酵母中表达时，p68 激酶产生生长抑制表型，这是由于与功能性蛋白激酶活性一致的多肽链起始抑制所致。这种缓慢生长的表型在酵母中通过两种不同的机制得以恢复：p68激酶N末端的表达（显示出在体外结合双链RNA）和酵母起始因子2的α亚基的突变形式的表达（在单个可磷酸化位点发生改变）。这些结果提供了第一个直接的体内证据，证明 p68 激酶与真核起始因子 2 的 α 亚基相互作用。与酵母翻译调节因子 GCN2 的序列相似性进一步表明，该酶可能是高等真核生物中的功能同源物，其正常功能是通过起始因子 2 磷酸化来调节蛋白质合成。
The human p68 kinase is an interferon-regulated enzyme that inhibits protein synthesis when activated by double-stranded RNA. We show here that when expressed in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing phenotype resulting from an inhibition of polypeptide chain initiation consistent with functional protein kinase activity. This slow growth phenotype was reverted in yeast by two different mechanisms: expression of the p68 kinase N-terminus, shown to bind double-stranded RNA in vitro and expression of a mutant form of the alpha-subunit of yeast initiation factor 2, altered at a single phosphorylatable site. These results provide the first direct in vivo evidence that the p68 kinase interacts with the alpha-subunit of eukaryotic initiation factor 2. Sequence similarity with a yeast translational regulator, GCN2, further suggests that this enzyme may be a functional homolog in higher eukaryotes, where its normal function is to regulate protein synthesis through initiation factor 2 phosphorylation.