Olsen D S, Jordan B, Chen D, Wek R C, Cavener D R
Department of Molecular Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Genetics. 1998 Jul;149(3):1495-509. doi: 10.1093/genetics/149.3.1495.
Genomic and cDNA clones homologous to the yeast GCN2 eIF-2alpha kinase (yGCN2) were isolated from Drosophila melanogaster. The identity of the Drosophila GCN2 (dGCN2) gene is supported by the unique combination of sequence encoding a protein kinase catalytic domain and a domain homologous to histidyl-tRNA synthetase and by the ability of dGCN2 to complement a deletion mutant of the yeast GCN2 gene. Complementation of Deltagcn2 in yeast by dGCN2 depends on the presence of the critical regulatory phosphorylation site (serine 51) of eIF-2alpha. dGCN2 is composed of 10 exons encoding a protein of 1589 amino acids. dGCN2 mRNA is expressed throughout Drosophila development and is particularly abundant at the earliest stages of embryogenesis. The dGCN2 gene was cytogenetically and physically mapped to the right arm of the third chromosome at 100C3 in STS Dm2514. The discovery of GCN2 in higher eukaryotes is somewhat unexpected given the marked differences between the amino acid biosynthetic pathways of yeast vs. Drosophila and other higher eukaryotes. Despite these differences, the presence of GCN2 in Drosophila suggests at least partial conservation from yeast to multicellular organisms of the mechanisms responding to amino acid deprivation.
从黑腹果蝇中分离出了与酵母GCN2 eIF-2α激酶（yGCN2）同源的基因组和cDNA克隆。果蝇GCN2（dGCN2）基因的身份得到了编码蛋白激酶催化结构域和与组氨酰-tRNA合成酶同源结构域的序列独特组合的支持，以及dGCN2对酵母GCN2基因缺失突变体进行互补的能力的支持。dGCN2在酵母中对Δgcn2的互补作用取决于eIF-2α关键调节磷酸化位点（丝氨酸51）的存在。dGCN2由10个外显子组成，编码一个含有1589个氨基酸的蛋白质。dGCN2 mRNA在果蝇整个发育过程中均有表达，在胚胎发生的最早阶段尤其丰富。dGCN2基因通过细胞遗传学和物理定位，定位于第三条染色体右臂100C3处的STS Dm2514。鉴于酵母与果蝇及其他高等真核生物的氨基酸生物合成途径存在显著差异，在高等真核生物中发现GCN2有点出人意料。尽管存在这些差异，但果蝇中GCN2的存在表明，从酵母到多细胞生物，对氨基酸剥夺作出反应的机制至少有部分保守性。
