AN AMINO-ACID SUBSTITUTION IN THE DROSOPHILA HOP(TUM-L) JAK KINASE CAUSES LEUKEMIA-LIKE HEMATOPOIETIC DEFECTS
AN AMINO-ACID SUBSTITUTION IN THE DROSOPHILA HOP(TUM-L) JAK KINASE CAUSES LEUKEMIA-LIKE HEMATOPOIETIC DEFECTS
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DOI：
10.1002/j.1460-2075.1995.tb07127.x
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发表时间：
1995-04-03
期刊：
影响因子：
11.4
通讯作者：
DEAROLF, CR
中科院分区：
文献类型：
--
作者：
LUO, H;HANRATTY, WP;DEAROLF, CR
非受体激酶Jak家族的蛋白质在哺乳动物造血信号转导中起重要作用。它们介导细胞对多种细胞因子和生长因子的应答。果蝇Jak激酶中的显性突变，跳房子（肿瘤致死）（hop（Tum-1）），导致造血缺陷。在这里，我们进行啤酒花（Tum-1）的分子分析。我们证明，啤酒花（Tum-1）造血表型是由一个单一的氨基酸取代甘氨酸谷氨酸残基341。我们产生了啤酒花（Tum-1）突变的真正回复突变体，其中分子损伤和突变的造血表型都恢复到野生型。我们还研究了G341 E取代在转基因果蝇中的作用。结果表明，突变的Jak激酶可导致白血病样异常。
Proteins of the Jak family of non-receptor kinases play important roles in mammalian hematopoietic signal transduction. They mediate the cellular response to a wide range of cytokines and growth factors. A dominant mutation in a Drosophila Jak kinase, hopscotch(Tumorous-lethal) (hop(Tum-l)), causes hematopoietic defects. Here we conduct a molecular analysis of hop(Tum-l). We demonstrate that the hop(Tum-l) hematopoietic phenotype is caused by a single amino acid substitution of glycine to glutamic acid at residue 341. We generate a true revertant of the hop(Tum-l) mutation, in which both the molecular lesion and the mutant hematopoietic phenotype revert back to wild type. We also examine the effects of the G341E substitution in transgenic flies. The results indicate that a mutant Jak kinase can cause leukemia-like abnormalities.