Yan R, Small S, Desplan C, Dearolf C R, Darnell J E
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021, USA.
Cell. 1996 Feb 9;84(3):421-30. doi: 10.1016/s0092-8674(00)81287-8.
A Drosophila Stat gene (D-Stat) with a zygotic segmental expression pattern was identified. This protein becomes phosphorylated on Tyr-704 when coexpressed in Schneider cells with a Drosophila janus kinase (JAK), Hopscotch (HOP). The phosphorylated protein binds specifically to the consensus sequence TTCCCGGAA. Suppressor mutations of hopTum-I, a dominant hyperactive allele of hop whose phenotype is hematocyte overproduction and tumor formation, were selected. One of these mutants, statHJ, mapped to the same chromosomal region (92E) as does D-Stat, had an incompletely penetrant pair rule phenotype, and exhibited aberrant expression of the pair rule gene even skipped (eve) at the cellular blastoderm stage. Two D-STAT-binding sites were identified within the eve stripe 3 enhancer region. Mutations in either of the STAT-binding sites greatly decreased the stripe 3 expression in transgenic flies. Clearly, the JAK-STAT pathway is connected to Drosophila early development.
鉴定出一种具有合子节段表达模式的果蝇Stat基因(D-Stat)。当该蛋白在施奈德细胞中与果蝇janus激酶(JAK)霍普斯科奇(HOP)共表达时,其酪氨酸704位点会发生磷酸化。磷酸化的蛋白特异性结合共有序列TTCCCGGAA。筛选了hopTum-I(hop的一个显性高活性等位基因,其表型为血细胞过度增殖和肿瘤形成)的抑制突变。其中一个突变体statHJ定位于与D-Stat相同的染色体区域(92E),具有不完全显性的体节极性表型,并且在细胞胚盘阶段表现出体节极性基因even skipped(eve)的异常表达。在eve条纹3增强子区域内鉴定出两个D-STAT结合位点。两个STAT结合位点中的任何一个发生突变都会大大降低转基因果蝇中条纹3的表达。显然,JAK-STAT信号通路与果蝇早期发育相关。