SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc
SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc
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DOI：
10.1038/sj.onc.1205618
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发表时间：
2002-07-18
期刊：
影响因子：
8
通讯作者：
Mathey-Prevot, B
中科院分区：
文献类型：
--
作者：
Callus, BA;Mathey-Prevot, B
我们从果蝇中克隆了一个新的SOCS基因socs 36 E，它与哺乳动物的SOCS-5基因同源性最高。Socs 36 E主要在胚胎发生期间以高度动态的模式合子表达。SOCS 36 E在转基因果蝇中的体内表达导致几种成体表型。GAL 4定向表达导致翅前横静脉缺失、肱骨外生长、缺乏笼头和眼睛色素沉着缺陷。在无翅GAL 4控制下的SOCS 36 E表达导致伸展的翅膀。这些表型的完全突变需要SOCS 36 E的SH 2和SOCS-box结构域的存在。所观察到的表型与JAK/STAT或EGF-R信号传导缺陷一致，并且加剧了d-stat（stat 92 E）或d-egf-r（der）基因杂合的jak（跳房子）、din果蝇。相反，失活一个拷贝的d-cbl基因，一个负调节因子的d-EGF-R，部分挽救了翅膀表型。这些遗传相互作用意味着SOCS 36 E可以抑制翼盘中JAK/STAT和EGF-R信号通路的活性，并表明SOCS 36 E在体内与多种通路相互作用。
We have cloned a novel SOCS gene from Drosophila, socs36E, which is most homologous to the mammalian socs-5 gene. Socs36E is expressed zygotically, predominantly during embryogenesis, in a highly dynamic pattern. In vivo expression of SOCS36E in transgenic flies results in several adult phenotypes. Engrailed-GAL4 directed expression causes loss of the wing anterior cross vein, humeral outgrowths, absence of halteres and eye pigmentation defects. Expression of SOCS36E under apterous-GAL4 control resulted in outstretched wings. Full penetrance of these phenotypes required the presence of the SH2 and SOCS-box domains of SOCS36E. The observed phenotypes were consistent with defects in JAK/STAT or EGF-R signalling and were exacerbated jak (hopscotch), din flies heterozygous for either the d-stat (stat92E) or d-egf-r (der) genes. Conversely, inactivating one copy of the d-cbl gene, a negative regulator of the d-EGF-R, partially rescued the wing phenotypes. These genetic interactions imply that SOCS36E can suppress activities of the JAK/STAT and EGF-R signalling pathways in the wing disc and suggest that SOCS36E interacts with multiple pathways in vivo.