ENABLED, A DOSAGE-SENSITIVE SUPPRESSOR OF MUTATIONS IN THE DROSOPHILA ABL TYROSINE KINASE, ENCODES AN ABL SUBSTRATE WITH SH3 DOMAIN-BINDING PROPERTIES
ENABLED, A DOSAGE-SENSITIVE SUPPRESSOR OF MUTATIONS IN THE DROSOPHILA ABL TYROSINE KINASE, ENCODES AN ABL SUBSTRATE WITH SH3 DOMAIN-BINDING PROPERTIES
复制标题
DOI：
10.1101/gad.9.5.521
复制
发表时间：
1995-03-01
影响因子：
10.5
通讯作者：
HOFFMANN, FM
中科院分区：
文献类型：
--
作者：
GERTLER, FB;COMER, AR;HOFFMANN, FM
在果蝇中，对抑制Abl突变致死性的显性第二位点突变进行遗传筛选，只确定了一个基因的等位基因，使能（ena）。我们报告，ena蛋白含有脯氨酸丰富的图案，并结合到Abl和Src SH 3结构域，ena也是Abl激酶的底物;当它在细胞中与人或果蝇Abl共表达时，ena的酪氨酸磷酸化增加，内源性ena酪氨酸磷酸化在Abl突变动物中减少。与Abl一样，ena在胚胎神经系统的轴突中表达水平最高，并且ena突变胚胎在轴突结构上存在缺陷。我们的结论是，果蝇Abl的一个关键功能是磷酸化和负调控ena蛋白在神经发育过程中。
Genetic screens for dominant second-site mutations that suppress the lethality of Abl mutations in Drosophila identified alleles of only one gene, enabled (ena). We report that the ena protein contains proline-rich motifs and binds to Abl and Src SH3 domains, ena is also a substrate for the Abl kinase; tyrosine phosphorylation of ena is increased when it is coexpressed in cells with human or Drosophila Abl and endogenous ena tyrosine phosphorylation is reduced in Abl mutant animals. Like Abl, ena is expressed at highest levels in the axons of the embryonic nervous system and ena mutant embryos have defects in axonal architecture. We conclude that a critical function of Drosophila Abl is to phosphorylate and negatively regulate ena protein during neural development.