Conservation of an inhibitor of the epidermal growth factor receptor, Kekkon1, in dipterans

被引:10
作者
Derheimer, FA [1 ]
MacLaren, CM [1 ]
Weasner, BP [1 ]
Alvarado, D [1 ]
Duffy, JB [1 ]
机构
[1] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
关键词
D O I
10.1534/genetics.166.1.213
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Regulation of epidermal growth factor receptor (EGFR) signaling requires the concerted action of both positive and negative factors. While the existence of numerous molecules that stimulate EGFK activity has been well documented, direct biological inhibitors appear to be more limited in number and phylogenetic distribution. Kekkonl (Kekl) represents one such inhibitor. Kekl was initially identified in Drosophila melanogaster and appears to be absent from vertebrates and the invertebrate Caenorhabditis. To further investigate Kekl's function and evolution, we identified kekl orthologs within dipterans. In D. melanogaster kekl is a transcriptional target of EGFR signaling during oogenesis, where it acts to attenuate receptor activity through an inhibitory feedback loop. The extracellular and transmembrane portion of Kekl is sufficient for its inhibitory activity in D. melanogaster. Consistent with conservation of its role in EGFR signaling, interspecies comparisons indicate a high degree of identity throughout these regions. During formation of the dorsal-ventral axis Kekl is expressed in dorsal follicle cells in a pattern that reflects the profile of receptor activation. D. virilis Kekl (DvKekl) is also expressed dynamically in the dorsal follicle cells, supporting a conserved role in EGFR signaling. Confirming this, biochemical and transgenic assays indicate that DvKekl is functionally interchangeable with DmKekl. Strikingly, we find that the cytoplasmic domain contains a region with the highest degree of conservation, which we have implicated in EGFR inhibition and dubbed the Kek tail (KT) box.
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页码:213 / 224
页数:12
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