Drosophila gain-of-function mutant RTK torso triggers ectopic Dpp and STAT signaling.
Drosophila gain-of-function mutant RTK torso triggers ectopic Dpp and STAT signaling.
复制标题
果蝇功能获得突变体 RTK 躯干触发异位 Dpp 和 STAT 信号传导。
DOI：
10.1093/genetics/164.1.247
复制
发表时间：
2003
期刊：
影响因子：
3.3
通讯作者：
Li,WillisX
中科院分区：
文献类型：
--
作者：
Li,Jinghong;Li,WillisX
Overactivation of receptor tyrosine kinases (RTKs) has been linked to tumorigenesis. To understand how a hyperactivated RTK functions differently from wild-type RTK, we conducted a genome-wide systematic survey for genes that are required for signaling by a gain-of-function mutant Drosophila RTK Torso (Tor). We screened chromosomal deficiencies for suppression of a gain-of-function mutationtor(torGOF), which led to the identification of 26 genomic regions that, when in half dosage, suppressed the defects caused bytorGOF. Testing of candidate genes in these regions revealed many genes known to be involved in Tor signaling (such as those encoding the Ras-MAPK cassette, adaptor and structural molecules of RTK signaling, and downstream target genes of Tor), confirming the specificity of this genetic screen. Importantly, this screen also identified components of the TGFβ (Dpp) and JAK/STAT pathways as being required for TorGOFsignaling. Specifically, we found that reducing the dosage ofthickveins(tkv),Mothers against dpp(Mad), orSTAT92E(akamarelle), respectively, suppressedtorGOFphenotypes. Furthermore, we demonstrate that intorGOFembryos,dppis ectopically expressed and thus may contribute to the patterning defects. These results demonstrate an essential requirement of noncanonical signaling pathways for a persistently activated RTK to cause pathological defects in an organism.
