A Genetic Screen for Modifiers of Drosophila Src42A Identifies Mutations in Egfr, rolled and a Novel Signaling Gene

摘要

Drosophila Src42A , a close relative of the vertebrate c-Src , has been implicated in the Ras-Mapk signaling cascade. An allele of Src42A, Su(Raf)1 , dominantly suppresses the lethality of partial loss-of-function Raf mutations. To isolate genes involved in the same pathway where Src42A functions, we carried out genetic screens for dominant suppressor mutations that prevented Su(Raf)1 from suppressing Raf. Thirty-six mutations representing at least five genetic loci were recovered from the second chromosome. These are Drosophila EGF Receptor (Egfr), rolled, Src42A , and two other new loci, one of which was named semang ( sag ). During embryogenesis, sag affects the development of the head, tail, and tracheal branches, suggesting that it participates in the pathways of Torso and DFGF-R1 receptor tyrosine kinases. sag also disrupts the embryonic peripheral nervous system. During the development of imaginal discs, sag affects two processes known to require Egfr signaling: the recruitment of photoreceptor cells and wing vein formation. Thus sag functions in several receptor tyrosine kinase (RTK)-mediated processes. In addition, sag dominantly enhances the phenotypes associated with loss-of-function Raf and rl , but suppresses those of activated Ras1V12 mutation. This work provides the first genetic evidence that both Src42A and sag are modulators of RTK signaling.