A genetic screen for modifiers of Drosophila Src42A identifies mutations in Egfr, rolled and a novel signaling gene

Drosophila Src42A, a close relative of the vertebrate c-Src, has been impli cated in the Ras-Mapk signaling cascade. An allele of Src42A, Su(Raf)1, dom inantly suppresses the lethality of partial loss-of-function Raf mutations. To isolate genes involved in the same pathway where Src42A functions, we c arried 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 Dros ophila EGF Receptor (Egfr), rolled Src42A, and two other new loci, one of w hich was named semang (sag). During embryogenesis, sag affects the developm ent of the head, tail, and tracheal branches, suggesting that it participat es in the pathways of Torso and DFGF-R1 receptor tyrosine kinases. sag also disrupts the embryonic peripheral nervous system. During the development o f 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-fu nction Raf and rl, but suppresses those of activated Ras1(V12) mutation. Th is work provides the first genetic evidence that both Src42A and sag are mo dulators of RTK signaling.