A genetic screen for modifiers of a kinase suppressor of ras-dependent rough eye phenotype in drosophila

kinase suppressor of Ras (ksr) encodes a putative protein kinase that by ge netic criteria appears to function downstream of RAS in multiple receptor t yrosine kinase (RTK) pathways. While biochemical evidence suggests that the role of KSR is closely linked to the signal transduction mechanism of die MAPK cascade, the precise molecular function of KSR remains unresolved. To further elucidate the role of KSR and to identify proteins that may be requ ired for KSR function, we conducted a dominant modifier screen in Drosophil a based on a KSR-dependent phenotype. Overexpression of the KSR kinase doma in in a subset of cells during Drosophila eye development blocks photorecep tor cell differentiation and results in the external roughening of the adul t eye. Therefore, mutations in genes functioning with KSR might modify the KSR-dependent phenotype. We screened similar to 185,000 mutagenized progeny for dominant modifiers of the KSR-dependent rough eye phenotype. A total o f 15 complementation groups of Enhancers and four complementation groups of Suppressors were derived. Ten of these complementation groups correspond t o mutations in known components of the Ras1 pathway, demonstrating the abil ity of the screen to specifically identify loci critical for Ras1 signaling and further confirming a role for KSR in Ras1 signaling. In addition, we h ave identified 4 additional complementation groups. One of them corresponds to the kismet locus, which encodes a putative chromatin remodeling factor. The relevance of these loci with respect to the function of KSR and the: R as1 pathway in general is discussed.