title: A genetic screen for modifiers of a kinase suppressor of Ras-dependent rough eye phenotype in Drosophila.
abstract: kinase suppressor of Ras (ksr) encodes a putative protein kinase that by genetic criteria appears to function downstream of RAS in multiple receptor tyrosine kinase (RTK) pathways. While biochemical evidence suggests that the role of KSR is closely linked to the signal transduction mechanism of the MAPK cascade, the precise molecular function of KSR remains unresolved. To further elucidate the role of KSR and to identify proteins that may be required for KSR function, we conducted a dominant modifier screen in Drosophila based on a KSR-dependent phenotype. Overexpression of the KSR kinase domain in a subset of cells during Drosophila eye development blocks photoreceptor cell differentiation and results in the external roughening of the adult eye. Therefore, mutations in genes functioning with KSR might modify the KSR-dependent phenotype. We screened approximately 185,000 mutagenized progeny for dominant modifiers of the KSR-dependent rough eye phenotype. A total of 15 complementation groups of Enhancers and four complementation groups of Suppressors were derived. Ten of these complementation groups correspond to mutations in known components of the Ras1 pathway, demonstrating the ability of the screen to specifically identify loci critical for Ras1 signaling and further confirming a role for KSR in Ras1 signaling. In addition, we have 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 Ras1 pathway in general is discussed.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
authors.forename: M
authors.initials: M
authors.lastname: Therrien
authors.forename: D K
authors.initials: DK
authors.lastname: Morrison
authors.forename: A M
authors.initials: AM
authors.lastname: Wong
authors.forename: G M
authors.initials: GM
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000201:enzymology / Q000235:genetics*; D005020:Ethyl Methanesulfonate; D005123:Eye / Q000033:anatomy & histology / Q000648:ultrastructure; D005260:Female; D005799:Genes, Dominant; D017344:Genes, Insect; D005816:Genetic Complementation Test; D008297:Male; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005020:Ethyl Methanesulfonate; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D020794:Receptor Protein-Tyrosine Kinases