title: A misexpression screen identifies genes that can modulate RAS1 pathway signaling in Drosophila melanogaster.
abstract: Differentiation of the R7 photoreceptor cell is dependent on the Sevenless receptor tyrosine kinase, which activates the RAS1/mitogen-activated protein kinase signaling cascade. Kinase suppressor of Ras (KSR) functions genetically downstream of RAS1 in this signal transduction cascade. Expression of dominant-negative KSR (KDN) in the developing eye blocks RAS pathway signaling, prevents R7 cell differentiation, and causes a rough eye phenotype. To identify genes that modulate RAS signaling, we screened for genes that alter RAS1/KSR signaling efficiency when misexpressed. In this screen, we recovered three known genes, Lk6, misshapen, and Akap200. We also identified seven previously undescribed genes; one encodes a novel rel domain member of the NFAT family, and six encode novel proteins. These genes may represent new components of the RAS pathway or components of other signaling pathways that can modulate signaling by RAS. We discuss the utility of gain-of-function screens in identifying new components of signaling pathways in Drosophila.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Huang
authors.forename: G M
authors.initials: GM
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017344:Genes, Insect; D005838:Genotype; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*; D018631:ras Proteins
chemical_list: D029721:Drosophila Proteins; D019476:Insect Proteins; D011494:Protein Kinases; C097199:KSR-1 protein kinase; C113875:msn protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C417283:Ras85D protein, Drosophila; D018631:ras Proteins