title: A screen for mutations that prevent lethality caused by expression of activated sevenless and Ras1 in the Drosophila embryo.
abstract: Ras1 plays a critical role in receptor tyrosine kinase (RTK) signal transduction pathways that function during Drosophila development. We demonstrate that mis-expression of constitutively active forms of Ras1 (Ras1V12) and the Sevenless (Sev) RTK (SevS11) during embryogenesis causes lethality due to inappropriate activation of RTK/Ras1 signaling pathways. Genetic and molecular data indicate that the rate of SevS11/sev-Ras1V12 lethality is sensitive to the expression level of both transgenes. To identify genes that encode components of RTK/Ras1 signaling pathways or modulators of RNA polymerase II transcription, we took advantage of the dose-sensitivity of the system and screened for second site mutations that would dominantly suppress the lethality. The collection of identified suppressors includes the PR55 subunit of Protein Phosphatase 2A indicating that downstream of Sev and Ras1 this subunit acts as a negative regulator of phosphatase activity. The isolation of mutations in the histone deacetylase RPD3 suggests that it functions as positive regulator of sev enhancer-driven transcription. Finally, the isolation of mutations in the Trithorax group gene devenir and the characterized allelism with the Breathless RTK encoding gene provides evidence for Ras1-mediated regulation of homeotic genes.
authors.affiliation: Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: A
authors.initials: A
authors.lastname: Maixner
authors.forename: T P
authors.initials: TP
authors.lastname: Hecker
authors.forename: Q N
authors.initials: QN
authors.lastname: Phan
authors.forename: D A
authors.initials: DA
authors.lastname: Wassarman
mesh_terms: D000818:Animals; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases; D018631:ras Proteins / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D020794:Receptor Protein-Tyrosine Kinases; C056737:sev protein, Drosophila; D018631:ras Proteins