title: A lin-45 raf enhancer screen identifies eor-1, eor-2 and unusual alleles of Ras pathway genes in Caenorhabditis elegans.
abstract: In Caenorhabditis elegans, the Ras/Raf/MEK/ERK signal transduction pathway controls multiple processes including excretory system development, P12 fate specification, and vulval cell fate specification. To identify positive regulators of Ras signaling, we conducted a genetic screen for mutations that enhance the excretory system and egg-laying defects of hypomorphic lin-45 raf mutants. This screen identified unusual alleles of several known Ras pathway genes, including a mutation removing the second SH3 domain of the sem-5/Grb2 adaptor, a temperature-sensitive mutation in the helical hairpin of let-341/Sos, a gain-of-function mutation affecting a potential phosphorylation site of the lin-1 Ets domain transcription factor, a dominant-negative allele of ksr-1, and hypomorphic alleles of sur-6/PP2A-B, sur-2/Mediator, and lin-25. In addition, this screen identified multiple alleles of two newly identified genes, eor-1 and eor-2, that play a relatively weak role in vulval fate specification but positively regulate Ras signaling during excretory system development and P12 fate specification. The spectrum of identified mutations argues strongly for the specificity of the enhancer screen and for a close involvement of eor-1 and eor-2 in Ras signaling.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Christian E
authors.initials: CE
authors.lastname: Rocheleau
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Howard
authors.forename: Alissa P
authors.initials: AP
authors.lastname: Goldman
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Volk
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Girard
authors.forename: Meera V
authors.initials: MV
authors.lastname: Sundaram
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D017238:Genes, Helminth; D005809:Genes, Regulator; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015398:Signal Transduction; D048490:raf Kinases; D018631:ras Proteins / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; C463999:EOR-1 protein, C elegans; C464000:EOR-2 protein, C elegans; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; C454817:lin-45 protein, C elegans; D048490:raf Kinases; D018631:ras Proteins