The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction.
Vulval induction in C. elegans is controlled by a highly conserved signaling pathway similar to the RTK-Ras-MAPK cascade in mammals. By screening for suppressors of the Multivulva phenotype caused by an activated let-60 ras allele, we isolated mutations in a gene, ksr-1, that acts as a positive modifier of vulval induction and is required for at least two other let-60 ras-mediated processes. Although ksr-1 mutations do not perturb vulval induction in an otherwise wild-type background, they have very strong effects on vulval induction in genetic backgrounds where Ras pathway activity is constitutively activated or compromised, suggesting that ksr-1 activity is required for maximal stimulation of vulval fates by the Ras pathway. Genetic epistasis analysis suggests that ksr-1 acts downstream of or in parallel to let-60 ras. We cloned ksr-1 and have shown that it encodes a novel putative protein kinase related to the Raf family of Ser/Thr kinases.
Department of Molecular, University of Colorado, Boulder 80309-0347, USA.
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Sundaram
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Han
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004627:Embryonic Induction; D004843:Epistasis, Genetic; D005260:Female; D018628:Gene Dosage; D017238:Genes, Helminth / Q000235:genetics*; D016153:Genes, Suppressor / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D014844:Vulva / Q000196:embryology; D018631:ras Proteins / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins