The C. Elegans ksr-1 Gene Encodes a Novel Raf-related Kinase Involved in Ras-mediated Signal Transduction

Cell. 1995 Dec 15;83(6):889-901. doi: 10.1016/0092-8674(95)90205-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics*
  • Chromosome Mapping
  • Cloning, Molecular
  • Embryonic Induction
  • Epistasis, Genetic
  • Female
  • Gene Dosage
  • Genes, Helminth / genetics*
  • Genes, Suppressor / genetics
  • Molecular Sequence Data
  • Mutation
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-raf
  • Sequence Analysis, DNA
  • Signal Transduction / physiology*
  • Vulva / embryology
  • ras Proteins / physiology*

Substances

  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • ras Proteins

Associated data

  • GENBANK/U38820