The Caenorhabditis elegans homologue of the proto-oncogene ect-2 positively regulates RAS signalling during vulval development

EMBO Rep. 2005 Dec;6(12):1169-75. doi: 10.1038/sj.embor.7400574.


Guanine nucleotide exchange factors (GEFs) regulate the activity of small GTP-binding proteins in a variety of biological processes. We have identified a gain-of-function mutation in the Caenorhabditis elegans GEF ect-2, the homologue of the mammalian ect2 proto-oncogene that has an essential role during cytokinesis. Here, we report that, in addition to its known function during mitosis, ECT-2 promotes the specification of the primary vulval cell fate by activating RAS/mitogen-activated protein kinase (MAPK) signalling before the end of the S-phase. Epistasis analysis indicates that ECT-2 crosstalks to the canonical RAS/MAPK cascade upstream of the RAS GEF SOS-1 by means of a RHO-1 signalling pathway. Our results raise the possibility that the transforming activity of the mammalian ect-2 oncogene could be due to hyperactivation of the RAS/MAPK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Embryo, Nonmammalian
  • Embryonic Induction / physiology
  • Epistasis, Genetic
  • Female
  • Genes, Helminth
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proto-Oncogenes / genetics*
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Vulva / embryology*
  • Vulva / metabolism
  • ras Proteins / metabolism*


  • Caenorhabditis elegans Proteins
  • Ect-2 protein, C elegans
  • Guanine Nucleotide Exchange Factors
  • ras Proteins