Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics*
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Caenorhabditis elegans Proteins / metabolism
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Embryo, Nonmammalian
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Embryonic Induction / physiology
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Epistasis, Genetic
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Female
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Genes, Helminth
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Guanine Nucleotide Exchange Factors / chemistry
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism*
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Models, Biological
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Molecular Sequence Data
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Protein Structure, Tertiary
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Proto-Oncogenes / genetics*
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Sequence Deletion
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Sequence Homology, Amino Acid
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Signal Transduction*
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Vulva / embryology*
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Vulva / metabolism
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ras Proteins / metabolism*
Substances
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Caenorhabditis elegans Proteins
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Ect-2 protein, C elegans
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Guanine Nucleotide Exchange Factors
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ras Proteins