The Caenorhabditis elegans homologue of the proto-oncogene ect-2 positively regulates RAS signalling during vulval development.
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.
Canevascini
Stefano
S
Institute of Zoology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Marti
Mark
M
Fröhli
Erika
E
Hajnal
Alex
A
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004627:Embryonic Induction / Q000502:physiology; D004843:Epistasis, Genetic; D005260:Female; D017238:Genes, Helminth; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011519:Proto-Oncogenes / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014844:Vulva / Q000196:embryology* / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C507872:Ect-2 protein, C elegans; D020662:Guanine Nucleotide Exchange Factors; D018631:ras Proteins