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EMBO reports 6, 12, 1169–1175 (2005)
doi:10.1038/sj.embor.7400574
Published online: 4 November 2005
The Caenorhabditis elegans homologue of the proto-oncogene ect-2 positively regulates RAS signalling during vulval development
Stefano Canevascini†*, Mark Marti*, Erika Fröhli & Alex Hajnal
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Institute of Zoology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
To whom correspondence should be addressed
Alex Hajnal Tel: +41 44 6354854; Fax: +41 44 6356878; E-mail: ahajnal@zool.unizh.ch
† Present address: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
* These authors contributed equally to this work
Received 27 May 2005; Accepted 10 October 2005; Published online 4 November 2005.
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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.
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