The Caenorhabditis elegans homologue of the proto-oncogene ect-2 positively regulates RAS signalling during vulval development |
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Authors: | Canevascini Stefano Marti Mark Fröhli Erika Hajnal Alex |
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Institution: | Institute of Zoology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. |
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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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