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Tissue-specific functions of the Caenorhabditis elegans p120 Ras GTPase activating protein GAP-3


Stetak, A; Gutierrez, P; Hajnal, A (2008). Tissue-specific functions of the Caenorhabditis elegans p120 Ras GTPase activating protein GAP-3. Developmental Biology, 323(2):166-176.

Abstract

All metazoan genomes encode multiple RAS GTPase activating proteins (RasGAPs) that negatively regulate the conserved RAS/MAPK signaling pathway. In mammals, several RasGAPs exhibit tumor suppressor activity by preventing excess RAS signal transduction. We have identified gap-3 as the to date missing Caenorhabditiselegans member of the p120 RasGAP family. By studying the genetic interaction of gap-3 with the two previously identified RasGAPs gap-1 and gap-2, we find that different combinations of RasGAPs are used to repress LET-60 RAS signaling depending on the cellular context. GAP-3 is the predominant negative regulator of RAS during meiotic progression of the germ cells, while GAP-1 is the key inhibitor of RAS during vulval induction. In other tissues such as the sex myoblasts or the chemosensory neurons, all three RasGAPs act in concert. The C. elegans RasGAPs have thus undergone partial specialization after gene duplication to allow the differential regulation of the RAS/MAPK signaling pathway in different cell types. A similar tissue specialization of the human tumor suppressor genes may explain the strong bias in the type of cancer they promote when mutated.

All metazoan genomes encode multiple RAS GTPase activating proteins (RasGAPs) that negatively regulate the conserved RAS/MAPK signaling pathway. In mammals, several RasGAPs exhibit tumor suppressor activity by preventing excess RAS signal transduction. We have identified gap-3 as the to date missing Caenorhabditiselegans member of the p120 RasGAP family. By studying the genetic interaction of gap-3 with the two previously identified RasGAPs gap-1 and gap-2, we find that different combinations of RasGAPs are used to repress LET-60 RAS signaling depending on the cellular context. GAP-3 is the predominant negative regulator of RAS during meiotic progression of the germ cells, while GAP-1 is the key inhibitor of RAS during vulval induction. In other tissues such as the sex myoblasts or the chemosensory neurons, all three RasGAPs act in concert. The C. elegans RasGAPs have thus undergone partial specialization after gene duplication to allow the differential regulation of the RAS/MAPK signaling pathway in different cell types. A similar tissue specialization of the human tumor suppressor genes may explain the strong bias in the type of cancer they promote when mutated.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Ras; GTPase; GAP; Tumor; Suppressor
Language:English
Date:15 November 2008
Deposited On:23 Jan 2009 15:33
Last Modified:05 Apr 2016 12:47
Publisher:Elsevier
ISSN:0012-1606
Publisher DOI:10.1016/j.ydbio.2008.08.026
PubMed ID:18805410
Permanent URL: http://doi.org/10.5167/uzh-9430

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