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

被引:12
作者
Stetak, Attila [1 ]
Gutierrez, Peter [1 ]
Hajnal, Alex [1 ]
机构
[1] Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
Ras; GTPase; GAP; Tumor; Suppressor;
D O I
10.1016/j.ydbio.2008.08.026
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 Caenorhabditis elegans member of the p 120 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. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:166 / 176
页数:11
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