RRC ID 4302
著者 Stetak A, Gutierrez P, Hajnal A.
タイトル Tissue-specific functions of the Caenorhabditis elegans p120 Ras GTPase activating protein GAP-3.
ジャーナル Dev Biol
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.
巻・号 323(2)
ページ 166-76
公開日 2008-11-15
DOI 10.1016/j.ydbio.2008.08.026
PII S0012-1606(08)01160-3
PMID 18805410
MeSH Animals Body Patterning / drug effects Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology Caenorhabditis elegans / enzymology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Lineage / drug effects Chemotactic Factors / pharmacology Chemotaxis / drug effects Female GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism* Gene Expression Regulation, Developmental / drug effects Genes, Reporter Germ Cells / cytology Germ Cells / drug effects Myoblasts / cytology Myoblasts / drug effects Organ Specificity / drug effects Receptor Protein-Tyrosine Kinases / metabolism Signal Transduction / drug effects Transcription, Genetic / drug effects Volatilization Vulva / drug effects Vulva / embryology p120 GTPase Activating Protein / metabolism* ras GTPase-Activating Proteins / metabolism ras Proteins / metabolism
IF 2.896
引用数 8
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
線虫 tm748