RRC ID 22714
著者 Montagne J, Lecerf C, Parvy JP, Bennion JM, Radimerski T, Ruhf ML, Zilbermann F, Vouilloz N, Stocker H, Hafen E, Kozma SC, Thomas G.
タイトル The nuclear receptor DHR3 modulates dS6 kinase-dependent growth in Drosophila.
ジャーナル PLoS Genet
Abstract S6 kinases (S6Ks) act to integrate nutrient and insulin signaling pathways and, as such, function as positive effectors in cell growth and organismal development. However, they also have been shown to play a key role in limiting insulin signaling and in mediating the autophagic response. To identify novel regulators of S6K signaling, we have used a Drosophila-based, sensitized, gain-of-function genetic screen. Unexpectedly, one of the strongest enhancers to emerge from this screen was the nuclear receptor (NR), Drosophila hormone receptor 3 (DHR3), a critical constituent in the coordination of Drosophila metamorphosis. Here we demonstrate that DHR3, through dS6K, also acts to regulate cell-autonomous growth. Moreover, we show that the ligand-binding domain (LBD) of DHR3 is essential for mediating this response. Consistent with these findings, we have identified an endogenous DHR3 isoform that lacks the DBD. These results provide the first molecular link between the dS6K pathway, critical in controlling nutrient-dependent growth, and that of DHR3, a major mediator of ecdysone signaling, which, acting together, coordinate metamorphosis.
巻・号 6(5)
ページ e1000937
公開日 2010-5-6
DOI 10.1371/journal.pgen.1000937
PMID 20463884
PMC PMC2865512
MeSH Animals Drosophila / chemistry Drosophila / genetics Drosophila / growth & development* Drosophila / metabolism* Drosophila Proteins / chemistry Drosophila Proteins / genetics Drosophila Proteins / metabolism* Female Gene Expression Regulation, Developmental Male Metamorphosis, Biological Protein Structure, Tertiary Receptors, Cytoplasmic and Nuclear / chemistry Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Ribosomal Protein S6 Kinases / genetics Ribosomal Protein S6 Kinases / metabolism* Signal Transduction
IF 5.175
引用数 11
WOS 分野 GENETICS & HEREDITY
リソース情報
ショウジョウバエ 12208R-2 12208R-3