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EMBO J ; 26(2): 371-9, 2007 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-17183368

RESUMEN

In Drosophila and mammals, insulin signalling can increase growth, progression through G1/S, cell size and tissue size. Here, we analyse the way insulin affects cell size and cell-cycle progression in two haemocyte-derived Drosophila cell lines. Surprisingly, we find that although insulin increases cell size, it slows the rate at which these cells increase in number. By using BrdU pulse-chase to label S-phase cells and follow their progression through the cell cycle, we show that insulin delays progression through G2/M, thereby slowing cell division. The ability of insulin to slow progression through G2/M is independent of its ability to stimulate progression through G1/S, so is not a consequence of feedback by the cell-cycle machinery to maintain cell-cycle length. Insulin's effects on progression through G2/M are mediated by dTOR/dRaptor signalling. Partially inhibiting dTOR/dRaptor signalling by dsRNAi or mild rapamycin treatment can increase cell number in cultured haemocytes and the Drosophila wing, respectively. Thus, insulin signalling can influence cell number depending on a balance between its ability to accelerate progression through G1/S and delay progression through G2/M.


Asunto(s)
División Celular/efectos de los fármacos , Proteínas de Drosophila/metabolismo , Fase G2/efectos de los fármacos , Insulina/farmacología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Drosophila , Masculino , Complejos Multiproteicos/metabolismo , Proteínas Quinasas , Interferencia de ARN , Fase S/efectos de los fármacos , Transducción de Señal , Serina-Treonina Quinasas TOR , Alas de Animales/citología , Alas de Animales/efectos de los fármacos
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