| Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex. | |
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MedLine Citation:
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PMID: 17183368 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Mary Y W Wu; Megan Cully; Ditte Andersen; Sally J Leevers |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-21 |
Journal Detail:
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Title: The EMBO journal Volume: 26 ISSN: 0261-4189 ISO Abbreviation: EMBO J. Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2007-01-24 Completed Date: 2007-03-27 Revised Date: 2010-02-01 |
Medline Journal Info:
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Nlm Unique ID: 8208664 Medline TA: EMBO J Country: England |
Other Details:
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Languages: eng Pagination: 371-9 Citation Subset: IM |
Affiliation:
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Growth Regulation Laboratory, Cancer Research UK London Research Institute, London, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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metabolism* Animals Cell Division / drug effects* Cell Proliferation / drug effects Cells, Cultured Drosophila Drosophila Proteins / metabolism* G2 Phase / drug effects* Insulin / pharmacology* Intracellular Signaling Peptides and Proteins / metabolism* Male Multiprotein Complexes / metabolism RNA Interference S Phase / drug effects Signal Transduction Wing / cytology, drug effects |
| Chemical | |
Reg. No./Substance:
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0/Drosophila Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Multiprotein Complexes; 0/Raptor protein, Drosophila; 11061-68-0/Insulin; EC 2.7.1.-/target of rapamycin protein, Drosophila; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase |
| Comments/Corrections | |
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