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  • The EMBO Journal (2007) 26, 371 - 379
  • doi:10.1038/sj.emboj.7601487

Published online: 21 December 2006

Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex

Mary YW Wu1, Megan Cully2, Ditte Andersen3 and Sally J Leevers1

  1. Growth Regulation Laboratory, Cancer Research UK London Research Institute, London, UK
  2. Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK
  3. Apoptosis and Proliferation Control Laboratory, Cancer Research UK London Research Institute, London, UK

Correspondence to:

Sally J Leevers, Growth Regulation Laboratory, Cancer Research UK London Research Institute, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel.: +44 20 7269 3240; Fax: +44 20 7269 3479; E-mail: sally.leevers@cancer.org.uk

Received 27 June 2006; Accepted 10 November 2006

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.

  • Keywords:

    • cell-cycle progression,
    • cell division,
    • G2–M transition,
    • insulin,
    • TOR