Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10816624 | Cellular Signalling | 2005 | 15 Pages |
Abstract
We have examined the role of phosphoinositide 3-kinases (PI3K) in interleukin (IL)-3-dependent cell cycle progression and compared the effects of LY294002 with expression of a dominant negative form of p85, termed Îp85, which more specifically inhibits class IA PI3Ks. Inhibition of PI3Ks in BaF/3 led to accumulation of cells in G1 and extension of cell cycle transit times. Biochemically, both LY294002 and Îp85 decreased levels of p107 and cyclins D2, D3 and E and reduced retinoblastoma protein (pRb) phosphorylation. Significantly, only LY294002 treatment increased expression of p27Kip1. Interestingly, LY294002 decreased IL-3-induced proliferation of primary bone marrow-derived mast cells (BMMC) derived from both wild-type and p27Kip1-deficient mice and importantly, LY294002 treatment failed to upregulate p27Kip1 in wild-type BMMC. These data support a role for class IA PI3K in regulating optimal cell cycle progression in response to IL-3 and demonstrate that upregulation of p27Kip1 is not essential for attenuation of the cell cycle resulting from PI3K inhibition.
Keywords
PRBBMMCPKBCKISCFTETP27kip1ERKXTTPI3KCDKMAPKSTATinterleukinInterleukin-3TetracyclineBone marrow-derived mast cellsM phaseS phaseStem Cell FactorFoxOPhosphoinositide 3-kinasesMast cellsSignal transducer and activator of transcriptionMEKcyclin-dependent kinase inhibitorMitosiswild typeretinoblastoma proteinprotein kinase Bmitogen-activated protein kinasePropidium iodideCell cycleextracellular-regulated kinasecyclin-dependent kinase
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Authors
Bridget C. Fox, Tracey E. Crew, Melanie J. Welham,