Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Protects against Interleukin-3 Starvation but Not DNA Damage-induced Apoptosis

Baf-3 cells are dependent on interleukin-3 (IL-3) for their survival and proliferation in culture. To identify anti-apoptotic pathways, we performed a retroviral-insertion mutagenesis on Baf-3 cells and selected mutants that have acquired a long term survival capacity. The phenotype of one mutant, w...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-04, Vol.276 (14), p.10935-10942
Main Authors: Mathieu, Anne-Laure, Gonin, Sandrine, Leverrier, Yann, Blanquier, Bariza, Thomas, Joëlle, Dantin, Carole, Martin, Guy, Baverel, Gabriel, Marvel, Jacqueline
Format: Article
Language:English
Subjects:
Akt protein
Animals
Apoptosis - genetics
Bcl-x protein
Cell Division - genetics
Cell Line
Cell Survival - genetics
DNA Damage
Enzyme Activation
Humans
Interleukin-3 - deficiency
Interleukin-3 - genetics
Mutation
Phosphatidylinositol 3-Kinases - genetics
Phosphatidylinositol 3-Kinases - metabolism
Phosphorylation
Signal Transduction
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Summary:Baf-3 cells are dependent on interleukin-3 (IL-3) for their survival and proliferation in culture. To identify anti-apoptotic pathways, we performed a retroviral-insertion mutagenesis on Baf-3 cells and selected mutants that have acquired a long term survival capacity. The phenotype of one mutant, which does not overexpress bcl-x and proliferates in the absence of IL-3, is described. We show that, in this mutant, Akt is constitutively activated leading to FKHRL1 phosphorylation and constitutive glycolytic activity. This pathway is necessary for the mutant to survive following IL-3 starvation but is not sufficient or necessary to protect cells from DNA damage-induced cell death. Indeed, inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in Baf-3 cells does not prevent the ability of IL-3 to protect cells against γ-irradiation-induced DNA damage. This protective effect of IL-3 rather correlates with the expression of the anti-apoptotic Bcl-x protein. Taken together, these data demonstrate that the PI3K/Akt pathway is sufficient to protect cells from growth factor starvation-induced apoptosis but is not required for IL-3 inhibition of DNA damage-induced cell death.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M007147200