Abstract
Interleukin 3 (IL-3)-dependent survival of hematopoietic cells is known to rely on the activity of multiple signaling pathways, including a pathway leading to activation of phosphoinositide 3-kinase (PI 3-kinase), and protein kinase Akt is a direct target of PI 3-kinase. We find that Akt kinase activity is rapidly induced by the cytokine IL-3, suggesting a role for Akt in PI 3-kinase-dependent signaling in hematopoetic cells. Dominant-negative mutants of Akt specifically block Akt activation by IL-3 and interfere with IL-3-dependent proliferation. Overexpression of Akt or oncogenic v-akt protects 32D cells from apoptosis induced by IL-3 withdrawal. Apoptosis after IL-3 withdrawal is accelerated by expression of dominant-negative mutants of Akt, indicating that a functional Akt signaling pathway is necessary for cell survival mediated by the cytokine IL-3. Thus Akt appears to be an important mediator of anti-apoptotic signaling in this system.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division
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Cell Line
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Cell Survival / drug effects
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Cell Survival / physiology*
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Culture Media, Conditioned
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DNA Damage
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Etoposide / toxicity
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Interleukin-3 / pharmacology*
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Kinetics
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Mice
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Oncogene Protein v-akt
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Retroviridae Proteins, Oncogenic / biosynthesis
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Retroviridae Proteins, Oncogenic / metabolism*
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Signal Transduction
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Thymidine / metabolism
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Transfection
Substances
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Culture Media, Conditioned
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Interleukin-3
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Proto-Oncogene Proteins
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Recombinant Proteins
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Retroviridae Proteins, Oncogenic
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Etoposide
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Protein-Tyrosine Kinases
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Oncogene Protein v-akt
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Thymidine