Interleukin 3-dependent survival by the Akt protein kinase.
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.
Songyang
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Z
Department of Biology, Massachusetts Institute of Technology, 68-380, Cambridge, MA 02139, USA. zsongyan@mit.edu
Baltimore
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Cantley
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Kaplan
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Franke
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D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D017077:Culture Media, Conditioned; D004249:DNA Damage; D005047:Etoposide / Q000633:toxicity; D007377:Interleukin-3 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D014162:Transfection
D017077:Culture Media, Conditioned; D005047:Etoposide; D007377:Interleukin-3; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D013936:Thymidine