Abstract
Growth factor withdrawal results in the termination of factor-dependent transcription. One transcript that declines rapidly following growth factor deprivation of hematopoietic cells is the serine/threonine kinase pim-2. When constitutively expressed, Pim-2 conferred long-term resistance to a variety of apoptotic stimuli including growth factor withdrawal and endogenous levels of Pim-2 contributed to growth factor-mediated apoptotic resistance. Pim-2 expression maintained cell size and mitochondrial potential independently of the PI3K/Akt/TOR pathway. Pim-2-dependent maintenance of cell size and survival correlated with its ability to maintain rapamycin-resistant phosphorylation of the translational repressor 4E-BP1 and phosphorylation of the BH3 protein BAD. These results establish Pim-2 as a direct link between growth factor-induced transcription and a novel, kinase-dependent pathway that promotes cell-autonomous survival.
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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Antibiotics, Antineoplastic / pharmacology
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Apoptosis*
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Blotting, Northern
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Blotting, Western
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Cell Division
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Cell Line
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Cell Survival
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Dose-Response Relationship, Drug
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Flow Cytometry
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Gene Expression Regulation
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Genetic Vectors
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Glucose / metabolism
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Glucose / pharmacology
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Interleukin-3 / metabolism
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Lactates / metabolism
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Membrane Potentials
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Mice
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Mitochondria / metabolism
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Oligonucleotide Array Sequence Analysis
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Phenotype
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Phosphorylation
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Plasmids / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / physiology*
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Recombinant Proteins / metabolism
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Signal Transduction
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Sirolimus / pharmacology
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Staurosporine / pharmacology
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Thapsigargin / pharmacology
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Time Factors
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Transcription, Genetic*
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Transgenes
Substances
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Antibiotics, Antineoplastic
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Interleukin-3
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Lactates
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Pim2 protein, mouse
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Proto-Oncogene Proteins
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Recombinant Proteins
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Thapsigargin
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Protein Serine-Threonine Kinases
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Staurosporine
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Glucose
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Sirolimus