Abstract
Constitutive expression of the Pim-1 kinase prolongs survival of cytokine-deprived FDCP1 cells, partly via maintenance of Bcl-2 expression. Here, we show that Pim-1 colocalizes and physically interacts with the pro-apoptotic Bad protein and phosphorylates it in vitro on serine 112, which is a gatekeeper site for its inactivation. Furthermore, wild-type Pim-1, but not a kinase-deficient mutant, enhances phosphorylation of this site in FDCP1 cells and protects cells from the pro-apoptotic effects of Bad. Our results suggest that phosphorylation of Bad by Pim-1 is one of several mechanisms via which the Pim-1 kinase can enhance Bcl-2 activity and promote cell survival.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / physiology*
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COS Cells
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Carrier Proteins / antagonists & inhibitors*
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Carrier Proteins / metabolism
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Cell Survival / drug effects
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Cell Survival / physiology
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Chlorocebus aethiops
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Interleukin-3 / pharmacology
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Kinetics
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Phosphorylation
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Phosphoserine / metabolism*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-pim-1
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Recombinant Fusion Proteins / metabolism
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Transfection
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bcl-Associated Death Protein
Substances
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Carrier Proteins
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Interleukin-3
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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bcl-Associated Death Protein
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Phosphoserine
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Glutathione Transferase
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-pim-1