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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2003-11-10
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pubmed:abstractText |
Hematopoietic growth factors mediate the survival and proliferation of blood-forming cells, but the mechanisms through which these proteins produce their effects are incompletely known. Recent studies have identified the pim family of kinases as mediators of cytokine-dependent survival signals. Several studies have identified substrates for the pim-1 kinase, but little is known about the other family members, pim-2 and pim-3. We have investigated potential functions for the pim-2 kinase in factor-dependent murine hematopoietic cells. We find that pim-2 mRNA and protein expression are regulated by cytokines similarly to pim-1. Three PIM-2 protein isoforms are produced in cytokine-treated cells. All three forms are active kinases, and the short (PIM-2(34 kDa)) form is the most active at enhancing survival of FDCP1 cells after cytokine withdrawal. This pro-survival function involves inhibition of apoptosis and caspase activation. Enforced expression of PIM-2(34 kDa) kinase does not appear to regulate expression of BCL-2, BCL-xL, BIM, or BAX proteins. However, the kinase can phosphorylate the pro-apoptotic protein BAD on serine 112, which accounts in part for its ability to reverse Bad-induced cell death. Our results indicate that pim-2 functions similarly to pim-1 as a pro-survival kinase and suggest that BAD is a legitimate PIM-2 substrate.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/BAD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/PIM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pim2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45358-67
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12954615-Animals,
pubmed-meshheading:12954615-Antibodies, Monoclonal,
pubmed-meshheading:12954615-Apoptosis,
pubmed-meshheading:12954615-Blotting, Northern,
pubmed-meshheading:12954615-Blotting, Western,
pubmed-meshheading:12954615-Carrier Proteins,
pubmed-meshheading:12954615-Cell Line,
pubmed-meshheading:12954615-Cell Line, Tumor,
pubmed-meshheading:12954615-Cell Survival,
pubmed-meshheading:12954615-Cycloheximide,
pubmed-meshheading:12954615-Cytokines,
pubmed-meshheading:12954615-DNA, Complementary,
pubmed-meshheading:12954615-Glutathione Transferase,
pubmed-meshheading:12954615-HeLa Cells,
pubmed-meshheading:12954615-Humans,
pubmed-meshheading:12954615-Interleukin-3,
pubmed-meshheading:12954615-Jurkat Cells,
pubmed-meshheading:12954615-Kinetics,
pubmed-meshheading:12954615-Mice,
pubmed-meshheading:12954615-NIH 3T3 Cells,
pubmed-meshheading:12954615-Phosphorylation,
pubmed-meshheading:12954615-Plasmids,
pubmed-meshheading:12954615-Protein Isoforms,
pubmed-meshheading:12954615-Protein Synthesis Inhibitors,
pubmed-meshheading:12954615-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12954615-Proto-Oncogene Proteins,
pubmed-meshheading:12954615-RNA, Messenger,
pubmed-meshheading:12954615-Serine,
pubmed-meshheading:12954615-Time Factors,
pubmed-meshheading:12954615-Transfection,
pubmed-meshheading:12954615-Transgenes,
pubmed-meshheading:12954615-bcl-Associated Death Protein
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pubmed:year |
2003
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pubmed:articleTitle |
The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death.
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pubmed:affiliation |
Center for Molecular Biology & Gene Therapy, the Department of Microbiology, Loma Linda University School of Medicine, Loma Linda, California 92354, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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