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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2001-6-6
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pubmed:abstractText |
Polymorphonuclear neutrophils (PMN) are phagocytic cells constitutively programmed for apoptotic cell death. Exposure to GM-CSF delays apoptosis as measured by annexin-V staining and cell morphological change. We found that STAT5B, STAT1, and STAT3 DNA-binding activity was induced by GM-CSF. We also detected activation of the phosphatidylinositol 3-kinase (PI 3-kinase) pathway after GM-CSF treatment which was inhibited by treatment with the PI 3-kinase inhibitors, wortmannin and LY294002. We investigated whether STAT or PI 3-kinase activity was necessary for the pro-survival response of GM-CSF in PMN. Exposure of PMN to GM-CSF in the presence of either AG-490, antisense STAT3 oligonucleotides, or wortmannin resulted in a partial inhibition of GM-CSF-mediated pro-survival activity. GM-CSF induced a time-dependent increase in the mRNA and protein expression of the anti-apoptotic Bcl-2-family protein, Mcl-1. We examined the hypothesis that Janus kinase/STAT and PI 3-kinase regulation of Mcl-1 contributed to GM-CSF-delayed apoptosis. Using either AG-490 or wortmannin alone, we observed a dose-dependent inhibition of GM-CSF-induced Mcl-1 expression. Using suboptimal doses of AG-490 and wortmannin, we found that both drugs together had an additive effect on delayed apoptosis and Mcl-1 expression. These data suggest that cooperative regulation of Mcl-1 by the Janus kinase/STAT and PI 3-kinase pathways contribute to GM-CSF-delayed apoptosis.
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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 |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-cyano-(3,4-dihydroxy)-N-benzyl...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
166
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7486-95
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11390502-Apoptosis,
pubmed-meshheading:11390502-Cell Survival,
pubmed-meshheading:11390502-Cells, Cultured,
pubmed-meshheading:11390502-DNA-Binding Proteins,
pubmed-meshheading:11390502-Drug Synergism,
pubmed-meshheading:11390502-Enzyme Inhibitors,
pubmed-meshheading:11390502-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11390502-Humans,
pubmed-meshheading:11390502-Janus Kinase 1,
pubmed-meshheading:11390502-Janus Kinase 2,
pubmed-meshheading:11390502-Janus Kinase 3,
pubmed-meshheading:11390502-Kinetics,
pubmed-meshheading:11390502-Neoplasm Proteins,
pubmed-meshheading:11390502-Neutrophils,
pubmed-meshheading:11390502-Oligonucleotides, Antisense,
pubmed-meshheading:11390502-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11390502-Precipitin Tests,
pubmed-meshheading:11390502-Protein-Tyrosine Kinases,
pubmed-meshheading:11390502-Proto-Oncogene Proteins,
pubmed-meshheading:11390502-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11390502-RNA, Messenger,
pubmed-meshheading:11390502-STAT3 Transcription Factor,
pubmed-meshheading:11390502-Signal Transduction,
pubmed-meshheading:11390502-Trans-Activators,
pubmed-meshheading:11390502-Tyrphostins,
pubmed-meshheading:11390502-bcl-2-Associated X Protein
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pubmed:year |
2001
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pubmed:articleTitle |
Cooperative regulation of Mcl-1 by Janus kinase/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils.
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pubmed:affiliation |
Hematologic Malignancy Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, FL 33612, USA. burnetpk@moffit.usf.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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