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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
1991-4-23
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pubmed:abstractText |
Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the growth and differentiation of human hematopoietic progenitor cells by activating transcription of specific genes. The mechanism by which binding of GM-CSF to its receptor stimulates gene expression remains unknown. To examine this process in more detail, we have transfected human monocytic leukemia cells U937 with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase recorder gene and treated them with GM-CSF. We find that GM-CSF stimulates a 2-3-fold increase in chloramphenicol acetyltransferase activity over a concentration range 1-1,000 units/ml. Northern and Western blot analysis demonstrates that the mechanism by which GM-CSF stimulates AP-1 enhancer activity involves increases in c-jun and c-fos mRNA levels, and increases in Jun protein. In a similar fashion the treatment of normal human monocytes with GM-CSF also induced increases in total cellular c-jun. Because protein kinase C plays a crucial role in activating c-jun transcription we examined the role of this enzyme in mediating the effects of GM-CSF. Treatment of U937 cells with inhibitors of protein kinase C including staurosporine 10 nM and H-7 50 microM, or down-regulation of protein kinase C by phorbol ester pretreatment blocks the induction of c-jun by GM-CSF. However, HA which does not block protein kinase C had no effect on GM-CSF stimulation of c-jun RNA levels. In addition, GM-CSF treatment causes the rapid translocation of protein kinase C to the particulate fraction which was maximal by 5 min and returned to base line by 80 min. These data suggest that the binding of GM-CSF to its receptor stimulates increases in c-jun mRNA and protein and activates AP-1 enhancer activity. These effects may be at least in part mediated by activation of protein kinase C.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaloids,
http://linkedlifedata.com/resource/pubmed/chemical/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
266
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pubmed:geneSymbol |
c-jun
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5670-5
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:1900839-Alkaloids,
pubmed-meshheading:1900839-Base Sequence,
pubmed-meshheading:1900839-Blotting, Northern,
pubmed-meshheading:1900839-Blotting, Western,
pubmed-meshheading:1900839-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:1900839-DNA-Binding Proteins,
pubmed-meshheading:1900839-Gene Expression Regulation,
pubmed-meshheading:1900839-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:1900839-Humans,
pubmed-meshheading:1900839-Molecular Sequence Data,
pubmed-meshheading:1900839-Plasmids,
pubmed-meshheading:1900839-Protein Kinase C,
pubmed-meshheading:1900839-Proto-Oncogene Proteins,
pubmed-meshheading:1900839-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:1900839-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:1900839-RNA, Messenger,
pubmed-meshheading:1900839-Staurosporine,
pubmed-meshheading:1900839-Tetradecanoylphorbol Acetate,
pubmed-meshheading:1900839-Transcription, Genetic,
pubmed-meshheading:1900839-Transcription Factors,
pubmed-meshheading:1900839-Tumor Cells, Cultured
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pubmed:year |
1991
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pubmed:articleTitle |
Regulation of c-jun expression and AP-1 enhancer activity by granulocyte-macrophage colony-stimulating factor.
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pubmed:affiliation |
Division of Hematology/Oncology, University of Alabama, Birmingham 35294.
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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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