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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-8-6
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pubmed:abstractText |
The addition of thrombopoietin (TPO) to HEL cells, cultured in a chemically defined serum-free medium, induced a rapid and dose-dependent phosphorylation of the transcription factor CREB on serine133 (PSer133), as detected by Western blot analysis. TPO also significantly increased the transactivation of CRE-dependent promoter, as determined in transient transfection experiments. On the other hand, neither erythropoietin (Epo; 1 to 10 U) nor hemin (10 (-7) mol/L) were able to significantly stimulate CREB-PSer133 or to activate CRE-promoter in HEL cells. Although pharmacological inhibitors of protein kinase C (chelerytrine and BIM) and protein kinase A (H-89) failed to block the TPO-mediated CREB phosphorylation, a specific inhibitor of the mitogen-activated protein kinases (PD98059) completely blocked the ability of TPO to stimulate CREB-PSer133. Moreover, PD98059 significantly decreased the ability of TPO to upregulate the surface expression of the alphaIIIbbeta3 megakaryocytic marker in HEL cells. In parallel, primary CD34+ hematopoietic cells were seeded in liquid cultures supplemented with 100 ng/mL of TPO and examined by immunofluorescence for the coexpression of alphaIIIbbeta3 and CREB-PSer133 at various time points. High levels of nuclear CREB-PSer133 were unequivocally demonstrated in alphaIIIbbeta3+ cells, including morphologically recognizable megakaryocytes. Taken together, these data suggest that CREB plays a role in modulating the expression of genes critical for megakaryocyte differentiation and that the TPO-mediated CREB phosphorylation seems to be regulated via mitogen-activated protein kinases.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD34,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombopoietin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
472-80
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9657746-Antigens, CD34,
pubmed-meshheading:9657746-Blotting, Western,
pubmed-meshheading:9657746-Cell Differentiation,
pubmed-meshheading:9657746-Cell Line,
pubmed-meshheading:9657746-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:9657746-Enzyme Inhibitors,
pubmed-meshheading:9657746-Flavonoids,
pubmed-meshheading:9657746-Flow Cytometry,
pubmed-meshheading:9657746-Hematopoietic Stem Cells,
pubmed-meshheading:9657746-Humans,
pubmed-meshheading:9657746-Megakaryocytes,
pubmed-meshheading:9657746-Phosphorylation,
pubmed-meshheading:9657746-Protein Kinase Inhibitors,
pubmed-meshheading:9657746-Protein Kinases,
pubmed-meshheading:9657746-Serine,
pubmed-meshheading:9657746-Signal Transduction,
pubmed-meshheading:9657746-Thrombopoietin
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pubmed:year |
1998
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pubmed:articleTitle |
The induction of megakaryocyte differentiation is accompanied by selective Ser133 phosphorylation of the transcription factor CREB in both HEL cell line and primary CD34+ cells.
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pubmed:affiliation |
Institute of Human Anatomy, University of Ferrara, Ferrara, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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