Blood 1998,
PMID: 9657746
Zauli, G; Gibellini, D; Vitale, M; Secchiero, P; Celeghini, C; Bassini, A; Pierpaoli, S; Marchisio, M; Guidotti, L; Capitani, S
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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Text Mining Data
CREB-PSer133 → TPO: "
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
"
CREB → TPO: "
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
"
Manually curated Databases
No curated data.