Modulation of human c-mpl gene expression by thrombopoietin through protein kinase C.
The c-Mpl, thrombopoietin (TPO) receptor specificially controls megakaryocytic growth and differentiation. TPO increased the c-mpl promoter activity determined by a transient expression system using a vector containing the luciferase gene as a reporter in the human megakaryoblastic cell line CMK. The maximal promoter activity of c-mpl was obtained 24 hr after pretreatment with TPO for 3 hr and then declined with time. This increase was completely abolished by protein kinase C (PKC) inhibitors (GF109203, calphostin C and H7). Phorbol 12-myristate 13-acetate (PMA) treatment led to an increase in c-mpl promoter activity. These results demonstrate that the promoter activity of c-mpl is modulated by transcription through a PKC-dependent pathway.
Department of Safety Research on Blood Products and Biologics, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
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Sunohara
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Morikawa
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Sato
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D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000494:pharmacology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D015240:Phorbol 12,13-Dibutyrate; D013926:Thrombopoietin; D011493:Protein Kinase C