Modulation mechanism of c-Mpl promoter activity in megakaryoblastic cells.

Thrombopoietin receptor (c-Mpl) is considered to regulate megakaryocytopoiesis. In this study, we investigated an effect of activation of a protein kinase C (PKC) on c-mpl promoter activity to elucidate the underlying mechanisms of c-mpl gene expression in megakaryoblastic cells. PKC is a member of a family of serine/threonine protein kinases in the cytosol involved in cell growth and differentiation. Phorbol 12-myristate 13-acetate (PMA) is known as PKC activator, significantly enhanced the c-mpl promoter activity and PKC inhibitors (H7, GF109203) suppressed the up-regulation of PMA-induced promoter activity and reduced the steady level of its activity. These results strongly suggest that PKC plays the essential role in the modulation of c-mpl promoter activity of megakaryoblastic cells.