Thrombopoietin is the cytokine involved in megakaryopoiesis and its receptor (c-Mpl) is considered to regulate development of megakaryocyte. In this research, to elucidate the underlying mechanisms of c-mpl gene expression in megakaryoblastic cells, we investigated the effect of a protein kinase C (PKC) on c-mpl promoter activity in a time-dependent manner. 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 inhibitor, 2-methylpiperazine dihydrochloride (H-7) suppressed the up-regulation of PMA-induced promoter activity and this effect decreased in a time-dependent manner. These results clearly suggest that in megakaryoblastic cells, PKC plays the crucial role in the initiation of up-regulation of PMA-induced c-mpl promoter activity.