Promoter regulatory motifs involved in c-mpl gene expression induced by PMA

Phorbol-12-myristate-13-acetate (PMA) significantly elevated c-mpl promoter activity and the protein kinase C (PKC) inhibitors GF 109203, H7 and calphostin C conspicuously reduced the steady level of the activity. Destruction of the -107Sp1 and the -57Sp1 sites in the c-mpl promoter enhancer region resulted in decrease of the promoter activity by 49.6% and 48.2%, respectively, and destruction of -69Ets and -28Ets elements dramatically decreased the activity by 93.4% and 82.6%, respectively, while mutation of -77GATA moderately reduced the activity by 28.6%. We conclude that the expression of the c-mpl gene is modulated by transcription through a PKC-dependent pathway and that Ets elements at -69 and -28 nucleotides in front of the transcription start site are critical that Sp1(-107) and Sp1(-57) are also important and that GATA(-77) is less involved as a positive regulatory element in c-mpl gene expression induced by PMA in CMK cells.