TRANSACTIVATION OF THE TPA-RESPONSIVE ELEMENT BY THE ONCOGENIC-C-ERBB-2 PROTEIN IS PARTLY MEDIATED BY PROTEIN-KINASE-C

The mutant c-erbB-2 gene encoding a protein with Glu instead of Val-659 in the transmembrane domain is able to transform NIH3T3 cells, while the wild type c-erbB-2 unless overexpressed does not. The mutant c-erbB-2 protein shows enhanced tyrosine kinase activity in vitro. Transient expression of this active c-erbB-2 stimulated the 12-O-tetradecanoylphorbol-13-acetate (TPA) response element, serum response element, and cyclic AMP response element. Particularly, stimulation of the TPA response element by active c-erbB-2 was prominent. In contrast, transient expression of wild type c-erbB-2 stimulated none of these elements. Transactivation of the TPA response element was also observed in a cell line that stably expresses active c-erbB-2. The active c-erbB-2-induced transactivation of the TPA response element was partially prevented either by down-regulation of protein kinase C or by the protein kinase C inhibitor H7. These results indicate that protein kinase C is partly involved in oncogenic signalling of the active c-erbB-2 protein that leads to Jun Fos-mediated transcriptional activation in nuclei. © 1991.