The c-fos serum response element responds to protein kinase C-dependent ano-lndependent signals but not to cyclic AMP

Transcription of the c-fos proto-oncogene is rapidly induced by serum growth factors. A short c-fos DNA element, the serum response element (SRE), is required for this response to serum. However, serum activates a series of distinct intracellular signaling pathways, and it is not known to which of these pathways the SRE responds. To address this question, mutations have been introduced into the SRE of an otherwise intact c-fos promoter/enhancer. These mutations strongly reduce the binding of a nuclear factor to this site. Plasmids carrying either a wild-type or mutant c-fos SRE were transfected into fibroblasts and tested for their response to whole serum, purified recombinant c-sis protein, the protein kinase C activator phorbol myristate acetate, and activators of the cyclic AMP (cAMP) second messenger system. Assays were carried out under normal conditions and after chronic phorbol ester-treatment to deplete phorbol ester activatable protein kinase C activity from transfected cells. The results show that the SRE is necessary and sufficient for response to both protein kinase C--dependent and-independent intracellular signaling pathways but not for response to the cAMP pathway.