Transactivation of c-fos and beta-actin genes by raf as a step in early response to transmembrane signals.

A primary response to many growth factor-induced transmembrane signals is the rapid activation of transcription of the proto-oncogene c-fos and other early-response genes, including the beta-actin gene. The c-raf gene encodes a cytoplasmic serine/threonine kinase, raf-1, whose activity is also responsive to transmembrane signals and which in mutant form can transform cells. Here we show that in transient assays, the v-raf protein, which is a constitutively activated oncogenic counterpart of raf-1, can transactivate transcription from two early-response promoters, including the c-fos promoter from human and murine cells and the human beta-actin gene promoter. Multiple elements of the human fos promoter, including the dyad symmetry element necessary for growth-factor induction, an octanucleotide direct repeat element, and the region spanning the sequence from nucleotides -225 to -99 can all serve as targets for raf induction. The c-myc promoter and two adenovirus-2 early promoters are not induced. These findings indicate that raf kinase, when activated by a transmembrane signal or by mutation of a regulatory domain, can phosphorylate a factor(s) capable of regulating transcription of the c-fos and actin genes. The oncogenic form of raf may transform by constitutively activating early response protooncogenes such as c-fos.