| First Author | Miltenberger RJ | Year | 1993 |
| Journal | J Biol Chem | Volume | 268 |
| Issue | 21 | Pages | 15674-80 |
| PubMed ID | 8340392 | Mgi Jnum | J:14199 |
| Mgi Id | MGI:62373 | Doi | 10.1016/s0021-9258(18)82309-2 |
| Citation | Miltenberger RJ, et al. (1993) An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes. J Biol Chem 268(21):15674-80 |
| abstractText | The proto-oncogene Raf-1 is a cytoplasmic serine/threonine kinase implicated in the signaling process in cell proliferation. To determine if Raf-1 is sufficient and necessary to transmit mitogenic signals to growth-responsive genes, we examined the effect of constitutively activated (v-raf) or inhibitory (Raf-C4) Raf-1 proteins on reporter gene activation in transient expression assays of NIH 3T3 cells. In serum-starved cells, v-raf strongly activated transcription from the promoters of the immediate-early genes c-fos and egr-2, as well as the proximal or B promoter of the late growth response gene rep-3 (rep-3b). Two other late response gene promoters, cad and dhfr, were only modestly activated by v-raf, however. An individual serum response element from the c-fos or egr-2 promoter conferred both serum-inducibility and v-raf-responsiveness to a heterologous promoter. Consistent with the degree to which antisense c-raf-1 RNA and dominant-negative Raf-1 proteins interfere with NIH 3T3 cell proliferation, Raf-C4 reduced serum-induced transcription from the egr-2 and rep-3b promoters in a dose-dependent manner by 50%. In contrast, Raf-C4 did not significantly reduce transcription from the c-fos or cad promoters or the serum response element-driven heterologous promoters. We conclude that Raf-1 is both sufficient and necessary to activate a subset of early and late growth response genes. |
