Role of the Raf Signal Transduction Pathway in Fos/Jun Regulation and Determination of Cell Fates
Raf kinases are essential for induced growth and several developmental pathways. These enzymes function by activating a protein kinase cascade that culminates in the phosphorylation of oncogene class transcription factors while simultaneously integrating pathways of energy metabolism. As there are many growth factors that regulate Raf kinases, activated growth factor receptors such as the platelet derived growth factor (PDGF) receptor make contact with a large number of cellular candidate second messenger proteins. Fos and Jun and most of their regulators were originally identified as oncogenes. Identification of the signal transduction pathways involved in relieving negative regulation of Fos and Jun family members awaits further investigation. The dominant negative mutant of c-Jun strongly inhibited the establishment of transformation by representatives of all classes of oncogenes, as judged from two types of focus reduction assays, cotransfection, and virus titration.