Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases (original) (raw)

1994, Proceedings of the National Academy of Sciences

c-Jun trcriptional activity is augmented by expression of oncogenic Ras and Raf proteins. This study demonstrates a direct correlation between Ras tAsfom activity and c-Jun activation, s ing an Imprnt role for c-Jun in tsfor by Ras. Since we observed that Ras activated c-Jun trarIptinal activit by in sing phos phorylation of the c-Jun activation domain at residues Ser-63/ Ser-73 and that icRas proteins activated extracellular signal-regulated protein ka (ERK1 and ERK2) (also known as mit-activated protein kiass), we evaluated the possibity that ERKs were dlrectly responsible for c-Jun activation. Coexpresson ofwild-type ERKs with oncogenic Ras proteins potentiated, while Dasdefective ERKs inhibited, Ras-Induced taitonlvation from the Ras-responsive element (Etsa-/AP-i) present in the NVL-3 enhancer and the serum-response element in the c-fos promoter. In contrat, coexpresslon of either wild-type or kinase-defective ERKs inhibited Ras and Rat activation of c-Jun transcriptional activty Thus, although activation of both ERK and c-Jun are downstream consequences of activation of the Ras signal transduction pathway, our results suggest that Ras-induced c-Jun phosphorylation and transcriptional activation are not a direct consequence of ERK1 and ERK2 activation.