EPIDERMAL GROWTH-FACTOR INDUCTION OF THE C-JUN PROMOTER BY A RAC PATHWAY

The c-jun proto-oncogene encodes a transcription factor which is activ ated by mitogens both transcriptionally and by phosphorylation by Jun N-terminal kinase (JNK). We have investigated the cellular signalling pathways involved in epidermal growth factor (EGF) induction of the c- jun promoter. We find that two sequence elements, which bind ATF1 and MEF2D transcription factors, are required in HeLa cells, although they are not sufficient for maximal induction. Activated forms of Ras, Rac I, Cdc42Hs, and MEKK increased expression of the c-jun promoter, while dominant negative forms of Ras, RacI, and MEK kinase (MEKK) inhibited EGF induction. These and previously published results suggest that EG F activates the c-jun promoter by a Ras-to-Rac-to-MEKK pathway. This p athway is similar to that used for posttranslational activation of c-j un by JNK.