The major regulators of the c‐jun promoter are ATF‐2 and c‐Jun. They act as pre‐bound heterodimers on two ‘AP‐1‐like’ sites, and are preferentially addressed by different types of extracellular signals. The transactivating potential of ATF‐2 is stimulated to a higher extent than that of c‐Jun by a broad group of agents causing DNA damage and other types of cellular stress, such as short‐wavelength UV, or the alkylating compounds N‐methyl‐N’‐nitro‐N‐nitroso‐guanidine (MNNG) or methylmethanesulphonate (MMS). In contrast, treatment with the phorbol ester TPA preferentially enhances c‐Jun‐dependent transactivation but does not affect ATF‐2. Accordingly, UV and MMS but not TPA induce c‐jun transcription in F9 cells, which express ATF‐2, but not c‐Jun. Stimulation of ATF‐2‐dependent transactivation by genotoxic agents requires the presence of threonines 69 and 71 located in the N‐terminal transactivation domain. These sites are the target of p54 and p46 stress‐activated protein kinases (SAPKs) which bind to, and phosphorylate ATF‐2 in vitro. However, p46 and p54 kinase activity is not increased by phorbol ester, which strongly suggests that the protein kinase phosphorylating c‐Jun in response to TPA is distinct from SAPKs and does not act on ATF‐2. Our data demonstrate that distinct signal transduction pathways converge at c‐Jun/ATF‐2, whereby each subunit is individually addressed by a specific class of protein kinases. This allows fine tuned modulation of c‐jun expression by a large spectrum of extracellular signals.