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We analyzed the effects of insulin-like growth factor-I (IGF-I), a polypeptide growth factor which exerts mitogenic effects via specific membrane receptors. The control of IGF-I on c-fosand c-juntranscription was studied in PC12 cells. Gel mobility shift assays with a labeled AP1 consensus binding sequence (TRE: TGACTCA) showed an increase in specific binding upon trIGF-I treatment. Gene transfer studies revealed that the increase in API binding is functional since IGF-I stimulates transcription from a reporter gene containing the minimal TRE linked to the chloramphenicol acetyl transferase (CAT) reporter gene. To further characterize the molecular mechanism by which IGF-I increases API activity, we analysed the transcription regulation of c-fosand c-junusing reporter genes containing the respective promoters or specific regulatory elements. Deletion studies with the c-junpromoter, showed that IGF-I stimulates c-juntranscription via a cisacting element(s) localized within the 132 base pairs prior to the transcription start site; possibly the API like element TGACATCA. Similar studies revealed that c-fosstimulation by IGF-I requires the presence of a regulatory sequence spanning the dyad symmetry element (DSE) and the fos AP1-like sequence (FAP). Further experiments using specific elements linked to the minimal unresponsive c-fospromoter, showed that the DSE is the main target for c-fosinduction by IGF-I.