INDUCTION OF FOS AND JUN PROTEINS BY ADRENOCORTICOTROPIN AND PHORBOL ESTER BUT NOT BY 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE DERIVATIVES

We report the results of an extensive kinetic analysis of the effects of ACTH, cAMP derivatives (dibutyryl cAMP and 8-bromo-cAMP) and phorbo l ester (phorbol-12-myristate-13-acetate) on the expression of fos and jun gene family members at the mRNA (Northern hybridization) and prot ein levels (immunoprecipitation and indirect immunofluorescence) in th e mouse Y-1 adrenocortical cell line. FOS and JUN proteins are induced by ACTH independently of cell cycle stage. c-Fos, fos-B, fra-1, fra-2 , c-jun, and jun-B genes are induced by ACTH, the kinetic profiles for mRNAs and respective protein products being similar, except for a 1-h protein delay. Jun-D mRNA is an exception, being constitutively expre ssed. However, JUN D protein is induced by ACTH. phorbol-12-myristate- 13-acetate closely mimics these inductive effects of ACTH. On the othe r hand, cAMP derivatives are not effective in inducing the fos and jun genes, except for fra-2 mRNA, JUN D protein, and to some extent JUN B protein. Clearly, ACTH is endowed with the versatile capability of mo dulating fos and jun gene expression, suggesting that AP-1 transcripti on factors play a role in ACTH mechanisms of action. ACTH receptors ar e likely to activate signaling routes other than the classical cAMP/pr otein kinase A in order to induce FOS and JUN proteins.