Activation of Jun/AP-1 by protein kinase A.
The product of the c-jun proto-oncogene is the major component of the 12-O-tetradecanoyl phorbol 13-acetate (TPA)-inducible transcription factor AP-1. Jun binds to the TPA-responsive elements (TREs) present in a large number of TPA-inducible genes, thereby regulating their expression in response to activation of protein kinase C. Previously we have shown that Jun/AP-1 can also activate cAMP-responsive elements (CREs), indicating the existence of cross-talk in signal transduction at the transcriptional level. Here we show that Jun/AP-1 is activated by the cAMP-dependent protein kinase A (PKA). In transient transfection experiments, TRE activation by Jun is strongly enhanced by co-transfection of the catalytic subunit of PKA or forskolin treatment, although not in all cell types studied. Jun activity can be significantly inhibited by co-transfection of the regulatory subunit of PKA. Furthermore, we show a cell-specific increase in AP-1 binding in response to forskolin treatment. However, since direct phosphorylation of Jun by PKA does not occur, we suggest an indirect activation mechanism.
de Groot
R P
RP
Laboratoire de Génétique Moléculaire des Eucaryotes, CNRS, U184 de l'INSERM, Faculté de Médecine, Strasbourg, France.
Sassone-Corsi
P
P
D000818:Animals; D001483:Base Sequence; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D004247:DNA; D000242:Cyclic AMP; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate