We have shown that the transcriptional activity of the protooncogene jun (c-jun) promoter is repressed by a transcription factor, the cAMP response element-binding protein (CREB). This repression can be alleviated when CREB is phosphorylated by the catalytic subunit of protein kinase A. Repression cannot be alleviated by a mutant CREB deficient in the protein kinase A phoshorylation site (M1 CREB Ser-133 → Ala), suggesting that phosphorylation of CREB at this site is essential for the relief of repression. Repression by CREB requires its binding to the c-jun promoter. In NIH 3T3 cells stably expressing CREB, c-jun is no longer induced by serum, but this repression can be relieved by treatment of the cells with forskolin, an agonist of the adenylate cyclase pathway. Thus, CREB has a dual function, that of a repressor in the absence of phosphorylation and an activator when phosphorylated by protein kinase A.
Lamph, W. W., Dwarki, V. J., Ofir, R., Montminy, M., & Verma, I. M. (1990). Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation. Proceedings of the National Academy of Sciences of the United States of America, 87(11), 4320–4324. https://doi.org/10.1073/pnas.87.11.4320