The ability of Ca2+ /calmodulin-dependent protein kinases (CaMKs) to regulate transcription of the rat prolactin (PRL) gene has been examined. We found that KN-62, a potent inhibitor of CaM kinases, blunted the ability of TRH to activate the prolactin promoter. Transfection experiments using expression plasmids for constitutively active forms of CaMKI, CaMKII, or CaMKIV show that CaMKII is the most effective activator of prolactin promoter expression. Deletion studies demonstrated that the upstream boundary of sequences necessary to respond to CaMKII is located within the distal enhancer of the prolactin gene. Neither the distal enhancer alone nor the proximal region of the prolactin gene are sufficient to mediate a response to CaMKII. Mutational analysis suggests that several Pit-1 binding sites contribute to CaMKII responsiveness. These findings suggest that CaMKII responsiveness of the prolactin promoter requires multiple factor binding sites in both the distal and proximal regions of the gene.
|Original language||English (US)|
|Number of pages||8|
|Journal||Molecular and Cellular Endocrinology|
|State||Published - 1997|
- Protein kinase
ASJC Scopus subject areas
- Molecular Biology