Gene expression and cAMP.

Abstract

By comparing the 5''-flanking region of the porcine gene for the urokinase form of plasminogen activator with those of other cAMP-regulated genes, a 29-nucleotide sequence was identified that is tentatively proposed as the cAMP-regulatory unit. Homologous sequences are present in the cAMP-regulated rat tyrosine aminotransferase, prolactin and phosphoenolpyruvate carboxykinase genes and 5'' to the transcription initiation sites of cAMP-regulated Escherichia coli genes. The expression of cAMP-responsive genes in higher eukaryoytes may be controlled, as in E. coli, by proteins that form complexes with cAMP and then show sequence-specific DNA-binding properties. The complex formed by cAMP and the regulatory subunit of the type II mammalian protein kinase might be 1 candidate for this function. This subunit may have retained both the DNA-binding specificity and transcription-regulating properties in addition to the nucleotide-binding domains of the bacterial cAMP-binding protein. If this were so, dissociation of protein kinase by cAMP would activate 2 processes: protein phosphorylation by the catalytic subunit and transcription regulation by the regulatory subunit.