Hormonal control of gene expression: multiplicity and versatility of cyclic adenosine 3',5'-monophosphate-responsive nuclear regulators.

A central goal of modern biology is to obtain insights into the molecular mechanisms by which extracellular stimuli modulate the expression of specific genes in a temporal and/or tissue-specific manner. These mechanisms are central to processes such as cellular growth, differentiation, and response to environmental changes. This review focuses on the mechanisms that underlie CAMP-induced changes in gene expression. The CAMP-signalling pathway is one of the major intracellular signal transduction pathways operating in eukaryotic cells (1, 2). The intracellular concentration of CAMP is increased upon stimulation of the adenylyl cyclases. This results in activation of the catalytic subunit of protein kinase-A (PKA), which, in turn, phosphorylates a number of substrates (2). Several genes have been found to be inducible upon an increase in intracellular CAMP concentrations (2, 4). In some cases, activation of specific G-protein-coupled receptors by the respective ligands has been shown to result in either stimulation or repression of CAMP-induced gene expression (4). The identification of CAMP response elements (CREs) in the promoters of several CAMP-inducible genes provided the first link between activation of PKA and CAMP-induced gene expression (5-7; see Ref. 4 for a review). Subsequently, it was shown that specific nuclear factors bind to the various CREs. These proteins were of heterogeneous size and characteristics, suggesting the presence of a family (8). The identification and cloning of the gene encoding for