ABSTRACT
The activity of receptors and ion channels influences gene and protein expression in neurons. Second messengers (calcium, cyclic AMP) regulate the activity of protein kinases (proteins that transfer phosphate groups to a substrate protein) and phosphatases (proteins that remove phosphate groups from a substrate protein). In all cases studied to date, the activation of neurotransmitter receptors changes the state of phosphorylation of
neuronal proteins. One group of proteins regulated by phosphorylation are the transcription factors that operate by recruiting the transcription initiation complex and RNA polymerase to particular genes. Among the best-studied transcription factors in the brain is the Ca2+ and cyclic AMP-responsive element binding protein (CREB) (Montminy et al., 1990). The study of CREB has provided us with an insight into the complex consequences of transcription factor activation and gene expression on higher brain function. Activated by phosphorylation, CREB regulates the expression of several target genes (e.g., genes for peptide neurotransmitters, enzymes involved in neurotransmitter synthesis, and growth factors). The discovery that CREB plays a pivotal role in processes such as learning and memory provided a link between gene regulation and cognitive function (Frank & Greenberg, 1994; Stevens, 1994).
