Cyclic Nucleotide Signaling Pathways
We are studying the mechanisms that cells use to regulate metabolism and cell function in response to physiological stimuli such as hormones, neurotransmitters, and other signals. These agents work by eliciting changes in the levels of specific intracellular molecules known as second messengers, and these second messengers interact with cellular proteins to bring about changes in carbohydrate and fat metabolism, cardiovascular function, gene expression, and myriad other processes. Cyclic nucleotides, cyclic AMP and cyclic GMP, are important second messengers that are involved in all these processes, and these nucleotides bind to specific intracellular protein receptors which then bring about the changes in cellular function.
In particular, we study two families of intracellular receptors for cyclic nucleotides, cyclic nucleotide-dependent protein kinases and cyclic nucleotide phosphodiesterases. These proteins are present in all mammalian cells and play central roles in integrating the regulation of cellular metabolism. We are interested in determining how these protein families function in the cell to modulate the tissues? physiological responses, how their functions relate to one another, and how these processes are altered in pathological states such as hypertension, asthma, diabetes, and male impotence. We also study these proteins at the molecular level using both purified proteins, as well as proteins that have been modified using site-directed mutagenesis, in order to determine the mechanisms that are critical to determining protein function.