My research interest is the regulation and function of second messenger systems in mammalian cells. These membrane systems comprised of receptors, coupling proteins (GTP binding proteins) and effectors (adenylate cyclase, phospholipase C) transduce various chemical (neurotransmitters and hormone) and physical (light) signals received by cells into intracellular messengers such as cyclic AMP, CA++, inositol phosphates, and diacylglycerides. The responsiveness of the second messenger systems to hormones and neurotransmitters is dramatically regulated by a variety of mechanisms: protein kinases, internalization, down regulation, and RGS proteins (GTPase stimulating proteins). These mechanisms allow the cell to adapt to many types of signaling mechanisms, and they are intimately involved in many cellular processes; for example, muscle tone in lung tissue, learning and memory and the control of cell growth. The goals of my laboratory are to understand the mechanisms of desensitization of the G-protein coupled receptors and we are currently investigating the roles of protein kinases (PKA, GRKs & PKC) and phosphatases in the regulation of adrenaline (epinephrine) stimulation of adenylate cyclase. Our primary approach merges genetics (the use of mutants of the beta-adrenergic receptor) with biochemistry (receptor phosphorylation, receptor function, ligand binding) and pharmacology (analysis of the effects of strong and weak agonists and antagonists).
Publications/Creative Works
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