1988 Krebs Lecture
1988 Edwin G. Krebs Lectureship in Molecular Pharmacology
The First Annual Edwin G. Krebs Lecture in Molecular Pharmacology
The Adrenergic Receptors
Robert J. Lefkowitz, Ph.D.
Professor, Departments of Medicine and Biochemistry
Investigator, Howard Hughes Medical Institute, Duke University
Wednesday, April 6, 1988
1:30 PM, Room T-625 HSC
Dr. Lefkowitz is a leading investigator of the structure and mechanism of action of hormone receptors that regulate intracellular levels of cyclic AMP and other second messengers. Dr. Lefkowitz's research has focused on the receptors for epinephrine and norepinephrine, which play critical roles in regulating carbohydrate metabolism in liver and muscle, heart rate and contractile force, blood pressure, and neuronal function. Dr. Lefkowitz and his colleagues have identified and purified the protein components of the alpha- and beta-adrenergic receptors and restored the function of the beta-adrenergic receptor in purified form by reconstitution with guanyl nucleotide regulatory proteins and the catalytic subunit of adenylate cyclase in phospholipid vesicles, cloned the genes for these receptor proteins, and determined their primary structure. These studies have laid the foundation for study of the structure and function of these proteins in more detail by mutation and expression of cloned cDNA. Dr. Lefkowitz's investigations also have identified a new protein kinase that is specific for the agonist-occupied forms of the adrenergic receptors and reduces their activity by phosphorylation. This new kinase is considered to play a major role in desensitization of cells to the continued presence of adrenergic hormones and perhaps to other cellular regulators. Dr. Lefkowitz's work exemplifies the goal of research in molecular pharmacology to provide understanding of the molecular basis of the actions of hormones and drugs.
Dr. Lefkowitz received an M.D. degree from Columbia University College of Physicians and Surgeons and was a clinical and research fellow at the National Institutes of Health and at Massachusetts General Hospital before taking a position as associate professor of medicine at Duke University Medical Center in 1973. He is a member of several editorial boards, including the Journal of Biological Chemistry, Molecular Pharmacology, and the Journal of Clinical Investigation. His research contributions have been recognized by his selection for numerous distinguished lectureships and awards, including the John J. Abel and the Goodman and Gilman Awards of the American Society for Pharmacology and Experimental Therapeutics.