Two Nobelists Honored for Protein Receptor Discoveries
Two American investigators who have made key discoveries studying the structure and function of G-protein–coupled receptors in research stretching back to the 1960s share this year’s Nobel Prize in chemistry, awarded earlier today.
Robert J. Lefkowitz, M.D., a professor at Duke University Medical Center and an investigator at the Howard Hughes Medical Institute; and Brian K. Kobilka, M.D., a professor at Stanford University School of Medicine, were selected by the Royal Swedish Academy of Sciences for the SEK 8 million ($1.2 million) award based on their work in discovering the workings of the receptors, through which about half of all medications act.
The research originated in 1968 when Dr. Lefkowitz began attaching an iodine isotope to various hormones, using the radioactivity to trace cells' receptors substances. That work managed to unveil several receptors, among them the β-adrenergic receptor. Dr. Lefkowitz’s team extracted the adrenalin receptor from its hiding place in the cell wall, gaining an initial understanding of how it works.
Nearly two decades later, after Dr. Kobilka joined the research team, he successfully isolated from the human genome the gene responsible for coding the β-adrenergic receptor. When the team analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light, then found a whole family of receptors—the G-protein–coupled receptors—that looked alike and function in the same manner.
About 1,000 genes code for the G-protein–coupled receptors (GPCRs). Some are located in the eyes, tongue, and nose, focusing on specific stimuli that include light, taste, and smell. Others alert cells to the presence of adrenalin, histamine, dopamine and serotonin.
"This ground-breaking work spanning genetics and biochemistry has laid the basis for much of our understanding of modern pharmacology as well as how cells in different parts of living organisms can react differently to external stimulation," Mark Downs, chief executive of Britain's Society of Biology, said in a statement today.
Last year, Dr. Kobilka led a research team in capturing an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell.
An editorial commentary honoring Dr. Lefkowitz for his work was published in the July 5, 2004 edition (Vol. 1, No. 2) of ASSAY and Drug Development Technologies, a journal published by GEN publisher Mary Ann Liebert, Inc. “Much of our current understanding of GPCR receptor signaling stems from research that occurred in Dr. Lefkowitz’s laboratory from 1973 to the present,” according to the editorial, authored by editor-in-chief Jim Inglese, Ph.D., and John R. Raymond, M.D., then-professor of medicine and vp for academic affairs, Medical University of South Carolina, and nowpresident and CEO of The Medical College of Wisconsin.
“The future appears as bright as ever for Dr. Lefkowitz and his colleagues whose efforts continue to advance science and medicine,” the editorial added.