Congratulations to Dr. Bob Lefkowitz and Dr. Brian Kobilka!

[caption id="attachment_611" align="alignleft" width="664" caption="This year's winners of the Chemistry Nobel: Robert Lefkowitz (left) and Brian Kobilka. (Image courtesy of nobelprize.org)"][/caption] The JCI would like to congratulate Dr. Bob Lefkowitz and Dr. Brian Kobilka on winning the 2012 Nobel Prize in Chemistry for studies of G-protein coupled receptors (GPCRs). Dr. Lefkowitz, an investigator at the Howard Hughes Medical Institute and Duke University Medical Center, is also the Chair of the JCI Executive Board. GPCRs, also known as seven-transmembrane domain receptors, are cell surface proteins that sense molecules outside the cell and activate signal transduction pathways that allow cells to respond to their environment. The receptors are activated by a variety of stimuli including light, odors, hormones, neurotransmitters, and drug compounds. In fact, over 50% of pharmaceuticals act either directly or indirectly through GPCRs. For many years, scientist were aware that cells were capable of sensing and responding to environmental stimuli, but the actual cellular mechanisms that mediated this process were unknown. In 1968, Lefkowitz began tracing radiolabeled hormone binding in cells and discovered a GPCR embedded in the cell surface that bound the hormone adrenaline. Lefkowitz was able to purify this receptor and determine how it works. Brian Kobilka joined the Lefkowitz lab in 1984. He isolated the gene that codes for the b-adrenergic receptor and determined that it was highly similar to the receptor that senses light, the rhodopsin receptor, which was also known to activate a G-protein. The fact that these two receptors, which were turned on by such different stimuli, were so highly similar was shocking. This discovery led to the identification of an entire family of GPCRs, which now consists of over 800 different receptors. Over the past 30 years, both Lefkowitz and Kobilka have continued to enhance our understanding of GPCRs. Lefkowitz has identified novel GPCR signaling mechanisms that do not involve the G-protein, while Kobilka has elucidated the structure of GPCRs interacting with ligands and G-proteins that have changed our understanding of the mechanics of GPCR signaling. These findings will surely lead to an even greater understanding of cell physiology and provide critical information for the development of new therapeutics that target these proteins.