2012 Nobel Prize-Winning Chemistry Research Documented in CAS Databases
On October 10, 2012, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to two scientists “for studies of G-protein-coupled receptors.”
- Dr. Robert J. Lefkowitz, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA
- Dr. Brian K. Kobilka, Stanford University School of Medicine, Stanford, CA, USA
G-protein-coupled receptors (GPCRs) are plasma membrane-spanning proteins that transmit information, in the form of chemical signals, from the outside of a cell to proteins on the inside. For example, when the GPCR β2 adrenergic receptor (βAR) binds epinephrine on the outside of a cell, it activates a GTP-binding protein (G-protein) on the inside. This initial transmission of “information” triggers a cascade of downstream signaling that leads to a variety of physiologic responses from the cell.
In 1970, Robert Lefkowitz published two articles describing the existence of GPCRs, and a decade later, he published a general mechanism of activation. The first high-resolution image of transmembrane signaling by a GPCR was published in 2011 by Lefkowitz’s former post-doc, Brian Kobilka.
Much of the Nobel Prize-winning research of Lefkowitz and Kobilka is represented in the CAS databases, with nearly 1,000 references to their journal articles since 1970. Examples of their most important published research include:
- Lefkowitz, R.J.; Roth, J.; Pricer, W.; Pastan, I. ACTH receptors in the adrenal: specific binding of ACTH-125I and its relation to adenylyl cyclase. Proc. Natl. Acad. Sci. USA 1970, 65, 745-752. [see it in SciFinder]
- Lefkowitz, R.J.; Roth, J.; Pastan, I. Radioreceptor assay for adrenocorticotropic hormone: new approach to assay of polypeptide hormones in plasma. Science 1970, 170, 633-635. [see it in SciFinder]
- De Lean, A.; Stadel, J.M.; Lefkowitz, R.J. A ternary complex model explains the agonistspecific binding properties and the adenylate cyclase-coupled beta-adrenergic receptor. J. Biol. Chem. 1980, 255, 7108-7117. [see it in SciFinder]
- Rasmussen, S.G.; DeVree, B.T.; Zou, Y.; Kruse, A.C.; Chung, K.Y.; Kobilka, T.S.; Thian, F.S.; Chae, P.S.; Pardon, E.; Calinski, D.; Mathiesen, J.M.; Shah, S.T.; Lyons, J.A.; Caffrey, M.; Gellman, S.H.; Steyaert, J.; Skiniotis, G.; Weis, W.I.; Sunahara, R.K.; Kobilka, B.K. (2011) Crystal structure of the β2 adrenergic receptor–Gs protein complex. Nature 2011, 477, 549-555. [see it in SciFinder]
CAS congratulates the 2012 Nobel Laureates in Chemistry for their important contributions to science!