This morning the Nobel committee awarded the Prize for Chemistry to two researchers instrumental in the discovery what appears to be the largest class of cell receptors--G-protein coupled receptors (GPCRs).
GPCRs are chemicals on the surface of cells whose primary role is to tell the cell what's happening around it and prompt it to respond appropriately. For example, it is GPCRs that trigger cells to send an neural signal to the brain in response to light, to change metabolism in response to adrenalin, and to transmit a nerve impulse in response to dopamine. The receptors for taste, smell, hormones, and light are all GPCRs. The research of the Nobel Prize recipients, Drs. Robert J. Lefkowitz and Brian K. Kobilka was instrumental in identifying this class of receptors and working out how they function.
As a researcher associated at the NIH in 1968, Dr. Lefkowitz began using radioactively labeled chemicals to trace receptors. In 1975 his group was the first to isolate and chemically characterize one of these receptors, in this case, it was the beta-adrenergic receptor‐one of the types that senses adrenalin.
In the 1980s, Brian Kobilka joined Dr. Lefkowitz's group and began a search for the beta-adrenergic receptor gene--the DNA that provided the code to make the beta-adrenergic receptor protein. He succeeded and published the result in 1986.
In analyzing the genetic sequence of the beta-adrenergic receptor, the research group found it was similar to rhodopsin, which is the receptor for light in the eyes. That comparison suggested that many of the receptors had similar structures and a standard way of functioning. Almost 800 GPCRs have now been characterized.
While the contribution to understanding how cells sense and respond to external signals was tremendous, the discovery of GPCRs has been a major contribution to medicine too. GPCRs make excellent drug targets. If you want to stop a pain signal, produce a hormone to make you sleepy, prevent cells from making a certain chemical like cholesterol, there is a good chance you can find a GPCR that controls the response. Over a third of all drug targets are GPCRs and pharmaceutical companies spend millions screening chemicals to find new interactions with the hundreds of known GPCRs.
For more information on GPCRs utility as drug targets, read High Throughput Drug Discovery with GPCRs.
Comments
If you want to learn more about what they won the prize for, there’s a iBook in iTunes about about how cells respond to stimuli, it’s pretty cool (lots of animations and 3D models of receptors and molecules that you can rotate with your finger). It’s called “Cell Signaling” and it’s in the science and nature section of textbooks.
Hi Mr. Diehl – I think the article may have forgotten to mention that Dr. Lefkowitz has been working at Duke University for the past few decades.