Proteins that stop a major signaling pathway can also generate ne...( DURHAM N.C. Duke University Medical...)

DURHAM, N.C. Duke University Medical Center researchers have recently discovered that a crucial communications pathway in cells not only stops cells from making proteins, it also makes them go. The team was able to define the way in which proteins called beta arrestins (for their role in stopping signals) also turn on pathways that ultimately lead to the production of new proteins in virtually all tissues in the body.

Because proteins are the building blocks for all cells, this new pathway for the general control of protein manufacturing has opened a new universe for biological studies.

The beta arrestins were discovered two decades ago as the off switches for G protein-coupled receptors (GPCRs) on the cell surface, which do the job of sending and receiving important signals for cells. This mechanism is the target of about a third of all pharmaceuticals today.

The GPCRs, which were first theorized and discovered at Duke by the study's senior author, Robert J. Lefokowitz, MD, begin a signaling cascade that transmits a message from the cell surface, such as a hormone or neurotransmitter, to the cell's interior and tells it to do something, such as cranking out a particular protein.

These receptors regulate virtually all physiological processes, everything from heart rate to mood. Research on GPCRs has led to numerous successful drugs, including beta blockers which help relieve hypertension, angina and coronary disease, as well as new antihistamines and ulcer drugs. They also formed the basis of Nobel Prize winning work on smell receptors.

"The reason the new work is so exciting to me is that it reminds us, yet again, how the scientific process continuously renews itself, said Lefkowitz, James B. Duke Professor of Medicine and investigator of the Howard Hughes Medical Institute. "We discovered the beta arrestins almost 20 years ago, and now we find out they play signaling roles we never dreamed of back then. We are hop
'/>"/>