Congratulations to Jeff Benovic, PhD, Thomas Eakins Endowed Professor of Biochemistry & Molecular Biology at Thomas Jefferson University, who was recently honored with the “Discovery of the Year Award for Basic Science” at the 2018 Sidney Kimmel Cancer Center at Jefferson Health (SKCC) Member Retreat, held at Citizens Bank Park in Philadelphia. The award was presented to Benovic by Andrew Aplin, PhD, Associate Director of Basic Research at the SKCC.
Benovic, who is also Associate Director of Education at the SKCC, received the award because of the research that he and his laboratory have been conducting on the mechanisms that regulate G protein-coupled receptor (GPCR) signaling, with a particular focus on the role of GPCR kinases (GRKs) and arrestins.
GRKs play a central role in regulating GPCR function by switching cells from G protein signaling to arrestin-mediated signaling. In recent work published in the scientific journal Cell, the group studied the interaction of GRK5 with the b2-adrenergic receptor (b2AR), a GPCR that is activated by catecholamines. Their findings reveal key mechanistic features of how these two proteins interact and how this interaction leads to conformational changes in the GRK that are essential for mediating receptor phosphorylation.
Moreover, the molecular model derived from these studies provides important insights into a common mechanism of GRK-GPCR interaction, raising the exciting possibility of exploiting this mechanism to control GPCR signaling.
The new findings hold promise for many clinical applications in the future. GPCRs are the target of about 30% of drugs currently on the market, including drugs for the treatment of cancer, cardiovascular and airway disease, as well as various neurological and metabolic disorders. “Because GRKs play a central role in regulating GPCR function, a better understanding of the mechanisms involved in this process provides an opportunity to manipulate this pathway in treating various diseases,” Benovic said.