Fusion of G Protein-Coupled Receptors to the Human Transducerome (2016)
Undergraduates: Ariana Gavin, Justin G. English, Ryan T. Strachan, John McCorvy
Faculty Advisor: Bryan Roth
Department: Biology
G protein-coupled receptors (GPCRs) are fundamental transmembrane proteins that facilitate the majority of physiological processes in humans. They bind various endogenous and exogenous ligands, which leads to activation of intracellular signal transduction proteins. However, it has been found that agonists activate these transduction pathways disproportionately, a phenomenon termed "biased agonism". GPCRs are major targets of FDA-approved drugs due to their central involvement in human disease, and therefore it is of interest to understand the nature of biased agonism in
order to improve therapeutic efficacy and reduce drug side effects. Currently, little is known about agonist signaling across the entirety of the human transducerome. We hypothesize that the production of signaling profiles for receptor-transducer pairs will give insight into biased agonism that may be utilized for therapeutic advancement. We will determine these profiles in vitro by fusing two clinically relevant GPCRs (D2R and 5HT2A) to the human transducerome.