G protein-coupled receptors (GPCRs) and their downstream signaling pathways are important for the regulation of many essential cellular processes and are targets of some of the most commonly prescribed drugs, such as those used to treat pain, heart failure, and high blood pressure (e.g. morphine, ? blockers, and angiotensin inhibitors, respectively). GPCR kinases (GRKs) and arrestins work together to regulate GPCR signaling by reducing the ability of receptors to couple with G proteins and by targeting active GPCRs for endocytosis. Although these desensitization mechanisms are important for returning cells to their physiological resting states, GRKs and arrestins are also thought to play prominent roles in addiction and cardiovascular disease, at least in part by instigating other, non-canonical signaling cascades. This proposal seeks funding for a forum that would bring together world-leading researchers who study different aspects of GRK and arrestin biology and their roles in disease called G Protein-Coupled Receptor Kinases and Arrestins: From Structure to Disease. Two major highlights of the meeting will be keynote lectures by 2012 Nobel laureates who are experts in GPCR, GRK, and arrestin structure, function, and cell biology. The meeting is expected to not only stimulate the generation of new hypotheses, collaborations, and methodologies that can be used to study and combat drug abuse and cardiovascular disease, but also provide career advancement and speaking opportunities for junior investigators and underrepresented groups of scientists.
G protein-coupled receptors (GPCRs) control many key aspects of cell physiology and human behavior and are the target of a large fraction of pharmaceutical and illegal drugs. These cell-surface receptors are regulated by two families of proteins known as GPCR kinases (GRKs) and arrestins. Although these proteins provide a key adaptive response in cells, they also are known to play central roles in drug addiction and heart failure. We hypothesize that a meeting that brings together world leaders who study GRKs and arrestins will accelerate the development of new hypotheses, collaborations, and methodologies that can be used to study and combat mechanisms underlying drug abuse and cardiovascular disease.
