THE ROLE OF GRK2 S-NITROSYLATION IN CARDIAC HOMEOSTASIS AND HYPERTROPHIC RESPONSE

Abstract

Heart failure is a condition that plagues the Western world, stripping quality of life and imposing excessive financial burdens on its victims, their families, and their medical caretakers. As a response, modern research focuses on identifying the causes, underlying mechanisms, and potential therapeutic strategies for eradicating this disease. Our lab has committed several decades to elucidating the role of G protein-coupled receptor kinase 2 (GRK2) in heart failure. GRK2 is a kinase involved in G-protein coupled receptor internalization and desensitization under HYPERTROPHIC stress. In 2014, our group published a paper identifying a nodal point in GRK2 at Cysteine 340, where GRK2 S-nitrosylation occurs. This established a co-inhibitory relationship between GRK2 and eNOS, reliant on a delicate balance of each molecule to retain basal function without allowing GRK2 to reach pathological levels. My work has focused on further establishing this relationship, identifying mechanistic detail