Regulation of β-Adrenergic Receptor Signaling by S-Nitrosylation of G-Protein-Coupled Receptor Kinase 2

摘要: β-adrenergic receptors (β-ARs), prototypic G-protein-coupled (GPCRs), play a critical role in regulating numerous physiological processes. The GPCR kinases (GRKs) curtail G-protein signaling and target for internalization. Nitric oxide (NO) and/or S-nitrosothiols (SNOs) can prevent the loss of β-AR vivo, but molecular details are unknown. Here we show mice that SNOs increase expression agonist-stimulated receptor downregulation; cells, decrease GRK2-mediated phosphorylation subsequent recruitment β-arrestin to receptor, resulting attenuation desensitization In both cells tissues, GRK2 is S-nitrosylated by as well NO synthases, S-nitrosylation increases following stimulation multiple GPCRs with agonists. Cys340 identified principal locus inhibition S-nitrosylation. Our studies thus reveal central mechanism through which regulated.