| First Author | Schumacher SM | Year | 2016 |
| Journal | Sci Signal | Volume | 9 |
| Issue | 420 | Pages | ra30 |
| PubMed ID | 27016525 | Mgi Jnum | J:259456 |
| Mgi Id | MGI:6141087 | Doi | 10.1126/scisignal.aae0549 |
| Citation | Schumacher SM, et al. (2016) A peptide of the RGS domain of GRK2 binds and inhibits Galpha(q) to suppress pathological cardiac hypertrophy and dysfunction. Sci Signal 9(420):ra30 |
| abstractText | G protein-coupled receptor (GPCR) kinases (GRKs) play a critical role in cardiac function by regulating GPCR activity. GRK2 suppresses GPCR signaling by phosphorylating and desensitizing active GPCRs, and through protein-protein interactions that uncouple GPCRs from their downstream effectors. Several GRK2 interacting partners, including Galpha(q), promote maladaptive cardiac hypertrophy, which leads to heart failure, a leading cause of mortality worldwide. The regulator of G protein signaling (RGS) domain of GRK2 interacts with and inhibits Galpha(q) in vitro. We generated TgbetaARKrgs mice with cardiac-specific expression of the RGS domain of GRK2 and subjected these mice to pressure overload to trigger adaptive changes that lead to heart failure. Unlike their nontransgenic littermate controls, the TgbetaARKrgs mice exhibited less hypertrophy as indicated by reduced left ventricular wall thickness, decreased expression of genes linked to cardiac hypertrophy, and less adverse structural remodeling. The betaARKrgs peptide, but not endogenous GRK2, interacted with Galpha(q) and interfered with signaling through this G protein. These data support the development of GRK2-based therapeutic approaches to prevent hypertrophy and heart failure. |
