| First Author | Islam KN | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 50 | Pages | 35683-9 |
| PubMed ID | 24174526 | Mgi Jnum | J:207205 |
| Mgi Id | MGI:5554659 | Doi | 10.1074/jbc.M113.529347 |
| Citation | Islam KN, et al. (2013) Regulation of nuclear factor kappaB (NF-kappaB) in the nucleus of cardiomyocytes by G protein-coupled receptor kinase 5 (GRK5). J Biol Chem 288(50):35683-9 |
| abstractText | G protein-coupled receptor kinase 5 GRK5 plays a key role in regulating cardiac signaling and its expression is increased in heart failure. GRK5 activity in the nucleus of myocytes has been shown to be detrimental in the setting of pressure-overload hypertrophy. The ubiquitous nuclear transcription factor kappaB (NF-kappaB) is involved in the regulation of numerous genes in various tissues, and activation of NF-kappaB has been shown to be associated with heart disease. Herein, we investigated whether GRK5 can specifically regulate the NF-kappaB signaling pathway in myocytes. We found that overexpression of GRK5 increased the levels of NF-kappaB -p50 and p65 in vitro and in vivo, whereas loss of GRK5 resulted in lower cardiac NF-kappaB levels. Furthermore, increased GRK5 expression induced the phosphorylation status of p65, increased the activity of a NF-kappaB reporter, and increased NF-kappaB DNA binding activity in cultured neonatal rat ventricular myocytes. Importantly, siRNA against GRK5 presented with the opposite results in neonatal rat ventricular myocytes as p65 and p50 were decreased, and there was a loss of NF-kappaB DNA binding activity. The influence of GRK5 on NF-kappaB expression and activity was dependent on its nuclear localization as overexpression of a mutant GRK5 that cannot enter the nucleus was devoid of NF-kappaB activation or DNA binding. Our study demonstrates that a novel pathological consequence of GRK5 up-regulation in the injured and failing heart is the induction of NF-kappaB expression and activity. |
