6533b86ffe1ef96bd12ce783

RESEARCH PRODUCT

Mitochondrial G protein coupled receptor kinase 2 regulates proinflammatory responses in macrophages.

Bruno TrimarcoAnna Lisa CarilloMichele CiccarelliA. RungiAlfredo FuscoGerald W. DornGuido IaccarinoAntonio AnastasioD. Sorriento

subject

LipopolysaccharidesG-Protein-Coupled Receptor Kinase 2BiophysicsβARK-ctGRK2InflammationMitochondrionBiochemistryArticleProinflammatory cytokineMiceStructural BiologyGeneticsmedicineAnimalsHumansReceptorMolecular BiologyInflammationG protein-coupled receptor kinasebiologyKinaseSubcellular localizationBeta adrenergic receptor kinaseMacrophagesCell BiologySubcellular localizationCell biologyMitochondriabiology.proteinmedicine.symptomReactive Oxygen SpeciesSignal Transduction

description

G-protein-coupled receptor kinase 2 (GRK2) levels are elevated in inflammation but its role is not clear yet. Here we show that GRK2 expression is dependent on NFκB transcriptional activity. In macrophages, LPS induces GRK2 accumulation in mitochondria increasing biogenesis. The overexpression of the carboxy-terminal domain of GRK2 (βARK-ct), known to displace GRK2 from plasma membranes, in macrophages induces earlier localization of GRK2 in mitochondria in response to LPS leading to increased mt-DNA transcription, reduced ROS production and cytokines expression. Our study shows the relevance of GRK2 subcellular localization in macrophage’s biology and its potential therapeutic properties in inflammation.

yearjournalcountryeditionlanguage
2013-09-10
10.1016/j.febslet.2013.09.002http://hdl.handle.net/11386/4144054