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

ABSTRACT: 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 NF?B transcriptional activity. In macrophages, LPS induces GRK2 accumulation in mitochondria increasing biogenesis. The overexpression of the carboxy-terminal domain of GRK2 (?ARK-ct), known to displace GRK2 from plasma membranes, induces earlier localization of GRK2 to mitochondria in response to LPS leading to increased mt-DNA transcription and reduced ROS production and cytokine expression. Our study shows the relevance of GRK2 subcellular localization in macrophage biology and its potential therapeutic properties in inflammation.

SUBMITTER: Sorriento D

PROVIDER: S-EPMC4260621 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Sorriento D D Fusco A A Ciccarelli M M Rungi A A Anastasio A A Carillo A A Dorn G W GW Trimarco B B Iaccarino G G

FEBS letters 20130910 21

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, induces earlier localization of GRK2 to mitochondria in response to LPS leading to increased mt-DNA transcrip ...[more]

PMID: 24036448

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