Dipartimento di Scienze Biomediche Avanzate, Università Federico II, Napoli, Italy.
FEBS Lett. 2013 Nov 1;587(21):3487-94. doi: 10.1016/j.febslet.2013.09.002. Epub 2013 Sep 10.
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 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.
G 蛋白偶联受体激酶 2（GRK2）的水平在炎症中升高，但它的作用尚不清楚。在这里，我们表明 GRK2 的表达依赖于 NFκB 的转录活性。在巨噬细胞中，LPS 诱导 GRK2 在线粒体中的积累，从而增加生物发生。GRK2 的羧基末端结构域（βARK-ct）的过表达，已知可以将 GRK2 从质膜上置换下来，当 LPS 诱导时，βARK-ct 会导致 GRK2 更早地定位于线粒体，从而增加 mt-DNA 转录，减少 ROS 产生和细胞因子表达。我们的研究表明了 GRK2 亚细胞定位在巨噬细胞生物学中的相关性及其在炎症中的潜在治疗特性。
