Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling
Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling
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DOI：
10.1073/pnas.0501154102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Golde, DW
中科院分区：
文献类型：
--
作者：
DeYulia, GJ;Cárcamo, JM;Golde, DW
活性氧（ROS）是受体后细胞内信号通路的关键成分；然而，ROS在信号起始中的作用尚不确定。我们发现受体-配体相互作用导致过氧化氢（H2O2）的产生。利用造血素受体超家族的成员，以及EGF受体，我们发现H2O2是由细胞和无细胞系统中特异性受体-配体相互作用产生的。有了同源配体，受体的胞外结构域足以产生H2O2。我们还发现，在不能结合配体的粒细胞-巨噬细胞集落刺激因子受体突变体中，H2O2的产生减少。在没有配体的情况下，外源添加H2O2诱导信号转导，而过氧化氢酶和膜结合的过氧化物氧还蛋白抑制配体依赖性信号转导。我们的研究结果表明，受体-配体相互作用产生的H2O2作为一种化学介质参与促进细胞信号传导。
Reactive oxygen species (ROS) are key components of postreceptor intracellular signaling pathways; however, the role of ROS in signal initiation is uncertain. We discovered that receptor-ligand interaction caused the generation of hydrogen peroxide (H2O2). Using members of the hematopoietin receptor superfamily, as well as EGF receptor, we show that H2O2 is generated by specific receptor-ligand interaction in cells and in cell-free systems. With cognate ligand, the extracellular domain of the receptor was sufficient for H2O2 generation. We also found that production of H2O2 was diminished in a granulocyte-macrophage colony-stimulating factor receptor mutant unable to bind ligand. Exogenously added H2O2 induced signaling in the absence of ligand, whereas catalase and a membrane-bound peroxiredoxin inhibited ligand-dependent signaling. Our results suggest that H2O2 produced by receptor-ligand interaction is involved as a chemical mediator that facilitates cell signaling.