Abstract: |
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. © 2005 by The National Academy of Sciences of the USA. |
Keywords: |
signal transduction; epidermal growth factor; controlled study; human cell; mutation; models, biological; epidermal growth factor receptor; cell line; receptor, epidermal growth factor; enzyme activity; transfection; recombinant proteins; reactive oxygen species; reactive oxygen metabolite; ligands; base sequence; hydrogen peroxide; protein subunits; cell communication; extracellular fluid; ligand binding; receptor binding; erythropoietin receptor; dna, complementary; receptors, cell surface; kinase; granulocyte-macrophage colony-stimulating factor; catalase; granulocyte macrophage colony stimulating factor receptor; receptors, granulocyte-macrophage colony-stimulating factor; cytokine hematopoietin; peroxidases
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