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Updated: Aug 18, 2026

Visualization of Vascular Ca2+ Signaling Triggered by Paracrine Derived ROS
Published on: December 21, 2011
Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling
Garrett J DeYulia1, Juan M Cárcamo, Oriana Bórquez-Ojeda
1Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA.
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.
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