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PMID: 15795385 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 14 ·2005-04-05 ·Pages 5044-9

DeYulia GJ, Cárcamo JM, Bórquez-Ojeda O, Shelton CC, Golde DW

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.

MeSH Terms
Base Sequence Catalase/pharmacology Cell Line DNA, Complementary/genetics Epidermal Growth Factor/pharmacology ErbB Receptors/metabolism Extracellular Fluid/metabolism Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology Humans Hydrogen Peroxide/metabolism In Vitro Techniques Ligands Models, Biological Mutation Peroxidases/genetics,metabolism Peroxiredoxins Protein Subunits Reactive Oxygen Species/metabolism Receptors, Cell Surface/metabolism Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/chemistry,genetics,metabolism Recombinant Proteins/chemistry,genetics,metabolism Signal Transduction/physiology Transfection
Chemicals
DNA, Complementary Ligands Protein Subunits Reactive Oxygen Species Receptors, Cell Surface Receptors, Granulocyte-Macrophage Colony-Stimulating Factor Recombinant Proteins Epidermal Growth Factor Granulocyte-Macrophage Colony-Stimulating Factor Hydrogen Peroxide Peroxidases Peroxiredoxins Catalase ErbB Receptors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
DeYulia Garrett J
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021, USA.
Cárcamo Juan M
Bórquez-Ojeda Oriana
Shelton Christopher C
Golde David W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0501154102
Published
2005-04-05
Epub
2005-00-28
Pages
5044-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC556007
Subset
IM
Grants
NCI NIH HHS · R01 CA030388 · United States
NCI NIH HHS · CA30388 · United States
External Links
PubMed source DOI: 10.1073/pnas.0501154102 PMC Full Text View journal details
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