Regulation of ROS signal transduction by NADPH oxidase 4 localization

Reactive oxygen species (ROS) function as intracellular signaling molecules in a diverse range of biological processes. However, it is unclear how freely diffusible ROS dictate specific cellular responses. In this study, we demonstrate that nicotinamide adenine dinucleotide phosphate reduced oxidase...

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Bibliographic Details
Published in:The Journal of cell biology Vol. 181; no. 7; p. 1129
Main Authors: Chen, Kai, Kirber, Michael T, Xiao, Hui, Yang, Yu, Keaney, Jr, John F
Format: Journal Article
Language:English
Published: United States 30.06.2008
Subjects:
Animals
Antioxidants - pharmacology
Cell Proliferation - drug effects
Chlorocebus aethiops
COS Cells
Endoplasmic Reticulum - drug effects
Endoplasmic Reticulum - enzymology
Endothelial Cells - cytology
Endothelial Cells - drug effects
Endothelial Cells - enzymology
Epidermal Growth Factor - pharmacology
ErbB Receptors - metabolism
Humans
Mice
Mutation - genetics
NADPH Oxidase 4
NADPH Oxidases - metabolism
Oxidation-Reduction - drug effects
Phosphorylation - drug effects
Protein Transport - drug effects
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism
Reactive Oxygen Species - metabolism
Signal Transduction - drug effects
Substrate Specificity - drug effects
ISSN:1540-8140, 1540-8140
Online Access:Get more information
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Summary:Reactive oxygen species (ROS) function as intracellular signaling molecules in a diverse range of biological processes. However, it is unclear how freely diffusible ROS dictate specific cellular responses. In this study, we demonstrate that nicotinamide adenine dinucleotide phosphate reduced oxidase 4 (Nox4), a major Nox isoform expressed in nonphagocytic cells, including vascular endothelium, is localized to the endoplasmic reticulum (ER). ER localization of Nox4 is critical for the regulation of protein tyrosine phosphatase (PTP) 1B, also an ER resident, through redox-mediated signaling. Nox4-mediated oxidation and inactivation of PTP1B in the ER serves as a regulatory switch for epidermal growth factor (EGF) receptor trafficking and specifically acts to terminate EGF signaling. Consistent with this notion, PTP1B oxidation could also be modulated by ER targeting of antioxidant enzymes but not their untargeted counterparts. These data indicate that the specificity of intracellular ROS-mediated signal transduction may be modulated by the localization of Nox isoforms within specific subcellular compartments.
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ISSN:1540-8140
1540-8140
DOI:10.1083/jcb.200709049