UMMS Affiliation
Department of Medicine, Division of Cardiovascular Medicine
Publication Date
6-25-2008
Document Type
Article
Subjects
Animals; Antioxidants; COS Cells; Cell Proliferation; Cercopithecus aethiops; Endoplasmic Reticulum; Endothelial Cells; Epidermal Growth Factor; Humans; Mice; Mutation; NADPH Oxidase; Oxidation-Reduction; Phosphorylation; Protein Transport; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Reactive Oxygen Species; Receptor, Epidermal Growth Factor; *Signal Transduction; Substrate Specificity
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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.
DOI of Published Version
10.1083/jcb.200709049
Source
J Cell Biol. 2008 Jun 30;181(7):1129-39. Epub 2008 Jun 23. Link to article on publisher's site
Journal/Book/Conference Title
The Journal of cell biology
Related Resources
PubMed ID
18573911
Repository Citation
Chen, Kai; Kirber, Michael T.; Xiao, Hui; Yang, Yu; and Keaney, John F., "Regulation of ROS signal transduction by NADPH oxidase 4 localization" (2008). Open Access Articles. 1915.
https://escholarship.umassmed.edu/oapubs/1915