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.

Rights and Permissions

Citation: J Cell Biol. 2008 Jun 30;181(7):1129-39. Epub 2008 Jun 23. Link to article on publisher's site

DOI of Published Version

10.1083/jcb.200709049

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of cell biology

PubMed ID

18573911

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.