JCB logo
Sign up for e-mail content alerts
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online June 23, 2008
doi:10.1083/jcb.200709049
The Journal of Cell Biology, Vol. 181, No. 7, 1129-1139
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Chen et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Chen, K.
Right arrow Articles by Keaney, J. F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, K.
Right arrow Articles by Keaney, J. F., Jr.
Related Collections
Right arrowRelated In this Issue article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Regulation of ROS signal transduction by NADPH oxidase 4 localization

Kai Chen, Michael T. Kirber, Hui Xiao, Yu Yang, and John F. Keaney, Jr.

Division of Cardiovascular Medicine, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605

Correspondence to Kai Chen: kai.chen{at}umassmed.edu

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.

Abbreviations used in this paper: EGFR, EGF receptor; ERK, extracellular signal-regulated kinase; HAEC, human aortic endothelial cell; MEF, mouse embryonic fibroblast; MSP, mitochondrial signal peptide; NO, nitric oxide; NOS, NO synthase; Nox, NADPH oxidase; PTP, protein tyrosine phosphatase; ROS, reactive oxygen species; VE, vascular endothelial.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related In this Issue article

How cells make local calls
Mitch Leslie
J. Cell Biol. 2008 181: 1043. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents