Regulation of ROS signal transduction by NADPH oxidase 4 localization

We demonstrate that nicotinamide adenine dinucleotide phosphate reduced oxidase 4, a major NADPH oxidase isoform expressed in nonphagocytic cells, including vascular endothelium, is localized to the endoplasmic reticulum

Kai Chen; Michael T. Kirber; Hui Xiao; Yu Yang; John F. Keaney

2008

Scholarcy highlights

  • There is considerable evidence indicating that reactive oxygen species are involved in signal transduction
  • The localization of EGF receptor visualized by using an enhanced GFP-EGFR expression vector was consistent with EGFR mobilization to the endoplasmic reticulum induced by PTP1B(D181A/ Q262A) as a result of substrate trapping, which was reversed by nicotinamide adenine dinucleotide phosphate reduced oxidase 4 overexpression
  • The principal finding of this study is that endothelial Nox4, an endogenous source of ROS in human aortic endothelial cells, is localized to the ER and appears involved in the regulation of another ER-residing protein, PTP1B, in a spatially dependent manner
  • We found that cytosolic PTP1B prevented its oxidation by Nox4
  • We found that Nox4-mediated PTP1B oxidation was relevant to epidermal growth factor signaling and was associated with reduced dephosphorylation of EGFR in proximity to the ER
  • These data provide a paradigm for Nox4-dependent redox signaling that highlights spatial specificity within the cell
  • We found that nicotinamide adenine dinucleotide phosphate reduced oxidase 4-mediated PTP1B oxidation was relevant to epidermal growth factor signaling and was associated with reduced dephosphorylation of EGF receptor in proximity to the endoplasmic reticulum

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