Receptor Activation of NADPH Oxidases

Abstract

Reactive oxygen species (ROS) have been implicated in many intra- and intercellular processes. High levels of ROS are generated as part of the innate immunity in the respiratory burst of phagocytic cells. Low levels of ROS, however, are generated in a highly controlled manner by various cell types to act as second messengers in redox-sensitive pathways. A NADPH oxidase has been initially described as the respiratory burst enzyme in neutrophils. Stimulation of this complex enzyme system requires specific signaling cascades linking it to membrane-receptor activation. Subsequently, a family of NADPH oxidases has been identified in various nonphagocytic cells. They mainly differ in containing one out of seven homologous catalytic core proteins termed NOX1 to NOX5 and DUOX1 or 2. NADPH oxidase activity is controlled by regulatory subunits, including the NOX regulators p47phox and p67phox, their homologs NOXO1 and NOXA1, or the DUOX1 or 2 regulators DUOXA1 and 2. In addition, the GTPase Rac modulates activity of several of these enzymes. Recently, additional proteins have been identified that seem to have a regulatory function on NADPH oxidase activity under certain conditions. We will thus summarize molecular pathways linking activation of different membrane-bound receptors with increased ROS production of NADPH oxidases.

MicroRNA profiling differentiates colorectal cancer according to KRAS status

“…NADPH is an important component of the NADPH oxidase complex; NADPH oxidases play different roles in cell signaling, gene expression regulation, cell death, differentiation, and growth (Sancho and Fabregat, 2011). NADPH oxidases transmit signals to downstream receptor tyrosine kinases, such as EGFR (Petry et al, 2010), and inhibitors of NADPH oxidases reduce EGFR level (Sancho and Fabregat, 2011). In our analysis, NOX4/ NADPH oxidase 4 was a predicted target gene of miR-92a.…”

Transit of H2O2 across the endoplasmic reticulum membrane is not sluggish

“…Here, the binding of extracellular growth factor ligands to receptor tyrosine kinases (RTKs) on the cell surface frequently co-activates members of the NADPH oxidase (Nox) family [8][9][10] protein tyrosine phosphatases (PTPs) on a reactive cysteine in their active site [11,12].…”

The NADPH oxidase inhibitor VAS2870 impairs cell growth and enhances TGF-β-induced apoptosis of liver tumor cells

“…These enzymes are widely expressed in numerous tissues and play different roles including cell signaling, gene expression regulation, cell death, differentiation and growth [3]. Most of NOX functions are related to signal transduction from membrane receptors and, consequently, they are activated in response to extracellular signals, such as cytokines or growth factors [4].…”