NADPH oxidase activation in neutrophils: Role of the phosphorylation of its subunits

• Published in: European journal of clinical investigation Vol. 48; no. S2; pp. e12951 - n/a
• Main Authors: Belambri, Sahra A., Rolas, Loïc, Raad, Houssam, Hurtado‐Nedelec, Margarita, Dang, Pham My‐Chan, El‐Benna, Jamel
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-11-2018; Wiley
• Subjects: Bacterial Proteins - pharmacokinetics; Catalysis; Cell activation; CYBB protein; Cytochrome; Cytochrome b558; Cytochromes; Enzyme Activation - physiology; Enzyme Activators - pharmacology; Enzymes; gp91phox; Guanosine diphosphate; Guanosine triphosphate; Humans; Immunity; Immunology; Inflammatory diseases; Innate immunity; Leukocytes (neutrophilic); Life Sciences; Membrane proteins; Microorganisms; NAD(P)H oxidase; NADPH oxidase; NADPH Oxidase 2 - metabolism; NADPH Oxidases - metabolism; Neutrophils; Neutrophils - enzymology; NOX2; Oxidase; p22phox; p47phox; p67phox and p40phox; Phospholipids; Phosphoproteins - metabolism; Phosphorylation; Phosphorylation - physiology; protein phosphorylation; Proteins; Protons; Rac2; Rac2 protein; Reactive oxygen species; Superoxide; Tetradecanoylphorbol Acetate - pharmacokinetics; p22phox; p47phox; p67phox and p40phox; NADPH oxidase; Rac2; protein phosphorylation; gp91phox; neutrophils; NOX2
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.12951

Neutrophils are key cells of innate immunity and during inflammation. Upon activation, they produce large amounts of superoxide anion (O2−.) and ensuing reactive oxygen species (ROS) to kill phagocytized microbes. The enzyme responsible for O2−. production is called the phagocyte NADPH oxidase. This is a multicomponent enzyme system that becomes active after assembly of four cytosolic proteins (p47phox, p67phox, p40phox and Rac2) with the transmembrane proteins (p22phox and gp91phox, which form the cytochrome b558). gp91phox represents the catalytic subunit of the NADPH oxidase and is also called NOX2. NADPH oxidase‐derived ROS are essential for microbial killing and innate immunity; however, excessive ROS production induces tissue injury and prolonged inflammatory reactions that contribute to inflammatory diseases. Thus, NADPH oxidase activation must be tightly regulated in time and space to limit ROS production. NADPH oxidase activation is regulated by several processes such as phosphorylation of its components, exchange of GDP/GTP on Rac2 and binding of p47phox and p40phox to phospholipids. This review aims to provide new insights into the role of the phosphorylation of the NADPH oxidase components, that is gp91phox, p22phox, p47phox, p67phox and p40phox, in the activation of this enzyme.