Production of phagocyte oxygen radicals by NOX2 complex bound to RAC2:GTP

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R-HSA-5668629
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Reaction [transition]
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Homo sapiens
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RAC2:GTP-bound NOX2 complex, consisting of CYBB (NOX2), CYBA (p22phox), NCF1 (p47phox), NCF2 (p67phox) and NCF4 (p40phox), acts as an NADPH oxidase to produce superoxide anion O2- in phagosomes of neutorphils, enabling microbicidal activity of neutrophils (Knaus et al. 1991, Kim et al. 2001, Kao et al. 2008, Anderson et al. 2010, Jyoti et al. 2014). Rac2 knockout mice have dramatically reduced NADPH oxidase activity (Roberts et al. 1999). Phosphorylation of NOX2 complex components NCF1 (el Benna et al. 1994), NCF2 (Zhao et al. 2005) and NCF4 (Bouin et al. 1998) contributes to the activation of the phagosomal NADPH oxidase.

Literature References
PubMed ID Title Journal Year
11145705 Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways

Kim, C, Dinauer, MC

J. Immunol. 2001
10072071 Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense

Roberts, AW, Kim, C, Zhen, L, Lowe, JB, Kapur, R, Petryniak, B, Spaetti, A, Pollock, JD, Borneo, JB, Bradford, GB, Atkinson, SJ, Dinauer, MC, Williams, DA

Immunity 1999
15591124 Protein kinase Cdelta regulates p67phox phosphorylation in human monocytes

Zhao, X, Xu, B, Bhattacharjee, A, Oldfield, CM, Wientjes, FB, Feldman, GM, Cathcart, MK

J Leukoc Biol 2005
1660188 Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2

Knaus, UG, Heyworth, PG, Evans, T, Curnutte, JT, Bokoch, GM

Science 1991
8089108 The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases

el Benna, J, Faust, LP, Babior, BM

J Biol Chem 1994
18347018 Identification of a conserved Rac-binding site on NADPH oxidases supports a direct GTPase regulatory mechanism

Kao, YY, Gianni, D, Bohl, B, Taylor, RM, Bokoch, GM

J. Biol. Chem. 2008
23875749 Interaction of inducible nitric oxide synthase with rac2 regulates reactive oxygen and nitrogen species generation in the human neutrophil phagosomes: implication in microbial killing

Jyoti, A, Singh, AK, Dubey, M, Kumar, S, Saluja, R, Keshari, RS, Verma, A, Chandra, T, Kumar, A, Bajpai, VK, Barthwal, MK, Dikshit, M

Antioxid. Redox Signal. 2014
9804763 p40(phox) is phosphorylated on threonine 154 and serine 315 during activation of the phagocyte NADPH oxidase. Implication of a protein kinase c-type kinase in the phosphorylation process

Bouin, AP, Grandvaux, N, Vignais, PV, Fuchs, A

J. Biol. Chem. 1998
20813901 PtdIns3P and Rac direct the assembly of the NADPH oxidase on a novel, pre-phagosomal compartment during FcR-mediated phagocytosis in primary mouse neutrophils

Anderson, KE, Chessa, TA, Davidson, K, Henderson, RB, Walker, S, Tolmachova, T, Grys, K, Rausch, O, Seabra, MC, Tybulewicz, VL, Stephens, LR, Hawkins, PT

Blood 2010
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superoxide-generating NADPH oxidase activity of NOX2 complex:RAC2:GTP [phagocytic vesicle membrane]
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