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

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

Stable Identifier

R-HSA-5668629

Type

Reaction [transition]

Species

Homo sapiens

Compartment

phagolysosome, phagocytic vesicle membrane, cytosol, phagocytic vesicle

ReviewStatus

5/5

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

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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
10072071	Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense Kim, C, Zhen, L, Kapur, R, Dinauer, MC, Petryniak, B, Williams, DA, Roberts, AW, Spaetti, A, Pollock, JD, Lowe, JB, Borneo, JB, Bradford, GB, Atkinson, SJ	Immunity	1999
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
15591124	Protein kinase Cdelta regulates p67phox phosphorylation in human monocytes Bhattacharjee, A, Feldman, GM, Wientjes, FB, Oldfield, CM, Zhao, X, Xu, B, Cathcart, MK	J Leukoc Biol	2005
1660188	Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2 Bokoch, GM, Curnutte, JT, Evans, T, Knaus, UG, Heyworth, PG	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 Faust, LP, el Benna, J, Babior, BM	J Biol Chem	1994
18347018	Identification of a conserved Rac-binding site on NADPH oxidases supports a direct GTPase regulatory mechanism Bohl, B, Taylor, RM, Gianni, D, Bokoch, GM, Kao, YY	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 Chandra, T, Dubey, M, Kumar, S, Keshari, RS, Jyoti, A, Verma, A, Saluja, R, Kumar, A, Singh, AK, Bajpai, VK, Dikshit, M, Barthwal, MK	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 Fuchs, A, Bouin, AP, Vignais, PV, Grandvaux, N	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 Seabra, MC, Grys, K, Walker, S, Tybulewicz, VL, Anderson, KE, Davidson, K, Henderson, RB, Hawkins, PT, Chessa, TA, Rausch, O, Stephens, LR, Tolmachova, T	Blood	2010