Reactome | MAPK1 or MAPK3 phosphorylates NCF1 at Ser345

MAPK1 or MAPK3 phosphorylates NCF1 at Ser345

Stable Identifier

R-HSA-9626832

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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MAPK1 or MAPK3 phosphorylates NCF1 at Ser345

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In resting cells, the NADPH oxidase components, NCF1 (p47phox), NCF2 (p67phox), and NCF4 (p40phox) are located in the cytosol where they associate in a trimer complex with a 1:1:1 stoichiometry through specific domains (Groemping Y & Rittinger K 2005; El-Benna J et al. 2005; Park JW et al. 1994; Lapouge K et al. 2002; El-Benna J et al. 2016). However, NCF1 may also exist separately from the trimer (El-Benna J et al. 2016). In the resting state, two SH3 domains of NCF1 (p47phox) bind the auto‐inhibitory region (AIR; amino acids 292‐340) to keep NCF1 in a closed auto‐inhibited state, preventing its binding to p22phox and therefore NOX2 activation (Groemping Y et al. 2003; Yuzawa S et al. 2004; El-Benna J et al. 2016). Priming of neutrophils by several agents such as GM‐CSF, TNFα, PAF, LPS and CL097, a TLR7/8 agonist, induces partial phosphorylation of NCF1 (Makni-Maalej K et al. 2015; Dang PM et al. 1999; Dewas C et al. 2003; DeLeo FR et al. 1998). Mass spectrometry analysis of NCF1 identified Ser345 as the phosphorylated site in neutrophils primed by TNFα and GM‐CSF, and site‐directed mutagenesis of Ser345 and use of a competitive inhibitory peptide containing the Ser345 sequence have demonstrated that this step is critical for the priming of ROS production in human neutrophils (Dang PMC et al. 2006). Further, inhibitors of the MAPK1 and MAPK3 (ERK1/2) pathway abrogated GM-CSF-induced phosphorylation of Ser345 (Dang PMC et al. 2006).

Literature References

PubMed ID	Title	Journal	Year
16778989	A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites Dang, PM, Stensballe, A, Boussetta, T, Raad, H, Dewas, C, Kroviarski, Y, Hayem, G, Jensen, ON, Gougerot-Pocidalo, MA, El-Benna, J	J. Clin. Invest.	2006
27558335	Priming of the neutrophil respiratory burst: role in host defense and inflammation El-Benna, J, Hurtado-Nedelec, M, Marzaioli, V, Marie, JC, Gougerot-Pocidalo, MA, Dang, PM	Immunol. Rev.	2016
10400704	Priming of human neutrophil respiratory burst by granulocyte/macrophage colony-stimulating factor (GM-CSF) involves partial phosphorylation of p47(phox) Dang, PM, Dewas, C, Gaudry, M, Fay, M, Pedruzzi, E, Gougerot-Pocidalo, MA, El Benna, J	J. Biol. Chem.	1999