ROCK2 interacts with p22phox to phosphorylate p47phox and to control NADPH oxidase activation in human monocytes

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Tlili, Asma | Pintard, Coralie | Hurtado-Nedelec, Margarita | Liu, Dan | Marzaioli, Viviana | Thieblemont, Nathalie | Dang, Pham My-Chan | El-Benna, Jamel

Edité par CCSD ; National Academy of Sciences -

International audience. Significance Monocytes play a key role in innate immunity and inflammation by producing reactive oxygen species (ROS). The enzyme responsible for ROS production is the phagocyte NADPH oxidase, which is composed of two membrane proteins (p22phox and gp91phox/NOX2) and four cytosolic proteins (p47phox, p67phox, p40phox, and Rac1/2). Here, we show that p22phox associates with Rho-associated coiled-coil kinase 2 (ROCK2) in human monocytes. Interestingly, ROCK2 does not phosphorylate p22phox, p40phox, p67phox or gp91phox in vitro but highly phosphorylates p47phox. Furthermore, selective inhibition of ROCK2 activity and expression, inhibited both ROS production and p47phox phosphorylation in human monocytes. These data identify a key role of ROCK2 in the regulation of ROS production by monocytes. The ROCK2-p22phox interaction could be used to target monocyte ROS production.

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