Oxidative activation of type III CD38 by NADPH oxidase–derived hydrogen peroxide in Ca2+ signaling

What is it about?

CD38 is a transmembrane protein that generates the Ca2+ messenger cADPR. Enigmatically, its catalytic domain is positioned towards the outside of the cell. A demonstration of type III CD38 could provide an explanation for the production of cADPR by an enzyme with a cytosolic oriented catalytic site. However, the question then is how type III CD38 is activated. Here, we demonstrate the mechanism by which type III CD38 is activated: H2O2 generated by Nox4 oxidizes and activates type III CD38 by forming a disulfide bond between Cys164/Cys177. These findings explain a novel model of cross-talk between ROS and Ca2+ signaling.

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