Paper | January 13, 2026
NAADP synthesis by DUOX2
Project P03 published the mechanisms underlying activation of the NAADP-forming enzyme DUOX2. In addition to Ca2+ itself, the protein kinases PKA Cβ2 and PKCθ phosphorylate DUOX2 at Thr789 for full enzymatic activation. Whereas PKA Cβ2 is activated via adenosine A2A receptors, PKCθ is phosphorylated by the tyrosine kinase LCK downstream of T cell receptor (TCR) signaling. DUOX2 thereby functions as a coincidence detector that integrates TCR- dependent and -independent signals.
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Multiple signaling events are required for NAADP synthesis by DUOX2 and formation of Ca2+ microdomains to initiate T cell activation. Winterberg K.J., Schwentner V., Gu F. et al. Sci Signal. 19, eadp4326 (2026).
