Dynamic control of NAADP signaling by kinases in T cells.

In T cells, Dual Oxidase 2 (DUOX2) is responsible for reducing NAADPH to NAADP, a potent second messenger that evokes Ca2+ signaling. However, specific DUOX2 activation mechanisms, particularly upon T-cell receptor (TCR) activation, remained unclear. New findings from Winterberg K. et al. identify two key kinases, PKCθ and PKA Cβ2, that directly phosphorylate and activate DUOX2, thereby accounting for basal TCR-independent and TCR-evoked NAADP/Ca2+ signaling and dictating cytokine production.