Different agonists recruit different stromal interaction molecule proteins to support cytoplasmic Ca oscillations and gene expression

Stimulation of cells with physiological concentrations of calciummobilizing agonists often results in the generation of repetitive cytoplasmic Ca oscillations. Although oscillations arise from regenerative Ca release, they are sustained by store-operated Ca entry through Ca release-activated Ca (CRAC) channels. Here, we show that following stimulation of cysteinyl leukotriene type I receptors in rat basophilic leukemia (RBL)-1 cells, large amplitude Ca oscillations, CRAC channel activity, and downstream Ca-dependent nuclear factor of activated T cells (NFAT)-driven gene expression are all exclusively maintained by the endoplasmic reticulum Ca sensor stromal interaction molecule (STIM) 1. However, stimulation of tyrosine kinase-coupled FCεRI receptors evoked Ca oscillations and NFAT-dependent gene expression through recruitment of both STIM2 and STIM1. We conclude that different agonists activate different STIM proteins to sustain Ca signals and downstream responses.