Coupling of Ca2+ Microdomains to Spatially and Temporally Distinct Cellular Responses by the Tyrosine Kinase Syk

Communication between the cell surface and the nucleus is essential for regulated gene expression. In neurons, Ca2+-dependent gene transcription is sensitive to local Ca2+ entry. In immune cells, excitation-transcription coupling is thought to involve global Ca2+ signals. Here, we show that in mast cells, Ca2+ microdomains from store-operated Ca2+ release-activated Ca2+ channels activate expression of the transcription factor c-fos. Local Ca2+ entry is sensed by the tyrosine kinase Syk, which signals to the nucleus through the transcription factor STAT5. Ca2+ microdomains also promote secretion of proinflammatory messengers, which, like gene expression, requires Syk. Syk therefore couples Ca2+ microdomains to the activation of two spatially and temporally distinct cellular responses, revealing the versatility of local Ca2+ signals in driving cell activation.