Coupling of Ca(2+) microdomains to spatially and temporally distinct cellular responses by the tyrosine kinase Syk.
Ng SW., Nelson C., Parekh AB.
Communication between the cell surface and the nucleus is essential for regulated gene expression. In neurons, Ca(2+)-dependent gene transcription is sensitive to local Ca(2+) entry. In immune cells, excitation-transcription coupling is thought to involve global Ca(2+) signals. Here, we show that in mast cells, Ca(2+) microdomains from store-operated Ca(2+) release-activated Ca(2+) channels activate expression of the transcription factor c-fos. Local Ca(2+) entry is sensed by the tyrosine kinase Syk, which signals to the nucleus through the transcription factor STAT5. Ca(2+) microdomains also promote secretion of proinflammatory messengers, which, like gene expression, requires Syk. Syk therefore couples Ca(2+) microdomains to the activation of two spatially and temporally distinct cellular responses, revealing the versatility of local Ca(2+) signals in driving cell activation.