Coupling of Ca(2+) 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, 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.
Ng
Siaw-Wei
SW
Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom.
Nelson
Charmaine
C
Parekh
Anant B
AB
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072377:Syk Kinase; D013997:Time Factors; D014158:Transcription, Genetic
D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium