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. 1994 Jul;14(7):4579–4587. doi: 10.1128/mcb.14.7.4579

Dual modes of control of c-fos mRNA induction by intracellular calcium in T cells.

G Lee 1, M Gilman 1
PMCID: PMC358830  PMID: 8007962

Abstract

Cytoplasmic calcium is a nearly universal second messenger in eukaryotes. In many cell types, elevated intracellular calcium interacts synergistically with inducers of protein kinase C to elicit activation of complete biological programs normally induced by extracellular signals. In T cells, elevated cytoplasmic calcium is a critical mediator of activation in response to stimulation of the antigen receptor, and in some T-cell lines, treatment with a combination of calcium ionophore and protein kinase C activator mimics authentic antigen treatment. The synergistic interaction of calcium and protein kinase C in T cells is also observed at the level of gene expression. Here we examine the molecular mechanisms through which these agents exert synergistic control over the expression of the c-fos proto-oncogene in a T-cell hybridoma. We find that the principal effect of calcium is on the elongation of c-fos transcripts. This step constitutes the major control of c-fos mRNA accumulation in these cells. In addition, calcium regulates the initiation of c-fos transcription. This effect requires the serum response element of the c-fos gene and an additional sequence immediately 3' to this element. Thus, calcium regulates c-fos expression through at least two distinct molecular pathways.

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