Dual modes of control of c-fos mRNA induction by intracellular calcium in T cells.
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.
Lee
G
G
Cold Spring Harbor Laboratory, New York 11724.
Gilman
M
M
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D010856:Columbidae; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D015290:Second Messenger Systems; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium