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Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B/AP-1 in T cells
- Source :
- Biochemical and biophysical research communications. 199(2)
- Publication Year :
- 1994
-
Abstract
- Two cis-acting elements GM-kappa B/GC-box and CLE0, of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene are required for maximal induction in Jurkat T cells by costimulation with phorbol-12-myristate acetate (PMA) and Ca2+ ionophore (A23187). The GM-kappa B sequence is recognized by NF-kappa B, which is mainly induced by PMA. The CLE0 sequence interacts with factors, related to a PMA-induced AP-1 and a PMA/A23187-induced NF-AT. We examined whether signal transducing components in T cells can activate transcription of the GM-CSF gene. Cotransfection of NF-kappa B (p50/p65)- or AP-1 (c-Jun/c-Fos)-expression vectors into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did not stimulate transcription from the GM-CSF promoter. In contrast, cotransfection with a combination of NF-kappa B and AP-1 significantly augmented transcription from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 (AP-1/NF-AT). Expression of a constitutively active calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, potentiated by two fold the transcriptional activation by NF-kappa B/AP-1. Both constitutively active forms of CN and protein kinase C (PKC) synergistically activated transcription from the GM-CSF promoter. These results suggest that cooperation among NF-kappa B-, AP-1- and NF-AT-binding sequences is required for induction of the GM-CSF gene through PKC- and Ca2+-signaling pathways downstream of T cell activation.
- Subjects :
- Leukemia, T-Cell
Transcription, Genetic
Proto-Oncogene Proteins c-jun
T cell
T-Lymphocytes
Phosphatase
Molecular Sequence Data
Biophysics
Gene Expression
Biology
Transfection
Biochemistry
Jurkat cells
Cell Line
chemistry.chemical_compound
Mice
Transcription (biology)
medicine
Phosphoprotein Phosphatases
Tumor Cells, Cultured
Animals
Humans
Luciferases
Promoter Regions, Genetic
Molecular Biology
Protein kinase C
Calcimycin
Base Sequence
Models, Genetic
Calcineurin
NF-kappa B
Granulocyte-Macrophage Colony-Stimulating Factor
NF-κB
Cell Biology
Molecular biology
TATA Box
Coleoptera
medicine.anatomical_structure
chemistry
Oligodeoxyribonucleotides
Cell culture
Tetradecanoylphorbol Acetate
Calmodulin-Binding Proteins
Protein Kinases
Proto-Oncogene Proteins c-fos
Plasmids
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 199
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....29e6609afde2eb3574bebc410395b923