Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin

Francis M. Lobo, Reza Zanjani, Nga Ho, Talal A. Chatila, Ramsay L. Fuleihan*

*Corresponding author for this work

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

CD40 ligand (L), FasL, and TNF-α are members of the TNF family of cytokines. All are expressed by T lymphocytes shortly after activation but have distinct effector functions. Transcription of these genes can be induced by stimulation of T cells by calcium ionophore alone and requires the calcineurin-dependent transcription factor NF of activated T cells. We have examined a second calcium-dependent signaling pathway, mediated by calcium/calmodulin-dependent kinase IV (CaMKIV) in transcriptional activation of TNF family genes. In reporter gene assays using constructs driven by the promoters of human CD40L, FasL, or TNF-α along with vectors expressing constitutively active CaMKIV and calcineurin, we have demonstrated that each promoter is activated by calcineurin and CaMKIV in a synergistic fashion. Furthermore, specific inhibition of CaMKIV by chemical means and by a dominant negative mutant of CaMKIV impairs the ionomycin-induced activity of all three promoters as well as protein expression of CD40L and TNF-α. Our results indicate that activation of gene expression by calcineurin and CaMKIV is common to members of the TNF cytokine family.

Original languageEnglish (US)
Pages (from-to)2057-2063
Number of pages7
JournalJournal of Immunology
Volume162
Issue number4
StatePublished - Feb 15 1999

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Calcium-Calmodulin-Dependent Protein Kinases
Calcineurin
Calcium
Gene Expression
CD40 Ligand
T-Lymphocytes
Cytokines
Ionomycin
Calcium Signaling
Calcium Ionophores
Reporter Genes
Transcriptional Activation
Genes
Transcription Factors
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Lobo, Francis M. ; Zanjani, Reza ; Ho, Nga ; Chatila, Talal A. ; Fuleihan, Ramsay L. / Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin. In: Journal of Immunology. 1999 ; Vol. 162, No. 4. pp. 2057-2063.
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Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin. / Lobo, Francis M.; Zanjani, Reza; Ho, Nga; Chatila, Talal A.; Fuleihan, Ramsay L.

In: Journal of Immunology, Vol. 162, No. 4, 15.02.1999, p. 2057-2063.

Research output: Contribution to journalArticle

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T1 - Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin

AU - Lobo, Francis M.

AU - Zanjani, Reza

AU - Ho, Nga

AU - Chatila, Talal A.

AU - Fuleihan, Ramsay L.

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AB - CD40 ligand (L), FasL, and TNF-α are members of the TNF family of cytokines. All are expressed by T lymphocytes shortly after activation but have distinct effector functions. Transcription of these genes can be induced by stimulation of T cells by calcium ionophore alone and requires the calcineurin-dependent transcription factor NF of activated T cells. We have examined a second calcium-dependent signaling pathway, mediated by calcium/calmodulin-dependent kinase IV (CaMKIV) in transcriptional activation of TNF family genes. In reporter gene assays using constructs driven by the promoters of human CD40L, FasL, or TNF-α along with vectors expressing constitutively active CaMKIV and calcineurin, we have demonstrated that each promoter is activated by calcineurin and CaMKIV in a synergistic fashion. Furthermore, specific inhibition of CaMKIV by chemical means and by a dominant negative mutant of CaMKIV impairs the ionomycin-induced activity of all three promoters as well as protein expression of CD40L and TNF-α. Our results indicate that activation of gene expression by calcineurin and CaMKIV is common to members of the TNF cytokine family.

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