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 language | English (US) |
|---|---|
| Pages (from-to) | 2057-2063 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 162 |
| Issue number | 4 |
| State | Published - Feb 15 1999 |
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ASJC Scopus subject areas
- Immunology
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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 journal › Article
TY - JOUR
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.
PY - 1999/2/15
Y1 - 1999/2/15
N2 - 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.
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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M3 - Article
VL - 162
SP - 2057
EP - 2063
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -