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.
UR - http://www.scopus.com/inward/record.url?scp=0033558075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033558075&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.162.4.2057
DO - 10.4049/jimmunol.162.4.2057
M3 - Article
C2 - 9973478
AN - SCOPUS:0033558075
SN - 0022-1767
VL - 162
SP - 2057
EP - 2063
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -