Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin.
Calcium-dependent activation of TNF family gene expression by Ca2+/calmodulin kinase type IV/Gr and calcineurin.
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DOI：
10.4049/jimmunol.162.4.2057
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发表时间：
1999-02
影响因子：
4.4
通讯作者：
F. Lobo;R. Zanjani;N. Ho;T. Chatila;R. Fuleihan
中科院分区：
文献类型：
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作者：
F. Lobo;R. Zanjani;N. Ho;T. Chatila;R. Fuleihan
CD 40配体（L）、FasL和TNF-α是细胞因子TNF家族的成员。所有这些都在活化后不久由T淋巴细胞表达，但具有不同的效应子功能。这些基因的转录可以通过单独的钙离子载体刺激T细胞来诱导，并且需要活化的T细胞的钙调神经磷酸酶依赖性转录因子NF。我们已经研究了第二个钙依赖性信号通路，介导的钙/钙调蛋白依赖性激酶IV（CaMKIV）的TNF家族基因的转录激活。在使用由人CD 40 L、FasL或TNF-α的启动子驱动的构建体沿着表达组成型活性CaMKIV和钙调神经磷酸酶的载体的报告基因测定中，我们已经证明了每个启动子以协同方式被钙调神经磷酸酶和CaMKIV激活。此外，通过化学手段和通过CaMKIV的显性负突变体特异性抑制CaMKIV损害了所有三种启动子的离子霉素诱导的活性以及CD 40 L和TNF-α的蛋白质表达。我们的研究结果表明，激活基因表达的钙调磷酸酶和CaMKIV是常见的TNF细胞因子家族的成员。
CD40 ligand (L), FasL, and TNF-alpha 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-alpha 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-alpha. Our results indicate that activation of gene expression by calcineurin and CaMKIV is common to members of the TNF cytokine family.