Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway

Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway
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DOI:
10.1126/science.278.5343.1638
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发表时间:
1997-11-28
期刊:
影响因子:
56.9
通讯作者:
Davis, RJ
Davis, RJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chow, CW;Rincon, M;Davis, RJ

文献摘要

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活化T细胞核因子(NFAT)类转录因子被保留在静止期细胞的胞浆中,NFAT的激活部分是通过诱导核输入来介导的,这一过程需要钙依赖的NFAT去磷酸化由磷酸酶钙调神经磷酸酶(Calcineurin)引起,c-Jun氨基末端激酶(JNK)在两个位点上磷酸化NFAT4,JNK磷酸化位点的突变去除导致NFAT4的组成性核定位,相反,在钙调神经磷酸酶刺激的细胞中JNK激活导致NFAT4的核排斥。这些发现表明,钙调神经磷酸酶促进的NFAT4的核积聚与JNK信号转导途径相反。
The nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells, NFAT activation is mediated in part, by induced nuclear import, This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin, The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites, Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4, in contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway.