Northrop J P, Ho S N, Chen L, Thomas D J, Timmerman L A, Nolan G P, Admon A, Crabtree G R
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University Medical School, California 94305.
Nature. 1994 Jun 9;369(6480):497-502. doi: 10.1038/369497a0.
The NF-AT transcription complex is required for the expression of a group of proteins that collectively coordinate the immune response. Here we purify two proteins encoded by separate genes that represent the pre-existing (p) and cytosolic (c) components of NF-AT. Expression of the full-length complementary DNA encoding NF-ATc activates the interleukin (IL-2) promoter in non-T lymphocytes, whereas a dominant negative of NF-ATc specifically blocks activation of the IL-2 promoter in T lymphocytes, indicating that NF-ATc is required for IL-2 gene expression. NF-ATc RNA expression is largely restricted to lymphoid tissues and is induced upon T-cell activation. The other protein, NF-ATp, is highly homologous to NF-ATc over a limited domain which shows similarity to the Dorsal/Rel family, but has a wider tissue distribution. Agents that increase intracellular Ca2+ or activate protein kinase C independently modify NF-ATc, indicating that distinct signalling pathways converge on NF-ATc to regulate its function.
NF-AT转录复合体是一组共同协调免疫反应的蛋白质表达所必需的。在这里，我们纯化了由不同基因编码的两种蛋白质，它们分别代表NF-AT的预先存在的（p）和胞质（c）成分。编码NF-ATc的全长互补DNA的表达可激活非T淋巴细胞中的白细胞介素（IL-2）启动子，而NF-ATc的显性负性突变体则特异性地阻断T淋巴细胞中IL-2启动子的激活，这表明IL-2基因表达需要NF-ATc。NF-ATc RNA表达主要局限于淋巴组织，并在T细胞激活时被诱导。另一种蛋白质NF-ATp在与Dorsal/Rel家族相似的有限结构域内与NF-ATc高度同源，但具有更广泛的组织分布。增加细胞内Ca2+或激活蛋白激酶C的试剂可独立修饰NF-ATc，这表明不同的信号通路汇聚于NF-ATc以调节其功能。
