Acute phase response factor and additional members of the interferon-stimulated gene factor 3 family integrate diverse signals from cytokines, interferons, and growth factors.
Acute phase response factor and additional members of the interferon-stimulated gene factor 3 family integrate diverse signals from cytokines, interferons, and growth factors.
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DOI：
10.1016/s0021-9258(19)51096-1
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发表时间：
1994-09
期刊：
影响因子：
--
通讯作者：
R. Raz;J. Durbin;D. Levy
中科院分区：
文献类型：
--
作者：
R. Raz;J. Durbin;D. Levy
细胞因子和生长因子通过诱导基因表达来引起靶细胞的反应。导致细胞表面受体基因转录的信号传导机制通常需要酪氨酸磷酸化。包含干扰素 (IFN) 刺激的基因因子 3 (ISGF3) 多聚体复合物的转录因子家族在干扰素的作用下被磷酸化和激活。我们描述了一种与构成急性期反应因子 (APRF) 的 ISGF3 91-kDa 亚基 50% 相同的蛋白质。这种蛋白质被白细胞介素 6 迅速激活，以结合炎症急性期反应期间肝细胞中激活的基因所共有的增强子元件。值得注意的是，APRF 也被 IFN α、IFN γ、表皮生长因子、血小板源性生长因子、集落刺激因子-1、细胞因子白血病抑制因子和制瘤素 M 激活。除了 APRF 和 p91 之外，生长因子还激活第三种不同但相关的 DNA 结合蛋白。这一新因子或密切相关的因子（但既不是 APRF 也不是 p91）在淋巴细胞中也被白细胞介素 2、促红细胞生成素和白细胞介素 3 激活。因此，APRF、p91 和 ISGF3 家族其他成员的激活是多种信号传导途径的普遍特征，通过常见的转录调节因子整合不同的信号。
Cytokines and growth factors elicit responses in target cells through induction of gene expression. Signaling mechanisms leading to gene transcription from cell surface receptors often require tyrosine phosphorylation. A family of transcription factors comprising the interferon (IFN)-stimulated gene factor 3 (ISGF3) multimeric complex are phosphorylated and activated in response to interferon. We describe a protein 50% identical to the 91-kDa subunit of ISGF3 that constitutes the acute phase response factor (APRF). This protein was rapidly activated by interleukin-6 to bind an enhancer element common to genes activated in liver cells during the acute phase response to inflammation. Remarkably, APRF was also activated by IFN alpha, IFN gamma, epidermal growth factor, platelet-derived growth factor, colony stimulating factor-1, and the cytokines leukemia inhibitory factor and oncostatin M. The growth factors also activated a third, distinct but related, DNA-binding protein in addition to APRF and p91. This novel factor or a closely related one, but neither APRF nor p91, was also activated in lymphoid cells by interleukin-2, erythropoietin, and interleukin-3. Activation of APRF, p91, and additional members of the ISGF3 family is thus a general feature of a wide variety of signaling pathways, integrating diverse signals through common transcriptional regulators.