Receptor to nucleus signaling by prolactin and interleukin 2 via activation of latent DNA-binding factors.
Receptor to nucleus signaling by prolactin and interleukin 2 via activation of latent DNA-binding factors.
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通过激活潜在 DNA 结合因子，催乳素和白细胞介素 2 的细胞核信号转导受体。
DOI：
10.1073/pnas.91.15.6850
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发表时间：
1994
影响因子：
11.1
通讯作者：
Reich,NC
中科院分区：
文献类型：
--
作者：
Gilmour,KC;Reich,NC
催乳素(PRL)是一种促乳素和免疫调节激素，尽管它在发育中起着关键作用，但其作用机制仍不清楚。这项研究确定了一种由PRL诱导的DNA结合因子，它似乎介导了从细胞表面受体到细胞核中特定基因表达的信号。PRL刺激NB2 T淋巴瘤细胞的增殖，并激活干扰素调节因子1(IRF-1)基因的转录。在PRL刺激的几分钟内，PRL诱导因子(PRLIF)被激活并结合到IRF-1基因启动子的靶点。PRLIF结合位点包含一个反向GAAA重复序列，该重复序列在激素反应的β-酪蛋白基因中也具有功能。PRL-受体复合体信号传递JAK2的酪氨酸磷酸化信号，JAK2是一种非受体酪氨酸激酶，可能导致PRLIF的激活。T细胞增殖和IRF-1基因的转录激活也是由细胞因子白介素2(IL-2)诱导的。这份报告证明了一种识别IRF-1启动子中相同GAAA反向重复的IL-2核激活因子的快速激活。PRLIF和IL-2核活化因子是新近发现的因子，它们分别在PRL和IL-2的信号转导通路中发挥基础作用，导致反应基因的转录调控。
The mechanism of action of prolactin (PRL), a lactogenic and immunoregulatory hormone, has remained undetermined despite its critical role in development. This study identifies a DNA-binding factor induced by PRL that appears to mediate a signal from the cell surface receptor to specific gene expression in the nucleus. PRL stimulates the proliferation of Nb2 T-lymphoma cells and activates transcription of the interferon-regulatory factor 1 (IRF-1) gene. Within minutes of PRL stimulation, a PRL-induced factor (PRLIF) is activated and binds to a target site in the promoter of the IRF-1 gene. The PRLIF-binding site contains an inverted GAAA repeat that is also functional in the hormone-responsive beta-casein gene. The PRL-receptor complex signals tyrosine phosphorylation of JAK2, a nonreceptor tyrosine kinase, which may lead to activation of PRLIF. T-cell proliferation and transcriptional activation of the IRF-1 gene is also induced by the cytokine interleukin 2 (IL-2). This report demonstrates the rapid activation of an IL-2 nuclear-activated factor that recognizes the same GAAA inverted repeat in the IRF-1 promoter. PRLIF and IL-2 nuclear-activated factor are newly identified factors that appear to serve fundamental roles in the signal transduction pathways of PRL and IL-2, respectively, leading to the transcriptional regulation of responsive genes.