Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor
Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor
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粒细胞集落刺激因子快速激活 STAT3 转录因子
DOI：
10.1182/blood.v84.6.1760.bloodjournal8461760
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发表时间：
1994
期刊：
影响因子：
20.3
通讯作者：
J. Rosen
中科院分区：
文献类型：
--
作者：
S. Tian;P. Lamb;H. Seidel;R. Stein;J. Rosen
粒细胞集落刺激因子(G-CSF)是一种糖蛋白，通过其受体(G-CSFR)信号通路刺激中性粒细胞的增殖和分化。虽然G-CSFR属于细胞因子受体超家族，缺乏细胞内的激活区，但G-CSF诱导的细胞蛋白酪氨酸磷酸化是其生物学活性的关键。我们在此报告JAK1和JAK2酪氨酸激酶在G-CSF诱导下被酪氨酸磷酸化。我们还证明，DNA结合蛋白STAT3(也称为急性时相反应因子[APRF]，由白细胞介素6激活)是G-CSF诱导酪氨酸磷酸化的早期靶点。G-CSF诱导了两个DNA结合复合体；主要复合体含有酪氨酸磷酸化的STAT3蛋白，而次要复合体似乎是STAT1(以前的P91，干扰素激活的DNA结合复合体的组成部分)和STAT3蛋白的异源二聚体。抗磷酸酪氨酸抗体干扰激活的STAT3的DNA结合活性，表明STAT3的酪氨酸磷酸化对DNA结合活性是重要的。这些结果证实了G-CSF激活的信号转导途径，并为G-CSF快速调控基因表达提供了机制。
Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that stimulates proliferation and differentiation of progenitor cells of neutrophils by signaling through its receptor (G-CSFR). Although the G- CSFR belongs to the cytokine receptor superfamily, which lacks an intracellular kinase domain, G-CSF-induced tyrosine phosphorylation of cellular proteins is critical for its biologic activities. We report here that JAK1 and JAK2 tyrosine kinases are tyrosine phosphorylated in response to G-CSF induction. We also demonstrate that the DNA-binding protein STAT3 (also called the acute-phase response factor [APRF], activated by interleukin-6) is an early target of G-CSF-induced tyrosine phosphorylation. G-CSF induces two DNA-binding complexes; the major complex contains tyrosine phosphorylated STAT3 protein and the minor complex appears to be a heterodimer of the STAT1 (previously p91, a component of DNA-binding complexes activated by interferons) and STAT3 proteins. Antiphosphotyrosine antibody interferes with the DNA binding activity of activated STAT3, indicating that tyrosine phosphorylation of STAT3 is important for the DNA binding activity. These results identify a signal transduction pathway activated in response to G-CSF and provide a mechanism for the rapid modulation of gene expression by G-CSF.