Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha.

Interleukin-5 signaling in human eosinophils involves JAK2 tyrosine kinase and Stat1 alpha.
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人嗜酸性粒细胞中的 IL-5 信号传导涉及 JAK2 酪氨酸激酶和 Stat1 α。

DOI:
10.1182/blood.v85.6.1442.bloodjournal8561442
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发表时间:
1995
期刊:
影响因子:
20.3
通讯作者:
L. Koenderman
L. Koenderman
中科院分区:
医学1区
文献类型:
--
作者:
T. Bruggen;E. Caldenhoven;D. Kanters;P. Coffer;J. Raaijmakers;Jan;L. Koenderman

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通过多种细胞因子(包括干扰素、白介素和生长因子)的信号传导涉及JAK激酶和Stat(信号转导和转录激活因子)蛋白的激活。目前,对白细胞介素-5(IL-5)发挥其多种生物学作用的分子机制了解不多。人嗜酸性粒细胞是IL-5最重要的靶细胞之一,在此用于研究原代人细胞中的IL-5信号传导。IL-5诱导JAK 2的快速和短暂的酪氨酸磷酸化。此外,IL-5诱导至少两个DNA结合复合物,使用正常人嗜酸性粒细胞的核提取物和IL-6/干扰素-γ响应元件的ICAM-1启动子(ICAM-1 pIRE)在电迁移率变动测定。从超位移实验得出的结论是,一个DNA结合复合物含有Stat 1 α,可能作为一个同源二聚体。两种DNA结合复合物被磷酸酪氨酸抗体(4G 10)抑制,表明酪氨酸磷酸化是复合物形成所必需的。与IL-5相似,IL-3和粒细胞-巨噬细胞集落刺激因子诱导人嗜酸性粒细胞中的两种DNA结合复合物,包括Stat 1 α。这些数据首次表明,人嗜酸性粒细胞中IL-5信号传导的分子机制涉及JAK激酶家族的成员以及Stat家族的成员。
Signaling by a wide variety of cytokines, including interferons, interleukins, and growth factors, involves activation of JAK kinases and Stat (Signal transducers and activators of transcription) proteins. At present, not much is known about the molecular mechanisms by which interleukin-5 (IL-5) exerts its diverse biologic effects. Human eosinophils are one of the most important target cells for IL-5 and were used here to study IL-5 signaling in a primary human cell. IL-5 induced rapid and transient tyrosine phosphorylation of JAK2. Moreover, IL-5 induced at least two DNA-binding complexes, using nuclear extracts from normal human eosinophils and the IL-6/interferon-gamma response element of the ICAM-1 promoter (ICAM-1 pIRE) in an electromobility shift assay. From supershift experiments it was concluded that one DNA-binding complex contained Stat1 alpha, probably as a homodimer. Both DNA-binding complexes were inhibited by a phosphotyrosine antibody (4G10), suggesting that tyrosine phosphorylation is required for complex formation. IL-3 and granulocyte-macrophage colony-stimulating factor induced, similar to IL-5, two DNA-binding complexes in human eosinophils, including Stat1 alpha. These data show for the first time that molecular mechanisms of IL-5 signaling in human eosinophils involve members of the JAK kinase family as well as members of the Stat family.
Interleukin-3 调节髓系白血病细胞系中 LYN 蛋白酪氨酸激酶的活性。
DOI: --
发表时间: 1992
期刊: Blood
影响因子: 20.3
作者:
Torigoe,T;O'Connor,R;Santoli,D;Reed,JC
通讯作者: Reed,JC
DOI: 10.1126/science.7690989
发表时间: 1993-09-24
期刊: SCIENCE
影响因子: 56.9
作者:
SHUAI, K;STARK, GR;DARNELL, JE
通讯作者: DARNELL, JE
粒细胞-巨噬细胞集落刺激因子、白介素-3 和钢因子诱导 p42 和 p44 MAP 激酶的快速酪氨酸磷酸化。
DOI: --
发表时间: 1992
期刊: Blood
影响因子: 20.3
作者:
Okuda,K;Sanghera,JS;Pelech,SL;Kanakura,Y;Hallek,M;Griffin,JD;Druker,BJ
通讯作者: Druker,BJ
DOI: 10.1073/pnas.87.21.8555
发表时间: 1990-11-01
影响因子: 11.1
作者:
FU, XY;KESSLER, DS;DARNELL, JE
通讯作者: DARNELL, JE
DOI: 10.1016/0091-6749(90)90151-s
发表时间: 1990-02-01
影响因子: 14.2
作者:
GLEICH, GJ
通讯作者: GLEICH, GJ