Activation of JNK signaling pathway by erythropoietin, thrombopoietin, and interleukin-3
Activation of JNK signaling pathway by erythropoietin, thrombopoietin, and interleukin-3
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DOI：
10.1182/blood.v89.8.2664
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发表时间：
1997-04-15
期刊：
影响因子：
20.3
通讯作者：
Todokoro, K
中科院分区：
文献类型：
--
作者：
Nagata, Y;Nishida, E;Todokoro, K
据报道，各种环境应激，如渗透休克、紫外线辐射和热休克，或促炎细胞因子肿瘤坏死因子- α和白细胞介素-1可诱导c-Jun氨基末端激酶（JNK）的激活，而JNK通常由SEK1/MKK4激活。我们在这里报道了造血细胞因子白介素-3 （IL-3）、促红细胞生成素（Epo）和血小板生成素（Tpo），它们分别调节造血祖细胞、红细胞和巨核细胞/血小板的生长和分化，也激活JNK信号级联。凝胶内激酶试验和体外激酶试验清楚地表明，IL-3、Epo和Tpo能够快速、短暂地激活IL-3、Epo或Tpo依赖性小鼠造血祖细胞中的JNK1和JNK2。然而，免疫印迹分析和体外激酶试验表明，IL-3、Epo或Tpo刺激既不能诱导SEK1/MKK4的磷酸化，也不能诱导其活化。我们得出结论，JNK信号级联不仅在应激反应和促炎细胞因子的作用中起重要作用，而且在造血细胞因子的作用中也起重要作用，并且造血细胞因子可能通过除SEK1/MKK4以外的激酶激活JNK，正如之前对应激激活细胞所提出的那样。(C) 1997年由美国血液病学会出版。
A variety of environmental stresses, such as osmotic shock, UV radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 reportedly induce activation of c-Jun amino-terminal kinases (JNK), which are usually activated by SEK1/MKK4. We report here that the hematopoietic cytokines interleukin-3 (IL-3), erythropoietin (Epo), and thrombopoietin (Tpo), which regulate growth and differentiation of hematopoietic progenitor cells, erythroids, and megakaryocytes/platelets, respectively, also activate a JNK signaling cascade. In-gel kinase assay as well as in vitro kinase assay clearly showed that IL-3, Epo, and Tpo rapidly and transiently activated both JNK1 and JNK2 in IL-3-, Epo-, or Tpo-dependent mouse hematopoietic progenitor cells, However, immunoblot analysis and in vitro kinase assay showed that neither phosphorylation nor activation of SEK1/MKK4 was induced by IL-3, Epo, or Tpo stimulation, Therefore, we concluded that the JNK signaling cascade plays an important role not only in stress responses and proinflammatory cytokine actions but also in hematopoietic cytokine actions and that hematopoietic cytokines may activate the JNKs through a kinase other than SEK1/MKK4, as previously suggested for stress-activated cells. (C) 1997 by The American Society of Hematology.