Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3
Activation of p38 MAP kinase pathway by erythropoietin and interleukin-3
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DOI：
10.1182/blood.v90.3.929.929_929_934
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发表时间：
1997-08-01
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;Moriguchi, T;Todokoro, K
p38 MAP激酶（p38）以及JNK/SAPK的激活被描述为由多种环境应激（例如渗透压休克、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（IL-3）诱导。我们发现，造血细胞因子促红细胞生成素（Epo）和IL-3，分别调节红细胞和造血祖细胞的生长和分化，也激活p38级联。免疫印迹分析和体外激酶试验清楚地表明，Epo和IL-3迅速和瞬时磷酸化和激活Epo或IL-3依赖的小鼠造血祖细胞中的p38。p38通常可被上游激酶MKK 3或MKK 6激活。然而，在用抗MKK 6抗体和抗磷酸化的MKK 3/MKK 6抗体的免疫沉淀物中的体外激酶测定显示，在Epo或IL-3刺激后既未检测到MKK 3也未检测到MKK 6的激活，而渗透压休克明显诱导MKK 3/MKK 6和p38两者的激活。结合之前的观察，这些结果表明p38和JNK级联不仅在应激和促炎细胞因子反应中发挥重要作用，而且在造血细胞因子作用中也发挥重要作用。(C)1997年，美国血液学会。
Activation of p38 MAP kinase (p38) as well as JNK/SAPK has been described as being induced by a variety of environmental stresses such as osmotic shock, ultraviolet radiation, and heat shock, or the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 (IL-3). We found that the hematopoietic cytokines erythropoietin (Epo) and IL-3, which regulate growth and differentiation of erythroids and hematopoietic progenitors, respectively, also activate a p38 cascade. Immunoblot analyses and in vitro kinase assay clearly showed that Epo and IL-3 rapidly and transiently phosphorylated and activated p38 in Epo- or IL-3-dependent mouse hematopoietic progenitor cells. p38 can generally be activated by the upstream kinase MKK3 or MKK6, However, in vitro kinase assays in the immunoprecipitates with anti-MKK6 antibody and anti-phosphorylated MKK3/MKK6 antibody showed that activation of neither MKK3 nor MKK6 was detected after Epo or IL-3 stimulation, while osmotic shock clearly induced activation of both MKK3/MKK6 and p38. Together with previous observations, these results suggest that both p38 and JNK cascades play an important role not only in stress and proinflammatory cytokine responses but also in hematopoietic cytokine actions. (C) 1997 by The American Society of Hematology.