T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase activation
T cell proliferation in response to interleukins 2 and 7 requires p38MAP kinase activation
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DOI：
10.1074/jbc.272.23.15023
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发表时间：
1997-06-06
影响因子：
4.8
通讯作者：
Foxwell, BMJ
中科院分区：
文献类型：
--
作者：
Crawley, JB;Rawlinson, L;Foxwell, BMJ
白细胞介素-2 （IL-2）是一种有效的T细胞分裂原。然而，IL-2介导其有丝分裂作用的信号通路尚不完全清楚。裂丝原活化蛋白激酶（MAPK）家族的成员之一p42/44MAPK （ERK2/1）已知可被IL-2激活。我们现在研究了MAP激酶家族的另外两个成员p54MAP激酶(应激激活蛋白激酶（SAPK)/ jun - n-末端激酶（JNK））和p38MAP激酶（p38/Mpk2/CSBP/RK）对IL-2的反应，它们主要对应激和炎症刺激（如肿瘤坏死因子- α、IL-1和脂多糖）作出反应。本研究表明，IL-2和另一种T细胞生长因子IL-7可以激活SAPK/JNK和p38MAP激酶。此外，特异性吡啶基咪唑抑制剂SB203580抑制p38MAP激酶活性，阻止其下游效应物mapk活化蛋白激酶-2的激活，与抑制IL-2和il -7驱动的T细胞增殖相关。这些数据表明，在T细胞中，p38MAP激酶在有丝分裂信号的转导中起作用。
Interleukin-2 (IL-2) is a potent T cell mitogen. However, the signaling pathways by which IL-2 mediates its mitogenic effect are not fully understood. One of the members of the mitogen-activated protein kinase (MAPK) family, p42/44MAPK (ERK2/1), is known to be activated by IL-2. We have now investigated the response to IL-2 of two other members of the MAP kinase family, p54MAP kinase (stress-activated protein kinase (SAPK)/Jun-N-terminal kinase (JNK)) and p38MAP kinase (p38/Mpk2/CSBP/RK), which respond primarily to stressful and inflammatory stimuli (e.g. tumor necrosis factor-alpha, IL-1, and lipopolysaccharide). Here we show that IL-2, and another T cell growth factor, IL-7, activate both SAPK/JNK and p38MAP kinase. Furthermore, inhibition of p38MAP kinase activity with a specific pyrinidyl imidazole inhibitor SB203580 that prevents activation of its downstream effector, MAPK-activating protein kinase-2, correlated with suppression of IL-2- and IL-7-driven T cell proliferation. These data indicate that in T cells p38MAP kinase has a role in transducing the mitogenic signal.