Requirement of MKK4 and MKK7 for CdCl2- or HgCl2-induced activation of c-Jun NH2-terminal kinase in mouse embryonic stem cells
Requirement of MKK4 and MKK7 for CdCl2- or HgCl2-induced activation of c-Jun NH2-terminal kinase in mouse embryonic stem cells
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DOI：
10.1016/j.toxlet.2004.04.033
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发表时间：
2004-09-10
影响因子：
3.5
通讯作者：
Nishina, H
中科院分区：
文献类型：
--
作者：
Matsuoka, M;Igisu, H;Nishina, H
c-Jun NH 2-末端激酶（JNK），也称为应激激活蛋白激酶（SAPK），主要由炎性细胞因子和环境应激（包括有毒金属暴露）激活。为了揭示上游激酶负责JNK激活有毒金属，磷酸化状态和JNK的活性进行了检查，在小鼠胚胎干细胞（ES）缺乏MKK 4或MKK 7暴露于氯化镉或氯化汞。氯化镉或氯化汞处理诱导JNK磷酸化的剂量和时间依赖性的方式在野生型ES细胞。在mkk 4（-/-）和mkk 7（-/-）ES细胞中，CdCl_2和HgCl_2诱导的JNK磷酸化和激活均受到明显抑制。而在CdCl_2和H-G处理的mkk 7（-/-）ES细胞中，JNK激活未被消除（分别抑制56%和78%）。这些研究结果表明，通过有毒金属暴露的JNK的完全激活需要MKK 4和MKK 7，并且这些上游激酶可能在暴露于CdCl 2和HgCl 2的小鼠ES细胞之间的JNK激活中有差异。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
c-Jun NH2-terminal kinase (JNK), also known as stress-activated protein kinase (SAPK), is activated primarily by inflammatory cytokines and environmental stresses including toxic metal exposure. To reveal the upstream kinase responsible for JNK activation by toxic metals, the phosphorylation status and the activity of JNK were examined in mouse embryonic stem (ES) cells lacking MKK4 or MKK7 following exposure to CdCl2 or HgCl2. Treatment with CdCl2 or HgCl2 induced the phosphorylation of JNK in a dose- and time-dependent manner in wild-type ES cells. In both mkk4(-/-) and mkk7(-/-) ES cells, CdCl2- or HgCl2-incluced phosphorylation and activation of JNK were suppressed significantly. However, in mkk7(-/-) ES cells treated with CdCl2 and H-G,. JNK activation was not abolished (Suppressed by 56% and 78%, respectively). These findings suggest that the full activation of INK by toxic metal exposure requires both MKK4 and MKK7, and these upstream kinases might contribute differentially in JNK activation between mouse ES cells exposed to CdCl2 and HgCl2. (C) 2004 Elsevier Ireland Ltd. All rights reserved.