MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines
MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines
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DOI：
10.1101/gad.888501
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发表时间：
2001-06-01
影响因子：
10.5
通讯作者：
Davis, RJ
中科院分区：
文献类型：
--
作者：
Tournier, C;Dong, C;Davis, RJ
丝裂原活化蛋白激酶（MAPK）是由MAPK激酶磷酸化Thr和Tyr而激活的。两种MAPK激酶（MKK4和MKK7）可以在体外激活c-run nh2末端激酶（JNK）组。MKK4优先磷酸化TNK在Tyr上，MKK7优先磷酸化Thr上。在小鼠中进行了靶向基因破坏研究，以检测MKK4和MKK7在体内的作用。需要同时破坏Mkk4和Mkk7基因来阻断由细胞暴露于环境应激引起的TNK激活。相反，仅破坏Mkk7基因就足以阻止促炎细胞因子引起的TNK激活。这些数据表明，MKK4和MKK7在JNK信号转导通路中具有不同的功能。
Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-run NH2-terminal kinase (JNK) group of MAPK in vitro. TNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block TNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent TNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.