Moriguchi T, Toyoshima F, Masuyama N, Hanafusa H, Gotoh Y, Nishida E
Institute for Virus Research, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan.
EMBO J. 1997 Dec 1;16(23):7045-53. doi: 10.1093/emboj/16.23.7045.
Stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), a member of the MAP kinase (MAPK) superfamily, is thought to play a key role in a variety of cellular responses. To date, SEK1/MKK4, one of the MAP kinase kinase (MAPKK) family of molecules, is the only SAPK/JNK kinase that has been cloned. Here we have cloned, identified and characterized a novel member of the mammalian MAPKKs, designated MKK7. MKK7 is most similar to the mediator of morphogenesis, hemipterous (hep), in Drosophila. Immunochemical studies have identified MKK7 as one of the major SAPK/JNK-activating kinases in osmotically shocked cells. While SEK1/MKK4 can activate both the SAPK/JNK and p38 subgroups of the MAPK superfamily, MKK7 is specific for the SAPK/JNK subgroup. MKK7 is activated strongly by tumour necrosis factor alpha (TNFalpha) as well as by environmental stresses, whereas SEK1/MKK4 is not activated by TNFalpha. Column fractionation studies have shown that MKK7 is a major activator for SAPK/JNK in the TNFalpha-stimulated pathway. Moreover, we have found that overexpression of MKK7 enhances transcription from an AP-1-dependent reporter construct. Thus, MKK7 is an evolutionarily conserved MAPKK isoform which is specific for SAPK/JNK, is involved in AP-1-dependent transcription and may be a crucial mediator of TNFalpha signalling.
应激激活蛋白激酶（SAPK）/c-Jun氨基末端激酶（JNK）是丝裂原活化蛋白激酶（MAPK）超家族的成员之一，被认为在多种细胞反应中起关键作用。迄今为止，丝裂原活化蛋白激酶激酶（MAPKK）家族分子之一的SEK1/MKK4是唯一已被克隆的SAPK/JNK激酶。在此，我们克隆、鉴定并表征了哺乳动物MAPKKs的一个新成员，命名为MKK7。MKK7与果蝇中形态发生的介质半翅目（hep）最为相似。免疫化学研究已将MKK7鉴定为渗透休克细胞中主要的SAPK/JNK激活激酶之一。虽然SEK1/MKK4可以激活MAPK超家族的SAPK/JNK和p38亚组，但MKK7对SAPK/JNK亚组具有特异性。MKK7被肿瘤坏死因子α（TNFα）以及环境应激强烈激活，而SEK1/MKK4不被TNFα激活。柱分级分离研究表明，MKK7是TNFα刺激途径中SAPK/JNK的主要激活剂。此外，我们发现MKK7的过表达增强了来自AP-1依赖性报告构建体的转录。因此，MKK7是一种进化保守的MAPKK异构体，对SAPK/JNK具有特异性，参与AP-1依赖性转录，可能是TNFα信号传导的关键介质。
