A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK
A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK
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DOI：
10.1093/emboj/20.19.5421
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发表时间：
2001-10-01
期刊：
影响因子：
11.4
通讯作者：
Matsumoto, K
中科院分区：
文献类型：
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作者：
Inoue, H;Tateno, M;Matsumoto, K
在培养的哺乳动物细胞中，p38丝裂原活化蛋白激酶（MAPK）途径被激活，以响应各种环境压力。然而，很少有证据表明，在体内研究中的压力反应，这一途径的作用。我们发现了一种能激活p38 MAPK的果蝇MAPK激酶激酶D-MEKK 1。D-MEKK 1在结构上类似于哺乳动物MEKK 4/MTK 1 MAPKKK。在高渗透压条件下，动物体内D-MEKK 1激酶活性被激活。缺乏D-MEKK 1的果蝇突变体对环境胁迫（包括升高的温度和增加的渗透压）超敏感。在这些D-MEKK 1突变体中，与野生型动物相比，果蝇p38 MAPK在应激反应中的激活较差。这些结果表明，D-MEKK 1调节p38 MAPK通路是关键的果蝇对环境压力的反应。
In cultured mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses. However, there is little evidence from in vivo studies to demonstrate a role for this pathway in the stress response. We identified a Drosophila MAPK kinase kinase (MAPKKK), D-MEKK1, which can activate p38 MAPK. D-MEKK1 is structurally similar to the mammalian MEKK4/MTK1 MAPKKK. D-MEKK1 kinase activity was activated in animals under conditions of high osmolarity. Drosophila mutants lacking D-MEKK1 were hypersensitive to environmental stresses, including elevated temperature and increased osmolarity. In these D-MEKK1 mutants, activation of Drosophila p38 MAPK in response to stress was poor compared with activation in wild-type animals. These results suggest that D-MEKK1 regulation of the p38 MAPK pathway is critical for the response to environmental stresses in Drosophila.