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| The EMBO Journal
(2001) 20, 5421–5430, doi:10.1093/emboj/20.19.5421 |
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| A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK |
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| Hideki Inoue, Minoru Tateno, Konomi Fujimura-Kamada, Giichi Takaesu, Takashi Adachi-Yamada, Jun Ninomiya-Tsuji, Kenji Irie, Yasuyoshi Nishida and Kunihiro Matsumoto |
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Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan To whom correspondence should be addressed Kunihiro Matsumoto, g44177a@nucc.cc.nagoya-u.ac.jp Received 30 April 2001; Revised 8 August 2001; Accepted 8 August 2001. |
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| Abstract |
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| In cultured mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses. How ever, 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. |
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| Keywords: Drosophila, MAPKKK, p38 MAPK, stress responses |
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