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EMBO J. 2001 Oct 1;20(19):5421-30.

A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK.

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  • 1Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan.

Abstract

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.

PMID:
11574474
PMCID:
PMC125648
DOI:
10.1093/emboj/20.19.5421
[PubMed - indexed for MEDLINE]
Free PMC Article
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