title: A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK.
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.
authors.affiliation: Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Tateno
authors.forename: K
authors.initials: K
authors.lastname: Fujimura-Kamada
authors.forename: G
authors.initials: G
authors.lastname: Takaesu
authors.forename: T
authors.initials: T
authors.lastname: Adachi-Yamada
authors.forename: J
authors.initials: J
authors.lastname: Ninomiya-Tsuji
authors.forename: K
authors.initials: K
authors.lastname: Irie
authors.forename: Y
authors.initials: Y
authors.lastname: Nishida
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila / Q000201:enzymology*; D004777:Environment; D004789:Enzyme Activation; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases