A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK.
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.
Inoue
H
H
Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya 464-8602, Japan.
Tateno
M
M
Fujimura-Kamada
K
K
Takaesu
G
G
Adachi-Yamada
T
T
Ninomiya-Tsuji
J
J
Irie
K
K
Nishida
Y
Y
Matsumoto
K
K
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
D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases