Inoue, H., Tateno, M., Fujimura-Kamada, K., Takaesu, G., Adachi-Yamada, T., Ninomiya-Tsuji, J., Irie, K., Nishida, Y., Matsumoto, K. (2001). A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38 MAPK.  EMBO J. 20(19): 5421--5430.

FBrf0139644

Research paper

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.

PMC125648 (PMC) (EuropePMC)