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.