D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells.
BACKGROUND
The family of c-Jun NH2-terminal kinases (JNK) plays important roles in embryonic development and in cellular responses to stress. Toxic metals and their compounds are potent activators of JNK in mammalian cells. The mechanism of mammalian JNK activation by cadmium and sodium arsenite involves toxicant-induced oxidative stress. The study of mammalian signaling pathways to JNK is complicated by the significant degree of redundancy among upstream JNK regulators, especially at the level of JNK kinase kinases (JNKKK).


RESULTS
Using Drosophila melanogaster S2 cells, we demonstrate here that cadmium and arsenite activate Drosophila JNK (D-JNK) via oxidative stress as well, thus providing a simpler model system to study JNK signaling. To elucidate the signaling pathways that lead to activation of D-JNK in response to cadmium or arsenite, we employed RNA interference (RNAi) to knock down thirteen upstream regulators of D-JNK, either singly or in combinations of up to seven at a time.


CONCLUSIONS
D-MEKK1, the fly orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediates the activation of D-JNK by cadmium and arsenite.
Ryabinina
Olga P
OP
Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, Oregon 97239, USA. ryabinio@ohsu.edu
Subbian
Ezhilkani
E
Iordanov
Mihail S
MS
D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002104:Cadmium / Q000494:pharmacology*; D002460:Cell Line; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004789:Enzyme Activation; D006430:Hemiptera; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D007700:Kinetics; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism*; D048768:MAP Kinase Kinase Kinase 4 / Q000378:metabolism*; D008322:Mammals; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018053:Arsenites; D029721:Drosophila Proteins; D002104:Cadmium; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D048768:MAP Kinase Kinase Kinase 4; C015001:arsenite