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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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using<jats:italic>Drosophila melanogaster<\/jats:italic>S2 cells, we demonstrate here that cadmium and arsenite activate<jats:italic>Drosophila<\/jats:italic>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>D-MEKK1, the fly orthologue of mammalian MEKK4\/MTK1, and<jats:italic>Hemipterous<\/jats:italic>\/D-MKK7 mediates the activation of D-JNK by cadmium and arsenite.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2121-7-7","type":"journal-article","created":{"date-parts":[[2006,2,4]],"date-time":"2006-02-04T19:16:50Z","timestamp":1139080610000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["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"],"prefix":"10.1186","volume":"7","author":[{"given":"Olga P","family":"Ryabinina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezhilkani","family":"Subbian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihail S","family":"Iordanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,2,1]]},"reference":[{"issue":"3-4","key":"180_CR1","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S0079-6107(98)00056-X","volume":"71","author":"MH Cobb","year":"1999","unstructured":"Cobb MH: MAP kinase pathways. 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