The Drosophila proteins Pelle and Tube induce JNK/AP-1 activity in mammalian cells

The mammalian interleukin-1 (IL-1) signal transduction pathways display rem arkable homology to the Toll signaling cascade in Drosophila. To address th e question whether members of the Drosophila Toll pathway are functional in mammalian cells, inactive and constitutively active versions of tile prote in kinase Pelle and its regulator Tube were expressed in HeLa cells and tes ted for their impact on IL-1-dependent signaling events. The Drosophila pro teins failed to induce the IL-1-responsive transcription factor, nuclear fa ctor-kappaB, but selectively activated the IL-1-regulated kinase, c-Jun N-t erminal kinase (JNK), thus resulting in elevated AP-1 activity. Activation of JNK/AP-1 activity was seen upon expression of a Pelle mutant lacking its C-terminal half or by a membrane-bound and multimerised Tube protein, show ing tile functionality of the Drosophila proteins in mammalian cells. (C) 2 001 Federation of European Biochemical Societies, Published bg Elsevier Sci ence B.V. All rights reserved.