The Drosophila proteins Pelle and Tube induce JNK/AP-1 activity in mammalian cells.
The mammalian interleukin-1 (IL-1) signal transduction pathways display remarkable homology to the Toll signaling cascade in Drosophila. To address the question whether members of the Drosophila Toll pathway are functional in mammalian cells, inactive and constitutively active versions of the protein kinase Pelle and its regulator Tube were expressed in HeLa cells and tested for their impact on IL-1-dependent signaling events. The Drosophila proteins failed to induce the IL-1-responsive transcription factor, nuclear factor-kappaB, but selectively activated the IL-1-regulated kinase, c-Jun N-terminal 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, showing the functionality of the Drosophila proteins in mammalian cells.
Bacher
S
S
German Cancer Research Center, Department of Immunochemistry (G0200), Heidelberg, Germany.
Grosshans
J
J
Dröge
W
W
Schmitz
M L
ML
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D017930:Genes, Reporter; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019476:Insect Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D053592:Interleukin-1 Receptor-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D011971:Receptors, Immunologic; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D029721:Drosophila Proteins; D019476:Insect Proteins; D007375:Interleukin-1; C507779:MYD88 protein, human; C499312:Myd88 protein, Drosophila; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011971:Receptors, Immunologic; D018808:Transcription Factor AP-1; C084727:tub protein, Drosophila; D011494:Protein Kinases; C079896:pll protein, Drosophila; D053592:Interleukin-1 Receptor-Associated Kinases; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases