A Drosophila IkappaB kinase complex required for Relish cleavage and antibacterial immunity.
Here we report the identification of a Drosophila IkappaB kinase complex containing DmIKKbeta and DmIKKgamma, homologs of the human IKKbeta and IKKgamma proteins. We show that this complex is required for the signal-dependent cleavage of Relish, a member of the Rel family of transcriptional activator proteins, and for the activation of antibacterial immune response genes. In addition, we find that the activated DmIKK complex, as well as recombinant DmIKKbeta, can phosphorylate Relish in vitro. Thus, we propose that the Drosophila IkappaB kinase complex functions, at least in part, by inducing the proteolytic cleavage of Relish. The N terminus of Relish then translocates to the nucleus and activates the transcription of antibacterial immune response genes. Remarkably, this Drosophila IkappaB kinase complex is not required for the activation of the Rel proteins Dif and Dorsal through the Toll signaling pathway, which is essential for antifungal immunity and dorsoventral patterning during early development. Thus, a yet to be identified IkappaB kinase complex must be required for Rel protein activation via the Toll signaling pathway.
Silverman
N
N
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Zhou
R
R
Stöven
S
S
Pandey
N
N
Hultmark
D
D
Maniatis
T
T
D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000276:immunology*; D005786:Gene Expression Regulation; D017344:Genes, Insect; D051550:I-kappa B Kinase; D019476:Insect Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021382:Protein Sorting Signals; D021122:Protein Subunits; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000378:metabolism*
D000890:Anti-Infective Agents; D029721:Drosophila Proteins; D019476:Insect Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010455:Peptides; D021382:Protein Sorting Signals; D021122:Protein Subunits; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; C101626:Rel protein, Drosophila; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; C496563:IKKbeta protein, Drosophila