A Drosophila IκB kinase complex required for Relish cleavage and antibacterial immunity

Here we report the identification of a Drosophila I kappa B kinase complex containing DmIKK beta and DmIKK gamma, homologs of the human IKK beta and IKK gamma 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 DmIKK beta, can phosphorylate Relish in vitro. Thus, we propose that the Drosophila I kappa B 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 I kappa B 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 I kappa B kinase complex must be required for Rel protein activation via the Toll signaling pathway.