Immune activation of NF-kappaB and JNK requires Drosophila TAK1

Neal S. Silverman, University of Massachusetts Medical School
Rui Zhou
Rachel L. Erlich
Mike Hunter
Erik Bernstein
David S. Schneider
Tom Maniatis

Abstract

Stimulation of the Drosophila immune response activates NF-kappaB and JNK signaling pathways. For example, infection by Gram-negative bacteria induces the Imd signaling pathway, leading to the activation of the NF-kappaB-like transcription factor Relish and the expression of a battery of genes encoding antimicrobial peptides. Bacterial infection also activates the JNK pathway, but the role of this pathway in the immune response has not yet been established. Genetic experiments suggest that the Drosophila homolog of the mammalian MAPK kinase kinase, TAK1 (transforming growth factor beta-activated kinase 1), activates both the JNK and NF-kappaB pathways following immune stimulation. In this report, we demonstrate that Drosophila TAK1 functions as both the Drosophila IkappaB kinase-activating kinase and the JNK kinase-activating kinase. However, we found that JNK signaling is not required for antimicrobial peptide gene expression but is required for the activation of other immune inducible genes, including Punch, sulfated, and malvolio. Thus, JNK signaling appears to play an important role in the cellular immune response and the stress response.