title: Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila.
abstract: The molecular circuitry underlying innate immunity is constructed of multiple, evolutionarily conserved signaling modules with distinct regulatory targets. The MAP kinases and the IKK-NF-kappa B molecules play important roles in the initiation of immune effector responses. We have found that the Drosophila NF-kappa B protein Relish plays a crucial role in limiting the duration of JNK activation and output in response to Gram-negative infections. Relish activation is linked to proteasomal degradation of TAK1, the upstream MAP kinase kinase kinase required for JNK activation. Degradation of TAK1 leads to a rapid termination of JNK signaling, resulting in a transient JNK-dependent response that precedes the sustained induction of Relish-dependent innate immune loci. Because the IKK-NF-kappa B module also negatively regulates JNK activation in mammals, thereby controlling inflammation-induced apoptosis, the regulatory cross-talk between the JNK and NF-kappa B pathways appears to be broadly conserved.
authors.affiliation: Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, 92093-0636, USA.
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Helen
authors.initials: H
authors.lastname: Brady
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ruocco
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Sun
authors.forename: DeeAnn
authors.initials: D
authors.lastname: Williams
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kato
authors.forename: Normand
authors.initials: N
authors.lastname: Richards
authors.forename: Kyle
authors.initials: K
authors.lastname: Chan
authors.forename: Frank
authors.initials: F
authors.lastname: Mercurio
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wasserman
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology; D010450:Endopeptidases / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000276:immunology; D007109:Immunity / Q000235:genetics*; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B; D020239:Receptor Cross-Talk / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D029721:Drosophila Proteins; D010450:Endopeptidases; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D014157:Transcription Factors; D000099151:MAP Kinase Kinase Kinase 7; C101626:Rel protein, Drosophila