Immune activation of NF-κB and JNK requires Drosophila TAK1

被引:216
作者
Silverman, N
Zhou, R
Erlich, RL
Hunter, M
Bernstein, E
Schneider, D
Maniatis, T
机构
[1] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA
[2] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
[3] Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA
[4] MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA
[5] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
关键词
D O I
10.1074/jbc.M304802200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:48928 / 48934
页数:7
相关论文
共 46 条
[41]   TAK1 is critical for IκB kinase-mediated activation of the NF-κB pathway [J].
Takaesu, G ;
Surabhi, RM ;
Park, KJ ;
Ninomiya-Tsuji, J ;
Matsumoto, K ;
Gaynor, RB .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 326 (01) :105-115
[42]  
TOWNSEND JP, 1982, GENOME BIOL
[43]   How Drosophila combats microbial infection:: a model to study innate immunity and host-pathogen interactions [J].
Tzou, P ;
De Gregorio, E ;
Lemaitre, B .
CURRENT OPINION IN MICROBIOLOGY, 2002, 5 (01) :102-110
[44]   Mutations in the Drosophila dTAK1 gene reveal a conserved function or MAPKKKs in the control of rel/NF-κB-dependent innate immune responses [J].
Vidal, S ;
Khush, RS ;
Leulier, F ;
Tzou, P ;
Nakamura, M ;
Lemaitre, B .
GENES & DEVELOPMENT, 2001, 15 (15) :1900-1912
[45]   TAK1 is a ubiquitin-dependent kinase of MKK and IKK [J].
Wang, C ;
Deng, L ;
Hong, M ;
Akkaraju, GR ;
Inoue, J ;
Chen, ZJJ .
NATURE, 2001, 412 (6844) :346-351
[46]   Regulation of TNF expression by multiple mitogen-activated protein kinase pathways [J].
Zhu, W ;
Downey, JS ;
Gu, J ;
Di Padova, F ;
Gram, H ;
Han, JH .
JOURNAL OF IMMUNOLOGY, 2000, 164 (12) :6349-6358