Silverman Neal, Zhou Rui, Erlich Rachel L, Hunter Mike, Bernstein Erik, Schneider David, Maniatis Tom
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
J Biol Chem. 2003 Dec 5;278(49):48928-34. doi: 10.1074/jbc.M304802200. Epub 2003 Sep 30.
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.
对果蝇免疫反应的刺激会激活核因子κB（NF-κB）和应激活化蛋白激酶（JNK）信号通路。例如，革兰氏阴性菌感染会诱导免疫缺陷（Imd）信号通路，导致类NF-κB转录因子Relish的激活以及一系列编码抗菌肽的基因的表达。细菌感染也会激活JNK通路，但该通路在免疫反应中的作用尚未明确。遗传学实验表明，哺乳动物丝裂原活化蛋白激酶激酶激酶（MAPK激酶激酶）TAK1（转化生长因子β激活激酶1）的果蝇同源物在免疫刺激后会激活JNK和NF-κB通路。在本报告中，我们证明果蝇TAK1既作为果蝇IκB激酶激活激酶，又作为JNK激酶激活激酶发挥作用。然而，我们发现抗菌肽基因表达并不需要JNK信号，但激活包括Punch、硫酸化和malvolio在内的其他免疫诱导基因则需要JNK信号。因此，JNK信号似乎在细胞免疫反应和应激反应中发挥重要作用。
