Delaney Joseph R, Stöven Svenja, Uvell Hanna, Anderson Kathryn V, Engström Ylva, Mlodzik Marek
Brookdale Department of Developmental, Cell and Molecular Biology, The Mount Sinai School of Medicine, New York, NY, USA.
EMBO J. 2006 Jul 12;25(13):3068-77. doi: 10.1038/sj.emboj.7601182. Epub 2006 Jun 8.
Jun N-terminal kinase (JNK) signaling is a highly conserved pathway that controls both cytoskeletal remodeling and transcriptional regulation in response to a wide variety of signals. Despite the importance of JNK in the mammalian immune response, and various suggestions of its importance in Drosophila immunity, the actual contribution of JNK signaling in the Drosophila immune response has been unclear. Drosophila TAK1 has been implicated in the NF-kappaB/Relish-mediated activation of antimicrobial peptide genes. However, we demonstrate that Relish activation is intact in dTAK1 mutant animals, and that the immune response in these mutant animals was rescued by overexpression of a downstream JNKK. The expression of a JNK inhibitor and induction of JNK loss-of-function clones in immune responsive tissue revealed a general requirement for JNK signaling in the expression of antimicrobial peptides. Our data indicate that dTAK1 is not required for Relish activation, but instead is required in JNK signaling for antimicrobial peptide gene expression.
JNK信号通路是一条高度保守的信号途径，它能够响应多种信号，从而控制细胞骨架重塑和转录调控。尽管JNK在哺乳动物免疫反应中具有重要作用，并且有多种观点认为其在果蝇免疫中也很重要，但JNK信号在果蝇免疫反应中的实际作用仍不明确。果蝇TAK1已被证明与NF-κB/Relish介导的抗菌肽基因激活有关。然而，我们发现Relish激活在dTAK1突变动物中是完整的，并且这些突变动物的免疫反应可通过过表达下游JNKK来挽救。在免疫反应组织中表达JNK抑制剂并诱导JNK功能缺失克隆，结果表明抗菌肽表达普遍需要JNK信号。我们的数据表明，Relish激活不需要dTAK1，但抗菌肽基因表达的JNK信号需要dTAK1。
