%0 Figure %A Xu, Xiaowen %A Li, Meifeng %A Wu, Chuxin %A Li, Dongming %A Jiang, Zeyin %A Liu, Changxin %A Cheng, Bo %A Mao, Huiling %A Hu, Chengyu %D 2019 %T Image_1_The Fish-Specific Protein Kinase (PKZ) Initiates Innate Immune Responses via IRF3- and ISGF3-Like Mediated Pathways.TIF %U https://frontiersin.figshare.com/articles/figure/Image_1_The_Fish-Specific_Protein_Kinase_PKZ_Initiates_Innate_Immune_Responses_via_IRF3-_and_ISGF3-Like_Mediated_Pathways_TIF/7905905 %R 10.3389/fimmu.2019.00582.s001 %2 https://frontiersin.figshare.com/ndownloader/files/14726696 %K PKZ %K PRR %K IRF3-mediated and ISGF3-like mediated pathways %K innate immunity %K teleost %X

PKZ is a fish-specific protein kinase containing Zα domains. PKZ is known to induce apoptosis through phosphorylating eukaryotic initiation factor 2α kinase (eIF2α) in the same way as double-stranded RNA-dependent protein kinase (PKR), but its exact role in detecting pathogens remains to be fully elucidated. Herein, we have found that PKZ acts as a fish-specific DNA sensor by initiating IFN expression through IRF3- or ISGF3-like mediated pathways. The expression pattern of PKZ is similar to those of innate immunity mediators stimulated by poly (dA:dT) and poly (dG:dC). DNA-PKZ interaction can enhance PKZ phosphorylation and dimerization in vitro. These findings indicate that PKZ participates in cytoplasmic DNA-mediated signaling. Subcellular localization assays have also shown that PKZ is located in the cytoplasm, which suggests that PKZ acts as a cytoplasmic PRR. Meanwhile, co-IP assays have shown that PKZ can separately interact with IRF3, STING, ZDHHC1, eIF2α, IRF9, and STAT2. Further investigations have revealed that PKZ can activate IRF3 and STAT2; and that IRF3-dependent and ISGF3-like dependent mediators are critical for PKZ-induced IFN expression. These results demonstrate that PKZ acts as a special DNA pattern-recognition receptor, and that PKZ can trigger immune responses through IRF3-mediated or ISGF3-like mediated pathways in fish.

%I Frontiers