10.3389/fimmu.2019.00582.s001 Xiaowen Xu Xiaowen Xu Meifeng Li Meifeng Li Chuxin Wu Chuxin Wu Dongming Li Dongming Li Zeyin Jiang Zeyin Jiang Changxin Liu Changxin Liu Bo Cheng Bo Cheng Huiling Mao Huiling Mao Chengyu Hu Chengyu Hu Image_1_The Fish-Specific Protein Kinase (PKZ) Initiates Innate Immune Responses via IRF3- and ISGF3-Like Mediated Pathways.TIF Frontiers 2019 PKZ PRR IRF3-mediated and ISGF3-like mediated pathways innate immunity teleost 2019-03-28 04:21:30 Figure 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 <p>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.</p>