Grass carp (Ctenopharyngodon idellus) SHP2 suppresses IFN I expression via decreasing the phosphorylation of GSK3β in a non-contact manner
| Autor: | Shina Lu, Kaile Chang, Yapeng Liu, Xiaojue Peng, Hailing Du, Gang Lin, Hang Deng, Xiaowen Xu, Yangfeng Lv, Weihua Qiu, Shanghong Wang, Chengyu Hu, Kang Xu |
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| Rok vydání: | 2020 |
| Předmět: |
Fish Proteins
Carps Protein Tyrosine Phosphatase Non-Receptor Type 11 Protein tyrosine phosphatase Aquatic Science Biology Homology (biology) Cell Line Environmental Chemistry Animals Amino Acid Sequence Phosphorylation Gene Phylogeny chemistry.chemical_classification Glycogen Synthase Kinase 3 beta General Medicine biology.organism_classification Grass carp Amino acid Cell biology Poly I-C chemistry Cytoplasm Interferon Type I Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Fishshellfish immunology. 116 |
| ISSN: | 1095-9947 |
| Popis: | As a tyrosine phosphatase, Src homology 2-containing protein tyrosine phosphatase 2 (SHP2) serves as an inhibitor in PI3K-Akt pathway. In mammals, SHP2 can phosphorylate GSK3β at Y216 site to control the expression of IFN. So far, the multiple functions of SHP2 have been reported in mammals. However, little is known about fish SHP2. In this study, we cloned and identified a grass carp (Ctenopharyngodon idellus) SHP2 gene (CiSHP2, MT373151). SHP2 is conserved among different vertebrates by amino acid sequences alignment and the phylogenetic tree analysis. CiSHP2 shared the closest homology with Danio rerio SHP2. Simultaneously, SHP2 was also tested in grass carp tissues and CIK (C. idellus kidney) cells. We found that it responded to poly I:C stimulation. CiSHP2 was located in the cytoplasm just as the same as those of mammals. Interestingly, it inhibited the phosphorylation level of GSK3β in a non-contact manner. Meanwhile CiGSK3β interacted with and directly phosphorylated CiTBK1. In addition, we found that CiSHP2 also reduced the phosphorylation level of CiTBK1 by CiGSK3β, and then it depressed the expression of IFN I via GSK3β-TBK1 axis. These results suggested that CiSHP2 was involved in CiGSK3β and CiTBK1 activity but not regulated their transcriptional level. At the same time, we also found that CiSHP2 also influenced the activity of CiIRF3. Therefore, fish SHP2 inhibited IFN I expression through blocking GSK3β-TBK1 signal axis. |
| Databáze: | OpenAIRE |
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