PMID- 34265416 OWN - NLM STAT- MEDLINE DCOM- 20210826 LR - 20210826 IS - 1095-9947 (Electronic) IS - 1050-4648 (Linking) VI - 116 DP - 2021 Sep TI - Grass carp (Ctenopharyngodon idellus) SHP2 suppresses IFN I expression via decreasing the phosphorylation of GSK3beta in a non-contact manner. PG - 150-160 LID - S1050-4648(21)00194-7 [pii] LID - 10.1016/j.fsi.2021.07.005 [doi] AB - 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 GSK3beta 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 GSK3beta in a non-contact manner. Meanwhile CiGSK3beta interacted with and directly phosphorylated CiTBK1. In addition, we found that CiSHP2 also reduced the phosphorylation level of CiTBK1 by CiGSK3beta, and then it depressed the expression of IFN I via GSK3beta-TBK1 axis. These results suggested that CiSHP2 was involved in CiGSK3beta 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 GSK3beta-TBK1 signal axis. CI - Copyright (c) 2021. Published by Elsevier Ltd. FAU - Lu, Shina AU - Lu S AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Peng, Xiaojue AU - Peng X AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Lin, Gang AU - Lin G AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Xu, Kang AU - Xu K AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Wang, Shanghong AU - Wang S AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Qiu, Weihua AU - Qiu W AD - Teaching Material Research Office of Jiangxi Provincial Education Department, Nanchang, 330046, Jiangxi, China. FAU - Du, Hailing AU - Du H AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Chang, Kaile AU - Chang K AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Lv, Yangfeng AU - Lv Y AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Liu, Yapeng AU - Liu Y AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Deng, Hang AU - Deng H AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Hu, Chengyu AU - Hu C AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. FAU - Xu, Xiaowen AU - Xu X AD - School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China. Electronic address: xuxw2020@163.com. LA - eng PT - Journal Article DEP - 20210712 PL - England TA - Fish Shellfish Immunol JT - Fish & shellfish immunology JID - 9505220 RN - 0 (Fish Proteins) RN - 0 (Interferon Type I) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) RN - O84C90HH2L (Poly I-C) SB - IM MH - Amino Acid Sequence MH - Animals MH - Carps/genetics/*immunology MH - Cell Line MH - Fish Proteins/genetics/*immunology MH - Glycogen Synthase Kinase 3 beta/*immunology MH - Interferon Type I/*immunology MH - Phosphorylation MH - Phylogeny MH - Poly I-C/pharmacology MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/*immunology OTO - NOTNLM OT - Fish OT - GSK3beta-TBK1 axis OT - Innate immune OT - Phosphorylation OT - SHP2 EDAT- 2021/07/16 06:00 MHDA- 2021/08/27 06:00 CRDT- 2021/07/15 20:16 PHST- 2020/12/16 00:00 [received] PHST- 2021/07/05 00:00 [revised] PHST- 2021/07/11 00:00 [accepted] PHST- 2021/07/16 06:00 [pubmed] PHST- 2021/08/27 06:00 [medline] PHST- 2021/07/15 20:16 [entrez] AID - S1050-4648(21)00194-7 [pii] AID - 10.1016/j.fsi.2021.07.005 [doi] PST - ppublish SO - Fish Shellfish Immunol. 2021 Sep;116:150-160. doi: 10.1016/j.fsi.2021.07.005. Epub 2021 Jul 12.