AUTHOR=Tong Jin-Feng , Zhou Li , Li Shun , Lu Long-Feng , Li Zhuo-Cong , Li Zhi , Gan Rui-Hai , Mou Cheng-Yan , Zhang Qi-Ya , Wang Zhong-Wei , Zhang Xiao-Juan , Wang Yang , Gui Jian-Fang 

TITLE=Two Duplicated Ptpn6 Homeologs Cooperatively and Negatively Regulate RLR-Mediated IFN Response in Hexaploid Gibel Carp

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.780667

DOI=10.3389/fimmu.2021.780667

ISSN=1664-3224

ABSTRACT=<p>Src homology region 2 domain-containing phosphatase 1 (SHP1), encoded by the <italic>protein tyrosine phosphatase nonreceptor type 6</italic> (<italic>ptpn6</italic>) gene, belongs to the family of protein tyrosine phosphatases (PTPs) and participates in multiple signaling pathways of immune cells. However, the mechanism of SHP1 in regulating fish immunity is largely unknown. In this study, we first identified two gibel carp (<italic>Carassius gibelio</italic>) <italic>ptpn6</italic> homeologs (<italic>Cgptpn6-A</italic> and <italic>Cgptpn6-B</italic>), each of which had three alleles with high identities. Then, relative to <italic>Cgptpn6-B</italic>, dominant expression in adult tissues and higher upregulated expression of <italic>Cgptpn6-A</italic> induced by polyinosinic-polycytidylic acid (poly I:C), poly deoxyadenylic-deoxythymidylic (dA:dT) acid and spring viremia of carp virus (SVCV) were uncovered. Finally, we demonstrated that <italic>Cg</italic>SHP1-A (encoded by the <italic>Cgptpn6-A</italic> gene) and <italic>Cg</italic>SHP1-B (encoded by the <italic>Cgptpn6-B</italic> gene) act as negative regulators of the RIG-I-like receptor (RLR)-mediated interferon (IFN) response <italic>via</italic> two mechanisms: the inhibition of <italic>Ca</italic>TBK1-induced phosphorylation of <italic>Ca</italic>MITA shared by <italic>Cg</italic>SHP1-A and <italic>Cg</italic>SHP1-B, and the autophagic degradation of <italic>Ca</italic>MITA exclusively by <italic>Cg</italic>SHP1-A. Meanwhile, the data support that <italic>Cg</italic>SHP1-A and <italic>Cg</italic>SHP1-B have sub-functionalized and that <italic>Cg</italic>SHP1-A overwhelmingly dominates <italic>Cg</italic>SHP1-B in the process of RLR-mediated IFN response. The current study not only sheds light on the regulative mechanism of SHP1 in fish immunity, but also provides a typical case of duplicated gene evolutionary fates.</p>