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

Src homology region 2 domain-containing phosphatase 1 (SHP1), encoded by the () 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 () homeologs ( and ), each of which had three alleles with high identities. Then, relative to , dominant expression in adult tissues and higher upregulated expression of 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 SHP1-A (encoded by the gene) and SHP1-B (encoded by the gene) act as negative regulators of the RIG-I-like receptor (RLR)-mediated interferon (IFN) response two mechanisms: the inhibition of TBK1-induced phosphorylation of MITA shared by SHP1-A and SHP1-B, and the autophagic degradation of MITA exclusively by SHP1-A. Meanwhile, the data support that SHP1-A and SHP1-B have sub-functionalized and that SHP1-A overwhelmingly dominates 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.