In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-11-26)
Abstract:
Src homology region 2 domain-containing phosphatase 1 (SHP1), encoded by the protein tyrosine phosphatase nonreceptor type 6 ( ptpn6 ) 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 ( Carassius gibelio ) ptpn6 homeologs ( Cgptpn6-A and Cgptpn6-B ), each of which had three alleles with high identities. Then, relative to Cgptpn6-B , dominant expression in adult tissues and higher upregulated expression of Cgptpn6-A 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 Cg SHP1-A (encoded by the Cgptpn6-A gene) and Cg SHP1-B (encoded by the Cgptpn6-B gene) act as negative regulators of the RIG-I-like receptor (RLR)-mediated interferon (IFN) response via two mechanisms: the inhibition of Ca TBK1-induced phosphorylation of Ca MITA shared by Cg SHP1-A and Cg SHP1-B, and the autophagic degradation of Ca MITA exclusively by Cg SHP1-A. Meanwhile, the data support that Cg SHP1-A and Cg SHP1-B have sub-functionalized and that Cg SHP1-A overwhelmingly dominates Cg 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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.780667
DOI:
10.3389/fimmu.2021.780667.s001
DOI:
10.3389/fimmu.2021.780667.s002
DOI:
10.3389/fimmu.2021.780667.s003
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2606827-8
