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...
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Published in | Frontiers in immunology Vol. 12; p. 780667 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
26.11.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Tiehui Wang, University of Aberdeen, United Kingdom This article was submitted to Comparative Immunology, a section of the journal Frontiers in Immunology Reviewed by: Xinhua Chen, Fujian Agriculture and Forestry University, China; Chengyu Hu, Nanchang University, China |
ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2021.780667 |