Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals

Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

Astrid Skjesol, Theresa Liebe, Dimitar B Iliev, Ernst I S Thomassen, Linn Greiner Tollersrud, Mehrdad Sobhkhez, Lisbeth Lindenskov Joensen, Christopher J Secombes, Jorunn B Jørgensen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.

Original languageEnglish
Pages (from-to)177-189
Number of pages13
JournalDevelopmental and Comparative Immunology
Volume45
Issue number1
Early online date28 Feb 2014
DOIs
Publication statusPublished - Jul 2014

Fingerprint

Suppressor of Cytokine Signaling Proteins
Salmo salar
Interferon Type I
Interferons
Interferon-gamma
Mammals
Fishes
Zebrafish
Cytokines
Aptitude
Salmon
Genes
Vertebrates
Phosphotransferases

Keywords

  • SOCS
  • JAK/STAT signaling
  • interferons
  • Atlantic salmon

Cite this

Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals : Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling. / Skjesol, Astrid; Liebe, Theresa; Iliev, Dimitar B; Thomassen, Ernst I S; Tollersrud, Linn Greiner; Sobhkhez, Mehrdad; Lindenskov Joensen, Lisbeth; Secombes, Christopher J; Jørgensen, Jorunn B.

In: Developmental and Comparative Immunology, Vol. 45, No. 1, 07.2014, p. 177-189.

Research output: Contribution to journalArticle

Skjesol, Astrid ; Liebe, Theresa ; Iliev, Dimitar B ; Thomassen, Ernst I S ; Tollersrud, Linn Greiner ; Sobhkhez, Mehrdad ; Lindenskov Joensen, Lisbeth ; Secombes, Christopher J ; Jørgensen, Jorunn B. / Functional conservation of suppressors of cytokine signaling proteins between teleosts and mammals : Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling. In: Developmental and Comparative Immunology. 2014 ; Vol. 45, No. 1. pp. 177-189.
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T2 - Atlantic salmon SOCS1 binds to JAK/STAT family members and suppresses type I and II IFN signaling

AU - Skjesol, Astrid

AU - Liebe, Theresa

AU - Iliev, Dimitar B

AU - Thomassen, Ernst I S

AU - Tollersrud, Linn Greiner

AU - Sobhkhez, Mehrdad

AU - Lindenskov Joensen, Lisbeth

AU - Secombes, Christopher J

AU - Jørgensen, Jorunn B

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/7

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N2 - Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.

AB - Suppressor of cytokine signaling (SOCS) proteins are crucially involved in the control of inflammatory responses through their impact on various signaling pathways including the JAK/STAT pathway. Although all SOCS protein family members are identified in teleost fish, their functional properties in non-mammalian vertebrates have not been extensively studied. To gain further insight into SOCS functions in bony fish, we have identified and characterized the Atlantic salmon (Salmo salar) SOCS1, SOCS2 and CISH genes. These genes exhibited sequence conservation with their mammalian counterparts and they were ubiquitously expressed. SOCS1 in mammalian species has been recognized as a key negative regulator of interferon (IFN) signaling and recent data for the two model fish Tetraodon (Tetraodon nigroviridis) and zebrafish (Danio rerio) suggest that these functions are conserved from teleost to mammals. In agreement with this we here demonstrate a strong negative regulatory activity of salmon SOCS1 on type I and type II IFN signaling, while SOCS2a and b and CISH only moderately affected IFN responses. SOCS1 also inhibited IFNγ-induced nuclear localization of STAT1 and a direct interaction between SOCS1 and STAT1 and between SOCS1 and the Tyk2 kinase was found. Using SOCS1 mutants lacking either the KIR domain or the ESS, SH2 and SOCS box domains showed that all domains affected the ability of SOCS1 to inhibit IFN-mediated signaling. These results are the first to demonstrate that SOCS1 is a potent inhibitor of IFN-mediated JAK-STAT signaling in teleost fish.

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KW - JAK/STAT signaling

KW - interferons

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