title: 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.
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.
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Astrid
authors.initials: A
authors.lastname: Skjesol
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway; Center for Molecular Biomedicine (CMB), Dept. of Biochemistry, University of Jena, D-07745 Jena, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Liebe
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Iliev
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Ernst I S
authors.initials: EI
authors.lastname: Thomassen
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Linn Greiner
authors.initials: LG
authors.lastname: Tollersrud
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Sobhkhez
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Lindenskov Joensen
authors.affiliation: Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Secombes
authors.affiliation: The Norwegian College of Fishery Science, UiT The Arctic University of Norway, N-9037 Tromsø, Norway. Electronic address: jorunn.jorgensen@uit.no.
authors.forename: Jorunn B
authors.initials: JB
authors.lastname: Jørgensen
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism; D009928:Organ Specificity; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism; D020317:Salmo salar; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D029941:Fish Proteins; D007370:Interferon Type I; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D053612:Janus Kinases
keywords: Atlantic salmon; Interferons; JAK/STAT signaling; SOCS