title: The Atlantic salmon protein tyrosine kinase Tyk2: molecular cloning, modulation of expression and function.
abstract: Tyk2, a member of the Janus Kinase (JAK) family of protein tyrosine kinases, is required for interferon-α/β binding and signaling in higher vertebrates. Currently, little is known about the role of the different JAKs in signaling responses to interferon (IFN) in lower vertebrates including fish. In this paper we report the identification and characterization of Atlantic salmon (Salmo salar) Tyk2. Four cDNA sequences, two containing an open reading frame encoding full-length Tyk protein and two with an up-stream in frame stop codon, were identified. The deduced amino acid sequences of the salmon full-length Tyk2 proteins showed highest identity with Tyk2 from other species and their transcripts were ubiquitously expressed. Like in mammals the presented data suggests that salmon Tyk2 is auto-phosporylated when ectopically expressed in cells. In our experiments, full-length salmon Tyk2 overexpressed in CHSE-cells phosphorylated itself, while both a kinase-deficient mutant and the truncated Tyk2 (Tyk-short) were inactive. Interestingly, the overexpression of full length Tyk2 was shown to up-regulate the transcript levels of the IFN induced gene Mx, thus indicating the involvement of salmon Tyk2 in the salmon IFN I pathway.
authors.affiliation: Norwegian College of Fisheries Science, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Sobhkhez
authors.forename: Tom
authors.initials: T
authors.lastname: Hansen
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Iliev
authors.forename: Astrid
authors.initials: A
authors.lastname: Skjesol
authors.forename: Jorunn B
authors.initials: JB
authors.lastname: Jørgensen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods; D018076:DNA, Complementary / Q000235:genetics; D029941:Fish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007372:Interferons / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010802:Phylogeny; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D020317:Salmo salar / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018076:DNA, Complementary; D029941:Fish Proteins; D007372:Interferons; D011505:Protein-Tyrosine Kinases; D053634:TYK2 Kinase
keywords: HK; IFN; ISG’s; ISRE; Innate immunity; Interferon; Interferons; JAK; JH; Janus kinase; STAT; Salmo salar; Tyk2; Tyrosine kinase 2; Tyrosine kinase 2 (Tyk2); aa; amino acid; base pair; bp; head kidney; interferon responsive genes; interferon stimulated response element; janus homology; signal transducers and activators of the transcription; ss