title: Tyrosine kinase 2 - Surveillant of tumours and bona fide oncogene.
abstract: Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which transduces cytokine and growth factor signalling. Analysis of TYK2 loss-of-function revealed its important role in immunity to infection, (auto-) immunity and (auto-) inflammation. TYK2-deficient patients unravelled high similarity between mice and men with respect to cellular signalling functions and basic immunology. Genome-wide association studies link TYK2 to several autoimmune and inflammatory diseases as well as carcinogenesis. Due to its cytokine signalling functions TYK2 was found to be essential in tumour surveillance. Lately TYK2 activating mutants and fusion proteins were detected in patients diagnosed with leukaemic diseases suggesting that TYK2 is a potent oncogene. Here we review the cell intrinsic and extrinsic functions of TYK2 in the characteristics preventing and enabling carcinogenesis. In addition we describe an unexpected function of kinase-inactive TYK2 in tumour rejection.
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Leitner
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Witalisz-Siepracka
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Strobl
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria. Electronic address: mathias.mueller@vetmeduni.ac.at.
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
mesh_terms: D000818:Animals; D055106:Genome-Wide Association Study; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D009857:Oncogenes / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D053634:TYK2 Kinase / Q000235:genetics / Q000276:immunology*
chemical_list: D009363:Neoplasm Proteins; D053634:TYK2 Kinase; C070139:TYK2 protein, human
keywords: Cytokine signalling; Hallmarks of cancer; JAK-STAT pathway; Non-receptor tyrosine kinases