TYK2 kinase activity is required for functional type I interferon responses in Vivo

Michaela Prchal-Murphy, Christian Semper, Caroline Lassnig, Barbara Wallner, Christian Gausterer, Ingeborg Teppner-Klymiuk, Julianna Kobolak, Simone Müller, Thomas Kolbe, Marina Karaghiosoff, A. Dinnyés, Thomas Rülicke, Nicole R. Leitner, Birgit Strobl, Mathias Müller

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, i.e., non-canonical, functions. We have generated gene-targeted mice harbouring a mutation in the ATP-binding pocket of the kinase domain. The Tyk2 kinase-inactive (Tyk2K923E) mice are viable and show no gross abnormalities. We show that kinase-active TYK2 is required for full-fledged type I interferon- (IFN) induced activation of the transcription factors STAT1-4 and for the in vivo antiviral defence against viruses primarily controlled through type I IFN actions. In addition, TYK2 kinase activity was found to be required for the protein's stability. An inhibitory function was only observed upon over-expression of TYK2K923E in vitro. Tyk2K923E mice represent the first model for studying the kinase-independent function of a JAK in vivo and for assessing the consequences of side effects of JAK inhibitors.

Original languageEnglish
Article numbere39141
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 18 2012

Fingerprint

TYK2 Kinase
Interferon Type I
interferons
tyrosine
phosphotransferases (kinases)
Phosphotransferases
Janus Kinases
non-specific protein-tyrosine kinase
STAT1 Transcription Factor
Protein Stability
mice
Viruses
Antiviral Agents
Genes
Adenosine Triphosphate
Chemical activation
Cytokines
Mutation
cytokines
transcription factors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Prchal-Murphy, M., Semper, C., Lassnig, C., Wallner, B., Gausterer, C., Teppner-Klymiuk, I., ... Müller, M. (2012). TYK2 kinase activity is required for functional type I interferon responses in Vivo. PLoS One, 7(6), [e39141]. https://doi.org/10.1371/journal.pone.0039141

TYK2 kinase activity is required for functional type I interferon responses in Vivo. / Prchal-Murphy, Michaela; Semper, Christian; Lassnig, Caroline; Wallner, Barbara; Gausterer, Christian; Teppner-Klymiuk, Ingeborg; Kobolak, Julianna; Müller, Simone; Kolbe, Thomas; Karaghiosoff, Marina; Dinnyés, A.; Rülicke, Thomas; Leitner, Nicole R.; Strobl, Birgit; Müller, Mathias.

In: PLoS One, Vol. 7, No. 6, e39141, 18.06.2012.

Research output: Contribution to journalArticle

Prchal-Murphy, M, Semper, C, Lassnig, C, Wallner, B, Gausterer, C, Teppner-Klymiuk, I, Kobolak, J, Müller, S, Kolbe, T, Karaghiosoff, M, Dinnyés, A, Rülicke, T, Leitner, NR, Strobl, B & Müller, M 2012, 'TYK2 kinase activity is required for functional type I interferon responses in Vivo', PLoS One, vol. 7, no. 6, e39141. https://doi.org/10.1371/journal.pone.0039141
Prchal-Murphy M, Semper C, Lassnig C, Wallner B, Gausterer C, Teppner-Klymiuk I et al. TYK2 kinase activity is required for functional type I interferon responses in Vivo. PLoS One. 2012 Jun 18;7(6). e39141. https://doi.org/10.1371/journal.pone.0039141
Prchal-Murphy, Michaela ; Semper, Christian ; Lassnig, Caroline ; Wallner, Barbara ; Gausterer, Christian ; Teppner-Klymiuk, Ingeborg ; Kobolak, Julianna ; Müller, Simone ; Kolbe, Thomas ; Karaghiosoff, Marina ; Dinnyés, A. ; Rülicke, Thomas ; Leitner, Nicole R. ; Strobl, Birgit ; Müller, Mathias. / TYK2 kinase activity is required for functional type I interferon responses in Vivo. In: PLoS One. 2012 ; Vol. 7, No. 6.
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