TYK2 kinase activity is required for functional type I interferon responses in vivo.
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 k...
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2012
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oai:doaj.org-article:81f359711dbb4b4190faa0129dca17de2021-11-18T07:15:09ZTYK2 kinase activity is required for functional type I interferon responses in vivo.1932-620310.1371/journal.pone.0039141https://doaj.org/article/81f359711dbb4b4190faa0129dca17de2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723949/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Tyrosine 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 (Tyk2(K923E)) 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 TYK2(K923E)in vitro. Tyk2(K923E) 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.Michaela Prchal-MurphyChristian SemperCaroline LassnigBarbara WallnerChristian GaustererIngeborg Teppner-KlymiukJulianna KobolakSimone MüllerThomas KolbeMarina KaraghiosoffAndras DinnyésThomas RülickeNicole R LeitnerBirgit StroblMathias MüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39141 (2012) |
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DOAJ |
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EN |
| topic |
Medicine R Science Q |
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Medicine R Science Q Michaela Prchal-Murphy Christian Semper Caroline Lassnig Barbara Wallner Christian Gausterer Ingeborg Teppner-Klymiuk Julianna Kobolak Simone Müller Thomas Kolbe Marina Karaghiosoff Andras Dinnyés Thomas Rülicke Nicole R Leitner Birgit Strobl Mathias Müller TYK2 kinase activity is required for functional type I interferon responses in vivo. |
| description |
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 (Tyk2(K923E)) 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 TYK2(K923E)in vitro. Tyk2(K923E) 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. |
| format |
article |
| author |
Michaela Prchal-Murphy Christian Semper Caroline Lassnig Barbara Wallner Christian Gausterer Ingeborg Teppner-Klymiuk Julianna Kobolak Simone Müller Thomas Kolbe Marina Karaghiosoff Andras Dinnyés Thomas Rülicke Nicole R Leitner Birgit Strobl Mathias Müller |
| author_facet |
Michaela Prchal-Murphy Christian Semper Caroline Lassnig Barbara Wallner Christian Gausterer Ingeborg Teppner-Klymiuk Julianna Kobolak Simone Müller Thomas Kolbe Marina Karaghiosoff Andras Dinnyés Thomas Rülicke Nicole R Leitner Birgit Strobl Mathias Müller |
| author_sort |
Michaela Prchal-Murphy |
| title |
TYK2 kinase activity is required for functional type I interferon responses in vivo. |
| title_short |
TYK2 kinase activity is required for functional type I interferon responses in vivo. |
| title_full |
TYK2 kinase activity is required for functional type I interferon responses in vivo. |
| title_fullStr |
TYK2 kinase activity is required for functional type I interferon responses in vivo. |
| title_full_unstemmed |
TYK2 kinase activity is required for functional type I interferon responses in vivo. |
| title_sort |
tyk2 kinase activity is required for functional type i interferon responses in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/81f359711dbb4b4190faa0129dca17de |
| work_keys_str_mv |
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