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

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Title: TYK2 kinase activity is required for functional type I interferon responses in vivo.
Authors: 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
Source: PLoS ONE, Vol 7, Iss 6, p e39141 (2012)
Publisher Information: Public Library of Science (PLoS), 2012.
Publication Year: 2012
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723949/pdf/?tool=EBI; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0039141
Access URL: https://doaj.org/article/81f359711dbb4b4190faa0129dca17de
Accession Number: edsdoj.81f359711dbb4b4190faa0129dca17de
Database: Directory of Open Access Journals
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  Data: TYK2 kinase activity is required for functional type I interferon responses in vivo.
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  Data: <searchLink fieldCode="AR" term="%22Michaela+Prchal-Murphy%22">Michaela Prchal-Murphy</searchLink><br /><searchLink fieldCode="AR" term="%22Christian+Semper%22">Christian Semper</searchLink><br /><searchLink fieldCode="AR" term="%22Caroline+Lassnig%22">Caroline Lassnig</searchLink><br /><searchLink fieldCode="AR" term="%22Barbara+Wallner%22">Barbara Wallner</searchLink><br /><searchLink fieldCode="AR" term="%22Christian+Gausterer%22">Christian Gausterer</searchLink><br /><searchLink fieldCode="AR" term="%22Ingeborg+Teppner-Klymiuk%22">Ingeborg Teppner-Klymiuk</searchLink><br /><searchLink fieldCode="AR" term="%22Julianna+Kobolak%22">Julianna Kobolak</searchLink><br /><searchLink fieldCode="AR" term="%22Simone+Müller%22">Simone Müller</searchLink><br /><searchLink fieldCode="AR" term="%22Thomas+Kolbe%22">Thomas Kolbe</searchLink><br /><searchLink fieldCode="AR" term="%22Marina+Karaghiosoff%22">Marina Karaghiosoff</searchLink><br /><searchLink fieldCode="AR" term="%22Andras+Dinnyés%22">Andras Dinnyés</searchLink><br /><searchLink fieldCode="AR" term="%22Thomas+Rülicke%22">Thomas Rülicke</searchLink><br /><searchLink fieldCode="AR" term="%22Nicole+R+Leitner%22">Nicole R Leitner</searchLink><br /><searchLink fieldCode="AR" term="%22Birgit+Strobl%22">Birgit Strobl</searchLink><br /><searchLink fieldCode="AR" term="%22Mathias+Müller%22">Mathias Müller</searchLink>
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  Data: PLoS ONE, Vol 7, Iss 6, p e39141 (2012)
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  Data: Public Library of Science (PLoS), 2012.
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  Data: 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.
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  Data: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22723949/pdf/?tool=EBI; https://doaj.org/toc/1932-6203
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