Bibliographic Details
| 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 |
