Back to Search
Start Over
TYK2 kinase activity is required for functional type I interferon responses in vivo
- Source :
- PLoS ONE, PLoS ONE, Vol 7, Iss 6, p e39141 (2012)
- Publication Year :
- 2012
-
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 (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.
- Subjects :
- Mouse
Adaptive Immunity
Mice
Gene Order
Molecular Cell Biology
Mice, Knockout
Multidisciplinary
Janus kinase 2
biology
Janus kinase 1
Protein Stability
Animal Models
Innate Immunity
Cell biology
STAT Transcription Factors
Tyrosine kinase 2
Organ Specificity
Virus Diseases
Gene Targeting
Interferon Type I
Medicine
Signal Transduction
Research Article
Transcriptional Activation
Science
Immunology
Model Organisms
TYK2 Kinase
Genetics
Animals
Genetic Predisposition to Disease
Amino Acid Sequence
Biology
Janus Kinases
Base Sequence
Cyclin-dependent kinase 4
Immunity
Immune Defense
Interferon-beta
Protein kinase R
Molecular biology
Immunity, Innate
Enzyme Activation
Mutation
biology.protein
Cyclin-dependent kinase 9
Gene Function
Janus kinase
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....b6f82b0a92a959cb263f0158ceff3df0