[HTML][HTML] TYK2 Kinase Activity Is Required for Functional Type I Interferon Responses In Vivo
M Prchal-Murphy, C Semper, C Lassnig, B Wallner… - PloS one, 2012 - journals.plos.org
M Prchal-Murphy, C Semper, C Lassnig, B Wallner, C Gausterer, I Teppner-Klymiuk…
PloS one, 2012•journals.plos.orgTyrosine 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, ie,
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 …
cytokine signalling. In vitro analyses suggest that TYK2 also has kinase-independent, ie,
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 …
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.
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