The impact of tyrosine kinase 2 (Tyk2) on the proteome of murine macrophages and their response to lipopolysaccharide (LPS)

Radwan, Marta, Miller, Ingrid, Grunert, Tom, Marchetti-Deschmann, Martina, Vogl, Claus, O'Donoghue, Niaobh, Dunn, Michael J., Kolbe, Thomas, Allmaier, Günter, Gemeiner, Manfred, Müller, Mathias and Strobl, Birgit 2008. The impact of tyrosine kinase 2 (Tyk2) on the proteome of murine macrophages and their response to lipopolysaccharide (LPS). Proteomics 8 (17) , pp. 3469-3485. 10.1002/pmic.200800260

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Abstract

Tyrosine kinase 2 (Tyk2) belongs to the Janus kinase (Jak) family and is involved in signalling via a number of cytokines. Tyk2-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxin shock. Macrophages are key players in the pathogenesis of endotoxin shock and, accordingly, defects in the LPS responses of Tyk2−/− macrophages have been reported. In the present study, the molecular role of Tyk2 is investigated in more detail using a proteomics approach. 2-D DIGE was applied to compare protein patterns from wild-type and Tyk2−/− macrophages and revealed significant differences in protein expression patterns between the genotypes before and after LPS treatment. Twenty-one proteins deriving from 25 differentially expressed spots were identified by MALDI/ESI MS. Among them, we show for N-myc interactor that its mRNA transcription/stability is positively influenced by Tyk2. In contrast, LPS-induced expression of plasminogen activator 2 protein but not mRNA is strongly enhanced in the absence of Tyk2. Our data furthermore suggest an influence of Tyk2 on the subcellular distribution of elongation factor 2 and on LPS-mediated changes in the peroxiredoxin 1 spot pattern. Thus, our results imply regulatory roles of Tyk2 at multiple levels and establish novel connections between Tyk2 and several cellular proteins.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QR Microbiology
Uncontrolled Keywords:	2-D DIGE; Jaks; LPS; MS; Murine macrophages.
Publisher:	Wiley
ISSN:	1615-9853
Last Modified:	12 Oct 2016 03:19
URI:	https://orca.cardiff.ac.uk/id/eprint/67819

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