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Gewählte Publikation:

Radwan, M; Miller, I; Grunert, T; Marchetti-Deschmann, M; Vogl, C; O'Donoghue, N; Dunn, MJ; Kolbe, T; Allmaier, G; Gemeiner, M; Müller, M; Strobl, B.
(2008): The impact of tyrosine kinase 2 (Tyk2) on the proteome of murine macrophages and their response to lipopolysaccharide (LPS).
Proteomics. 2008; 8(17):3469-3485 FullText FullText_BOKU

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.
Autor*innen der BOKU Wien:
Kolbe Thomas
BOKU Gendermonitor:

Find related publications in this database (using NML MeSH Indexing)
Animals -
Cell Cycle Proteins - biosynthesis
Electrophoresis, Gel, Two-Dimensional -
Female -
Intracellular Signaling Peptides and Proteins -
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Male -
Mice -
Mice, Knockout -
Peptide Elongation Factor 2 - biosynthesis
Peroxiredoxins - biosynthesis
Plasminogen Activator Inhibitor 2 - biosynthesis
Proteome - drug effects
RNA, Messenger - metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization -
TYK2 Kinase - deficiency

Find related publications in this database (Keywords)
2-D DIGE
Jaks
LPS
MS
murine macrophages


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