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