title: The impact of tyrosine kinase 2 (Tyk2) on the proteome of murine macrophages and their response to lipopolysaccharide (LPS).
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.
authors.affiliation: Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Marta
authors.initials: M
authors.lastname: Radwan
authors.forename: Ingrid
authors.initials: I
authors.lastname: Miller
authors.forename: Tom
authors.initials: T
authors.lastname: Grunert
authors.forename: Martina
authors.initials: M
authors.lastname: Marchetti-Deschmann
authors.forename: Claus
authors.initials: C
authors.lastname: Vogl
authors.forename: Niaobh
authors.initials: N
authors.lastname: O'Donoghue
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dunn
authors.forename: Thomas
authors.initials: T
authors.lastname: Kolbe
authors.forename: Günter
authors.initials: G
authors.lastname: Allmaier
authors.forename: Manfred
authors.initials: M
authors.lastname: Gemeiner
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.forename: Birgit
authors.initials: B
authors.lastname: Strobl
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D020652:Peptide Elongation Factor 2 / Q000096:biosynthesis; D054464:Peroxiredoxins / Q000096:biosynthesis; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis; D020543:Proteome / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053634:TYK2 Kinase / Q000172:deficiency / Q000502:physiology*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D020652:Peptide Elongation Factor 2; D054464:Peroxiredoxins; D017396:Plasminogen Activator Inhibitor 2; D020543:Proteome; D012333:RNA, Messenger; D053634:TYK2 Kinase; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C489899:Prdx1 protein, mouse; C499356:Tyk2 protein, mouse