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SHR Neuro Krebs Kardio Lipid

Grunert, T; Leitner, NR; Marchetti-Deschmann, M; Miller, I; Wallner, B; Radwan, M; Vogl, C; Kolbe, T; Kratky, D; Gemeiner, M; Allmaier, G; Müller, M; Strobl, B.
A comparative proteome analysis links tyrosine kinase 2 (Tyk2) to the regulation of cellular glucose and lipid metabolism in response to poly(I:C).
J Proteomics. 2011; 74(12): 2866-2880. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Kratky Dagmar

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Number of Figures: 7
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Tyrosine kinase 2 (Tyk2) is an integral part of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway which relays intracellular signals of various cytokines. Tyk2 crucially contributes to host defense mechanisms against microbial pathogens and to tumor surveillance but also facilitates immune pathologies. Here we investigated the impact of Tyk2 on the macrophage proteome using the synthetic double-stranded RNA analog polyinosinic acid-polycytidylic acid (poly(I:C)) as a mimicry of viral infections. By means of 2D-DIGE in connection with PMF obtained by MALDI-MS and sequence tag determination by MS/MS we unambiguously identified eighteen protein spots corresponding to sixteen distinct proteins that are regulated by poly(I:C) and differentially expressed between wildtype (WT) and Tyk2-deficient macrophages. The majority of these proteins are functionally assigned to cellular immune responses and to metabolism. We show for selected metabolic enzymes, i.e. triosephosphate isomerase (TIM), ATP-citrate synthase (ACLY) and long-chain-fatty-acid-CoA ligase 4 (ACSL4), that Tyk2 affects protein expression transcriptionally and post-transcriptionally. We furthermore confirm the involvement of Tyk2 in the regulation of lipid and carbohydrate metabolism at the level of metabolites. Taken together, our results provide new evidence for important functions of Tyk2 at the molecular interface between innate immunity and cellular metabolism. Copyright © 2011 Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Carbohydrate Metabolism - drug effects
Gene Expression Regulation - drug effects
Glucose - genetics
Immunity, Innate - drug effects
Interferon Inducers - pharmacology
Lipid Metabolism - drug effects
Macrophages - cytology
Mice -
Mice, Knockout -
Poly I-C - pharmacology
Proteome - biosynthesis
TYK2 Kinase - genetics

Find related publications in this database (Keywords)
Mass spectrometry
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