Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function
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Andreas Wohlmann
Abstract
Thymic stromal lymphopoietin (TSLP) is an interleukin-(IL)-7-like cytokine with emerging pathological importance for the development of atopic diseases such as allergic asthma bronchiale. The TSLP receptor (TSLPR), a heterodimeric type I cytokine receptor, shares the IL-7R α-subunit with the IL-7 receptor system. The specific TSLPR α-chain shows similarities with the γc receptor chain, but has some unusual features within the receptor family in both its ligand-binding and cytoplasmic domain. The murine TSLPR signals via the signal transducers and activators of transcription STAT5 and STAT3, but is unique among cytokine receptors in that it activates STATs without the involvement of Janus (JAK) tyrosine kinases, but instead utilizes the Src type kinase Tec. Here, we show by Western blotting and reporter gene experiments in combination with the application of a specific JAK inhibitor that the human TSLP receptor, in contrast, requires the function of JAK1 and JAK2 for STAT activation. Moreover, we demonstrate that the human TSLPR mediates gene regulation not only through STAT5 and STAT3 but has also the potential to mediate transcription via STAT1. Our work should help to understand more thoroughly how TSLP triggers inflammatory responses in the course of atopic diseases.
©2010 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- EDITORIAL
- Highlight: Signal Transduction and Disease
- HIGHLIGHT: SIGNAL TRANSDUCTION AND DISEASE
- Phosphorylase and the origin of reversible protein phosphorylation
- β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver
- Glycome profiling using modern glycomics technology: technical aspects and applications
- Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity
- MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
- Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function
- GENES AND NUCLEIC ACIDS
- 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products
- PROTEIN STRUCTURE AND FUNCTION
- Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
- Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates
- The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers
- Antibacterial activity of radical scavengers against class Ib ribonucleotide reductase from Bacillus anthracis
- CELL BIOLOGY AND SIGNALING
- Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE
- The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells
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- An examination of the proteolytic activity for bovine pregnancy-associated glycoproteins 2 and 12
- Analysis of an autoproteolytic activity of rice yellow mottle virus silencing suppressor P1
- Identification of novel peptide inhibitors for human trypsins