Procaspase 8 and Bax Are Up-regulated by Distinct Pathways in Streptococcal Pyrogenic Exotoxin B-induced Apoptosis
| Autor: | Ching Chuan Liu, Pei Jane Tsai, Wan Hua Tsai, Jiunn Jong Wu, Yee Shin Lin, Woei Jer Chuang, Ming T. Lin, Chia Wen Chang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Small interfering RNA
Pyridines Immunoblotting Exotoxins Apoptosis Caspase 8 Models Biological Biochemistry Antibodies chemistry.chemical_compound Bcl-2-associated X protein Bacterial Proteins Cell Line Tumor Humans Gene silencing fas Receptor Enzyme Inhibitors Phosphorylation Molecular Biology bcl-2-Associated X Protein biology Reverse Transcriptase Polymerase Chain Reaction Mechanisms of Signal Transduction Imidazoles Tyrosine phosphorylation Cell Biology Janus Kinase 2 Tyrphostins Integrin alphaVbeta3 Molecular biology Recombinant Proteins Up-Regulation STAT1 Transcription Factor chemistry biology.protein Mutant Proteins RNA Interference Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 284:33195-33205 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m109.020586 |
| Popis: | We have previously identified integrin alpha(v)beta(3) and Fas as receptors for the streptococcal pyrogenic exotoxin B (SPE B), and G308S, a mutant of SPE B that binds to Fas only. In the current study we found that after binding to alpha(v)beta(3), SPE B stimulated the tyrosine phosphorylation of JAK2 and STAT1. STAT1 tyrosine phosphorylation was inhibited by a JAK2 inhibitor, AG490, short interfering RNA (siRNA) silencing of JAK2, and anti-alpha(V)beta(3) antibody. AG490 also decreased the binding of tyrosine-phosphorylated STAT1 to the procaspase 8 promoter, decreasing procaspase 8 expression, suggesting that SPE B up-regulates procaspase 8 expression via the JAK2/STAT1 pathway. Alternatively, both SPE B and G308S increased STAT1 phosphorylation at serine 727, which was inhibited by anti-Fas antibody, a p38 inhibitor, SB203580, and siRNA silencing of p38. In addition, SPE B and G308S increased binding of serine-phosphorylated STAT1 to the Bax promoter and Bax expression, which was decreased by SB203580. SPE B and G308S-stimulated Bax expression was also inhibited by anti-Fas antibody. These findings suggest that Fas mediate SPE B-induced Bax expression through p38. Silencing of JAK2 or p38 by siRNA blocked procaspase 8 expression, whereas only p38 siRNA decreased Bax expression. Furthermore, JAK2 inhibition and p38 inhibition reduced SPE B-induced apoptosis, but only p38 inhibition blocked G308S-induced apoptosis. |
| Databáze: | OpenAIRE |
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