Procaspase 8 and bax are up-regulated by distinct pathways in streptococcal pyrogenic exotoxin B-induced apoptosis

Chia Wen Chang, Wan Hua Tsai, Woei Jer Chuang, Yee Shin Lin, Jiunn Jong Wu, Ching Chuan Liu, Pei Jane Tsai, Ming T. Lin

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17 Citations (Scopus)


We have previously identified integrin αvβ 3 and Fas as receptors for the streptococcal pyrogenic exotoxin B (S PE B), and G308S, a mutant of SPE B that binds to Fas only. In the current study we found that after binding to α vβ3, 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-αVβ3 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.

Original languageEnglish
Pages (from-to)33195-33205
Number of pages11
JournalJournal of Biological Chemistry
Issue number48
Publication statusPublished - 2009 Nov 27

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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