TY - JOUR
T1 - Procaspase 8 and bax are up-regulated by distinct pathways in streptococcal pyrogenic exotoxin B-induced apoptosis
AU - Chang, Chia Wen
AU - Tsai, Wan Hua
AU - Chuang, Woei Jer
AU - Lin, Yee Shin
AU - Wu, Jiunn Jong
AU - Liu, Ching Chuan
AU - Tsai, Pei Jane
AU - Lin, Ming T.
PY - 2009/11/27
Y1 - 2009/11/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70450252001&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.020586
DO - 10.1074/jbc.M109.020586
M3 - Article
C2 - 19801665
AN - SCOPUS:70450252001
SN - 0021-9258
VL - 284
SP - 33195
EP - 33205
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 48
ER -