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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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
Volume284
Issue number48
DOIs
Publication statusPublished - 2009 Nov 27

Fingerprint

Caspase 8
Small Interfering RNA
Phosphorylation
Apoptosis
Tyrosine
Anti-Idiotypic Antibodies
RNA Interference
Serine
Antibodies
CD95 Antigens
Integrins
Up-Regulation
erythrogenic toxin
SB 203580
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{8ea9cdad1ca542b1bdab7513605e1aa0,
title = "Procaspase 8 and bax are up-regulated by distinct pathways in streptococcal pyrogenic exotoxin B-induced apoptosis",
abstract = "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.",
author = "Chang, {Chia Wen} and Tsai, {Wan Hua} and Chuang, {Woei Jer} and Lin, {Yee Shin} and Wu, {Jiunn Jong} and Liu, {Ching Chuan} and Tsai, {Pei Jane} and Lin, {Ming T.}",
year = "2009",
month = "11",
day = "27",
doi = "10.1074/jbc.M109.020586",
language = "English",
volume = "284",
pages = "33195--33205",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "48",

}

Procaspase 8 and bax are up-regulated by distinct pathways in streptococcal pyrogenic exotoxin B-induced apoptosis. / Chang, Chia Wen; Tsai, Wan Hua; Chuang, Woei Jer; Lin, Yee Shin; Wu, Jiunn Jong; Liu, Ching Chuan; Tsai, Pei Jane; Lin, Ming T.

In: Journal of Biological Chemistry, Vol. 284, No. 48, 27.11.2009, p. 33195-33205.

Research output: Contribution to journalArticle

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

UR - http://www.scopus.com/inward/citedby.url?scp=70450252001&partnerID=8YFLogxK

U2 - 10.1074/jbc.M109.020586

DO - 10.1074/jbc.M109.020586

M3 - Article

C2 - 19801665

AN - SCOPUS:70450252001

VL - 284

SP - 33195

EP - 33205

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 48

ER -