Abstract:
:Subtilase cytotoxin (SubAB), which is produced by certain strains of Shiga-toxigenic Escherichia coli (STEC), causes the 78-kDa glucose-regulated protein (GRP78/BiP) cleavage, followed by induction of endoplasmic reticulum (ER) stress, leading to caspase-dependent apoptosis via mitochondrial membrane damage by Bax/Bak activation. The purpose of the present study was to identify SubAB receptors responsible for HeLa cell death. Four proteins, NG2, α2β1 integrin (ITG), L1 cell adhesion molecule (L1CAM), and hepatocyte growth factor receptor (Met), were identified to be SubAB-binding proteins by immunoprecipitation and purification, followed by liquid chromatography-tandem mass spectrometry analysis. SubAB-induced Bax conformational change, Bax/Bak complex formation, caspase activation, and cell death were decreased in β1 ITG, NG2, and L1CAM small interfering RNA-transfected cells, but unexpectedly, BiP cleavage was still observed. Pretreatment of cells with a function-blocking β1 ITG antibody (monoclonal antibody [MAb] P5D2) enhanced SubAB-induced caspase activation; MAb P5D2 alone had no effect on caspase activation. Furthermore, we found that SubAB induced focal adhesion kinase fragmentation, which was mediated by a proteasome-dependent pathway, and caspase activation was suppressed in the presence of proteasome inhibitor. Thus, β1 ITG serves as a SubAB-binding protein and may interact with SubAB-signaling pathways, leading to cell death. Our results raise the possibility that although BiP cleavage is necessary for SubAB-induced apoptotic cell death, signaling pathways associated with functional SubAB receptors may be required for activation of SubAB-dependent apoptotic pathways.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Yahiro K,Satoh M,Morinaga N,Tsutsuki H,Ogura K,Nagasawa S,Nomura F,Moss J,Noda Mdoi
10.1128/IAI.01020-10subject
Has Abstractpub_date
2011-02-01 00:00:00pages
617-27issue
2eissn
0019-9567issn
1098-5522pii
IAI.01020-10journal_volume
79pub_type
杂志文章abstract::Borrelia burgdorferi, a tick-borne bacterial pathogen, causes a disseminated infection involving multiple organs known as Lyme disease. Surface proteins can directly participate in microbial virulence by facilitating pathogen dissemination via interaction with host factors. We show here that a fraction of the B. burgd...
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pub_type: 杂志文章
doi:10.1128/IAI.56.5.1096-1100.1988
更新日期:1988-05-01 00:00:00
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pub_type: 杂志文章
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.3.1.141-148.1971
更新日期:1971-01-01 00:00:00
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journal_title:Infection and immunity
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更新日期:1979-09-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.64.7.2716-2723.1996
更新日期:1996-07-01 00:00:00
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更新日期:1977-12-01 00:00:00
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更新日期:1972-03-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1989-09-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-11-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.38.1.316-324.1982
更新日期:1982-10-01 00:00:00
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更新日期:2003-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-03-01 00:00:00
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更新日期:2004-04-01 00:00:00
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journal_title:Infection and immunity
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doi:10.1128/IAI.57.3.805-809.1989
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journal_title:Infection and immunity
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更新日期:1999-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1998-08-01 00:00:00
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journal_title:Infection and immunity
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更新日期:2000-12-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:1990-12-01 00:00:00
abstract::Enterotoxigenic Escherichia coli (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed to be a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes ...
journal_title:Infection and immunity
pub_type: 杂志文章
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更新日期:2020-10-19 00:00:00
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journal_title:Infection and immunity
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更新日期:1991-10-01 00:00:00