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https://hdl.handle.net/2440/66036
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Type: | Journal article |
Title: | Subtilase cytotoxin activates MAP kinases through PERK and IRE1 branches of the unfolded protein response |
Author: | Zhao, Y. Tian, T. Huang, T. Nakajima, S. Saito, Y. Takahashi, S. Yao, J. Paton, A. Paton, J. Kitamura, M. |
Citation: | Toxicological Sciences, 2011; 120(1):79-86 |
Publisher: | Oxford Univ Press |
Issue Date: | 2011 |
ISSN: | 1096-6080 1096-0929 |
Statement of Responsibility: | Yang Zhao, Tian Tian, Tao Huang, Shotaro Nakajima, Yukinori Saito, Shuhei Takahashi, Jian Yao, Adrienne W. Paton, James C. Paton, and Masanori Kitamura |
Abstract: | Recent reports suggested involvement of mitogen-activated protein (MAP) kinases in the pathogenesis of Shiga toxin–induced hemolytic uremic syndrome (HUS). In the present study, we investigated a role for subtilase cytotoxin (SubAB), a possible trigger for HUS, in the regulation of MAP kinases. Treatment of cells with SubAB caused phosphorylation of c-Jun NH2-terminal kinase, extracellular signal-regulated kinase (ERK), and p38 MAP kinase. It was associated with activation of activator protein 1 (AP-1) and induction of AP-1–dependent transcription. SubAB induced the unfolded protein response (UPR) and consequently caused MAP kinase activation. SubAB led to induction of three major branches of the UPR, and the protein kinase–like endoplasmic reticulum kinase and inositol-requiring ER-to-nucleus signal kinase 1 pathways were responsible for the activation of MAP kinases. These results elucidated the potential of SubAB to trigger MAP kinase pathways via the UPR, which may contribute to the pathogenesis of Shiga toxin–induced HUS. |
Keywords: | Cell Line Epithelial Cells Animals Rats Subtilisins eIF-2 Kinase Mitogen-Activated Protein Kinases Escherichia coli Proteins Membrane Proteins Transcription Factor AP-1 Blotting, Western Transfection Enzyme Activation Unfolded Protein Response Protein Serine-Threonine Kinases |
Rights: | © The Author 2010. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. |
DOI: | 10.1093/toxsci/kfq368 |
Published version: | http://dx.doi.org/10.1093/toxsci/kfq368 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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