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https://hdl.handle.net/2440/65922
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Type: | Journal article |
Title: | Cytoprotective roles of ERK and Akt in endoplasmic reticulum stress triggered by subtilase cytotoxin |
Author: | Tian, T. Zhao, Y. Nakajima, S. Huang, T. Yao, J. Paton, A. Paton, J. Kitamura, M. |
Citation: | Biochemical and Biophysical Research Communications, 2011; 410(4):852-858 |
Publisher: | Academic Press Inc |
Issue Date: | 2011 |
ISSN: | 0006-291X 1090-2104 |
Statement of Responsibility: | Tian Tian, Yang Zhao, Shotaro Nakajima, Tao Huang, Jian Yao, Adrienne W. Paton, James C. Paton, Masanori Kitamura |
Abstract: | Subtilase cytotoxin (SubAB) is the prototype of a distinct AB(5) toxin family produced by Shiga toxigenic Escherichia coli. Recent reports disclosed pro-apoptotic pathways triggered by SubAB, whereas its anti-apoptotic signals have not been elucidated. In the present study, we investigated pro-survival signaling elicited by SubAB, especially focusing on extracellular signal-regulated kinase (ERK) and Akt. We found that SubAB activated ERK and Akt, and inhibition of individual kinases enhanced SubAB-triggered apoptosis. SubAB induced endoplasmic reticulum (ER) stress, and other ER stress inducers mimicked the stimulatory effects of SubAB on ERK and Akt. Attenuation of ER stress reduced SubAB-induced phosphorylation of these kinases, suggesting involvement of the unfolded protein response (UPR). SubAB induced activation of protein kinase-like ER kinase (PERK) and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and phosphorylation of eIF2α by salubrinal caused activation of ERK and Akt, leading to cell survival. Dominant-negative inhibition of PERK enhanced SubAB-induced apoptosis and reduced phosphorylation of ERK and Akt. Furthermore, the anti-apoptotic effect of eIF2α was significantly reversed by inhibition of ERK and Akt. These results suggest cytoprotective roles of ERK and Akt in SubAB-triggered, ER stress-mediated apoptosis. |
Keywords: | Subtilase cytotoxin Apoptosis Extracellular signal-regulated kinase (ERK) Akt Endoplasmic reticulum stress Unfolded protein response (UPR) |
Rights: | © 2011 Elsevier Inc. All rights reserved. |
DOI: | 10.1016/j.bbrc.2011.06.078 |
Published version: | http://dx.doi.org/10.1016/j.bbrc.2011.06.078 |
Appears in Collections: | Aurora harvest Microbiology and Immunology publications |
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