Subtilase Cytotoxin Activates MAP Kinases through PERK and IRE1 Branches of the Unfolded Protein Response | Zendy

Yang Zhao | Zendy; Tian Tian | Zendy; Tao Huang | Zendy; Shotaro Nakajima | Zendy; Yukinori Saito | Zendy; Shuhei Takahashi | Zendy; Jian Yao | Zendy; Adrienne W. Paton | Zendy; James C. Paton | Zendy; Masanori Kitamura | Zendy

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Subtilase Cytotoxin Activates MAP Kinases through PERK and IRE1 Branches of the Unfolded Protein Response

Author(s) -

Yang Zhao,

Tian Tian,

Tao Huang,

Shotaro Nakajima,

Yukinori Saito,

Shuhei Takahashi,

Jian Yao,

Adrienne W. Paton,

James C. Paton,

Masanori Kitamura

Publication year - 2010

Publication title -

toxicological sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.352

H-Index - 183

eISSN - 1096-6080

pISSN - 1096-0929

DOI - 10.1093/toxsci/kfq368

Subject(s) - ask1 , kinase , unfolded protein response , p38 mitogen activated protein kinases , map kinase kinase kinase , microbiology and biotechnology , map2k7 , mapk14 , mitogen activated protein kinase , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , c raf , endoplasmic reticulum , protein kinase r , cyclin dependent kinase 9 , protein kinase a , signal transduction , biology , activator (genetics) , biochemistry , receptor

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 NH(2)-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.

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