Tags

Type your tag names separated by a space and hit enter

Phosphorylated PKR contributes the induction of GRP94 under ER stress.
Biochem Biophys Res Commun. 2007 Aug 31; 360(3):615-20.BB

Abstract

Phosphorylated double-stranded RNA-dependent protein kinase (PKR) is thought to play an important role during ER stress induced cell death, but its molecular mechanism of action has not yet been clarified completely. To resolve this issue, we employed a PKR inhibitor together with ER stress inducers (tunicamycin, thapsigargin, and 2-deoxyglucose) and found that this treatment applied to SK-N-SH and HepG2 cells suppressed the expressional induction of 94kDa glucose regulated protein (GRP94) but not GRP78 proteins at both protein and mRNA levels. Although GRP94 mRNA increased, no significant difference was observed in the mRNA level of spliced X box binding protein 1 (XBP1) and reporter gene assay using GRP78 and GRP94 promoter with an ER stress response element (ERSE) showed that PKR inhibitor did not affect their activity. These results suggest that a novel mechanism other than ERSE-dependent mRNA transcription is required for the induction of GRP94 and phosphorylation of PKR contributes to the induction of GRP94 under ER stress.

Authors+Show Affiliations

Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 13-0033, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17612505

Citation

Ito, Mototsugu, et al. "Phosphorylated PKR Contributes the Induction of GRP94 Under ER Stress." Biochemical and Biophysical Research Communications, vol. 360, no. 3, 2007, pp. 615-20.
Ito M, Onuki R, Bando Y, et al. Phosphorylated PKR contributes the induction of GRP94 under ER stress. Biochem Biophys Res Commun. 2007;360(3):615-20.
Ito, M., Onuki, R., Bando, Y., Tohyama, M., & Sugiyama, Y. (2007). Phosphorylated PKR contributes the induction of GRP94 under ER stress. Biochemical and Biophysical Research Communications, 360(3), 615-20.
Ito M, et al. Phosphorylated PKR Contributes the Induction of GRP94 Under ER Stress. Biochem Biophys Res Commun. 2007 Aug 31;360(3):615-20. PubMed PMID: 17612505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphorylated PKR contributes the induction of GRP94 under ER stress. AU - Ito,Mototsugu, AU - Onuki,Reiko, AU - Bando,Yoshio, AU - Tohyama,Masaya, AU - Sugiyama,Yuichi, Y1 - 2007/06/26/ PY - 2007/06/15/received PY - 2007/06/16/accepted PY - 2007/7/7/pubmed PY - 2007/9/26/medline PY - 2007/7/7/entrez SP - 615 EP - 20 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 360 IS - 3 N2 - Phosphorylated double-stranded RNA-dependent protein kinase (PKR) is thought to play an important role during ER stress induced cell death, but its molecular mechanism of action has not yet been clarified completely. To resolve this issue, we employed a PKR inhibitor together with ER stress inducers (tunicamycin, thapsigargin, and 2-deoxyglucose) and found that this treatment applied to SK-N-SH and HepG2 cells suppressed the expressional induction of 94kDa glucose regulated protein (GRP94) but not GRP78 proteins at both protein and mRNA levels. Although GRP94 mRNA increased, no significant difference was observed in the mRNA level of spliced X box binding protein 1 (XBP1) and reporter gene assay using GRP78 and GRP94 promoter with an ER stress response element (ERSE) showed that PKR inhibitor did not affect their activity. These results suggest that a novel mechanism other than ERSE-dependent mRNA transcription is required for the induction of GRP94 and phosphorylation of PKR contributes to the induction of GRP94 under ER stress. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/17612505/Phosphorylated_PKR_contributes_the_induction_of_GRP94_under_ER_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(07)01339-3 DB - PRIME DP - Unbound Medicine ER -