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Science 287 (5453): 664-666

Copyright © 2000 by the American Association for the Advancement of Science

Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1

Fumihiko Urano, XiaoZhong Wang, Anne Bertolotti, Yuhong Zhang, Peter Chung, Heather P. Harding, David Ron *

Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha -/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals.

Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA.
*   To whom correspondence should be addressed: E-mail: ron{at}saturn.med.nyu.edu


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Late Activation of Stress-activated Protein Kinases/c-Jun N-terminal Kinases Triggered by Cisplatin-induced DNA Damage in Repair-defective Cells.
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J. Biol. Chem. 286, 12991-13001
   Abstract »    Full Text »    PDF »
Potent and Selective Inhibitors of the Inositol-requiring Enzyme 1 Endoribonuclease.
K. Volkmann, J. L. Lucas, D. Vuga, X. Wang, D. Brumm, C. Stiles, D. Kriebel, A. Der-Sarkissian, K. Krishnan, C. Schweitzer, et al. (2011)
J. Biol. Chem. 286, 12743-12755
   Abstract »    Full Text »    PDF »
The unfolded protein response transducer IRE1{alpha} prevents ER stress-induced hepatic steatosis.
K. Zhang, S. Wang, J. Malhotra, J. R. Hassler, S. H. Back, G. Wang, L. Chang, W. Xu, H. Miao, R. Leonardi, et al. (2011)
EMBO J. 30, 1357-1375
   Abstract »    Full Text »    PDF »
Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic {beta}-cells by stearoyl-CoA desaturase and Elovl6.
C. D. Green and L. K. Olson (2011)
Am J Physiol Endocrinol Metab 300, E640-E649
   Abstract »    Full Text »    PDF »
Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells.
E. Matsushita, N. Asai, A. Enomoto, Y. Kawamoto, T. Kato, S. Mii, K. Maeda, R. Shibata, S. Hattori, M. Hagikura, et al. (2011)
Mol. Biol. Cell 22, 736-747
   Abstract »    Full Text »    PDF »
Subtilase Cytotoxin Activates MAP Kinases through PERK and IRE1 Branches of the Unfolded Protein Response.
Y. Zhao, T. Tian, T. Huang, S. Nakajima, Y. Saito, S. Takahashi, J. Yao, A. W. Paton, J. C. Paton, and M. Kitamura (2011)
Toxicol. Sci. 120, 79-86
   Abstract »    Full Text »    PDF »
Deletion of Nck1 attenuates hepatic ER stress signaling and improves glucose tolerance and insulin signaling in liver of obese mice.
M. Latreille, M.-K. Laberge, G. Bourret, L. Yamani, and L. Larose (2011)
Am J Physiol Endocrinol Metab 300, E423-E434
   Abstract »    Full Text »    PDF »
Bifunctional Apoptosis Regulator (BAR), an Endoplasmic Reticulum (ER)-associated E3 Ubiquitin Ligase, Modulates BI-1 Protein Stability and Function in ER Stress.
J. Rong, L. Chen, J. I. Toth, M. Tcherpakov, M. D. Petroski, and J. C. Reed (2011)
J. Biol. Chem. 286, 1453-1463
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Neuronal Apoptosis Induced by Endoplasmic Reticulum Stress Is Regulated by ATF4-CHOP-Mediated Induction of the Bcl-2 Homology 3-Only Member PUMA.
Z. Galehdar, P. Swan, B. Fuerth, S. M. Callaghan, D. S. Park, and S. P. Cregan (2010)
J. Neurosci. 30, 16938-16948
   Abstract »    Full Text »    PDF »
Biology of Endoplasmic Reticulum Stress in the Heart.
J. Groenendyk, P. K. Sreenivasaiah, D. H. Kim, L. B. Agellon, and M. Michalak (2010)
Circ. Res. 107, 1185-1197
   Abstract »    Full Text »    PDF »

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