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- Title
Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1.
- Authors
Urano, F; Wang, X; Bertolotti, A; Zhang, Y; Chung, P; Harding, H P; Ron, D
- Abstract
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.
- Publication
Science (New York, N.Y.), 2000, Vol 287, Issue 5453, p664
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.287.5453.664