Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1.
Journal:
Science 2000 JanAuthors:
Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, 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.
...[more] 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.[less]
Mesh Headings:
Animals, Cell Line, Cells, Cultured, Endoplasmic Reticulum, Endoribonucleases, Enzyme Activation, Gene Targeting, Humans, JNK Mitogen-Activated Protein Kinases, Membrane Proteins, Mitogen-Activated Protein Kinases, Multienzyme Complexes, Protein Kinases, Protein-Serine-Threonine Kinases, Proteins, Rats, Recombinant Fusion Proteins, TNF Receptor-Associated Factor 2, Thapsigargin, Two-Hybrid System Techniques, eIF-2 Kinase