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Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1.

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.

Pubmed ID: 10650002


  • Urano F
  • Wang X
  • Bertolotti A
  • Zhang Y
  • Chung P
  • Harding HP
  • Ron D


Science (New York, N.Y.)

Publication Data

January 28, 2000

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK47119
  • Agency: NIEHS NIH HHS, Id: ES08681

Mesh Terms

  • 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