Cell Signaling and Stress Responses

Cold Spring Harb Perspect Biol. 2016 Oct 3;8(10):a006072. doi: 10.1101/cshperspect.a006072.


Stress-signaling pathways are evolutionarily conserved and play an important role in the maintenance of homeostasis. These pathways are also critical for adaptation to new cellular environments. The endoplasmic reticulum (ER) unfolded protein response (UPR) is activated by biosynthetic stress and leads to a compensatory increase in ER function. The JNK and p38 MAPK signaling pathways control adaptive responses to intracellular and extracellular stresses, including environmental changes such as UV light, heat, and hyperosmotic conditions, and exposure to inflammatory cytokines. Metabolic stress caused by a high-fat diet represents an example of a stimulus that coordinately activates both the UPR and JNK/p38 signaling pathways. Chronic activation of these stress-response pathways ultimately causes metabolic changes associated with obesity and altered insulin sensitivity. Stress-signaling pathways, therefore, represent potential targets for therapeutic intervention in the metabolic stress response and other disease processes.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • MAP Kinase Signaling System
  • Oxidative Stress*
  • Signal Transduction*
  • Unfolded Protein Response
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • p38 Mitogen-Activated Protein Kinases