EGF Receptor Exposed to Oxidative Stress Acquires Abnormal Phosphorylation and Aberrant Activated Conformation That Impairs Canonical Dimerization
2011

How Oxidative Stress Affects EGFR Activation

publication Evidence: moderate

Author Information

Author(s): Simone Filosto, Elaine M. Khan, Majid Ravid, Tommer Goldkorn

Primary Institution: University of California School of Medicine, Davis, California, United States of America

Hypothesis

Oxidative stress activates EGFR in a ligand-independent manner that does not involve canonical dimerization.

Conclusion

Oxidative stress induces a novel active conformation of EGFR that is resistant to traditional inhibitors and does not require ligand binding for activation.

Supporting Evidence

  • Oxidative stress activates EGFR differently than its ligand, EGF.
  • EGFR activation under oxidative stress does not induce classical receptor dimerization.
  • EGFR exposed to oxidative stress remains active and is trafficked to a peri-nuclear region.

Takeaway

When cells are stressed by things like smoke or hydrogen peroxide, a protein called EGFR can get turned on without needing its usual helper, which can lead to problems in how the cell works.

Methodology

The study used A549 cells and NIH-3T3 cells to investigate the effects of oxidative stress on EGFR activation through various biochemical techniques.

Limitations

The study primarily focused on specific cell lines and may not fully represent all cellular contexts.

Digital Object Identifier (DOI)

10.1371/journal.pone.0023240

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