Low electric fields induce ligand-independent activation of EGF receptor and ERK via electrochemical elevation of H+ and ROS concentrations

Tami Wolf-Goldberg, Alexander Barbul, Nadav Ben-Dov, Rafi Korenstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Physiological electric fields are involved in many biological processes and known to elicit their effects during long exposures ranging from a few hours to days. Following exposure to electric fields of physiological amplitude, epidermal growth factor receptor (EGFR) was demonstrated to be redistributed and upregulated with further intracellular signaling such as the MAPK signaling cascade. In our study we demonstrated EGFR activation and signaling induced by short train of pulsed low electric field (LEF) (10. V/cm, pulse-width 180. μs, 500. Hz, 2. min) in serum-free medium, following 24-hour starvation, and in the absence of exogenous EGF ligand, suggesting a ligand-independent pathway for EGFR activation. This ligandless activation was further confirmed by using neutralizing antibodies (LA1) that block the EGFR ligand-binding site. EGFR activation was found to be EGFR kinase dependent, yet with no dimerization following exposure to LEF. ERK activation was found to be mainly a result of EGFR downstream signaling though it partially occurred via EGFR-independent way. We demonstrate that reactive oxygen species and especially decrease in pH generated during exposure to LEF are involved in EGFR ligandless activation. We propose a possible mechanism for the LEF-induced EGFR ligand-independent activation and show activation of other receptor tyrosine kinases following exposure to LEF.

Original languageEnglish
Pages (from-to)1396-1408
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • EGFR
  • ERK
  • Electric field
  • Electrochemical product
  • PH
  • ROS

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