Erk1Erk2
H2O2-Induced Transactivation of EGF Receptor Requires Src and Mediates
ERK1/2, but not Akt, Activation in Renal Cells.
Zhuang S, Schnellmann RG.
Department of Pharmaceutical Sciences, Medical University of South Carolina,
Charleston, SC, USA.
Although oxidative stress activates epidermal growth factor receptor (EGFR),
ERK1/2 and Akt in a number of cell types, the mechanisms by which oxidative
stress activates these kinases are not well defined in renal epithelial cells.
Exposure of primary cultures of rabbit renal proximal tubular cells (RPTC) to
hydrogen peroxide (H2O2) stimulated Src, EGFR, ERK1/2, and Akt activation in a
time-dependent manner as determined by the phosphorylation of each protein. The
Src inhibitor PP1 completely blocked EGFR, ERK1/2 and Akt phosphorylation
following H2O2 exposure. In contrast, blockade of the EGFR by AG1478 inhibited
phosphorylation of ERK1/2, but not Src or Akt phosphorylation following H2O2
exposure. Exogenous EGF stimulated EGFR, ERK1/2 and Akt activation and the EGFR
inhibitor blocked phorphorylation of ERK1/2 and Akt. The presence of PP1, but
not AG1478, significantly accelerated H2O2-induced cell death. These results
suggest that Src mediates H2O2-induced EGFR transactivation. H2O2- and
EGF-induced ERK1/2 activation is mediated by EGFR, whereas Akt is activated by
Src independent of EGFR following H2O2 exposure. Src-mediated EGFR
transactivation contributes to a survival response following oxidative injury.
PMID: 14871881 [PubMed - as supplied by publisher]