[Metalloprotease-mediated HB-EGF release regulates EGF receptor transactivation in A431 cells under oxidative stress].
We have shown earlier that H2O2 induces EGF receptor transactivation in different cells overexpressing EGF receptor. Mechanism of H2O2-induced EGF receptor transactivation in A431 human epidermoid carcinoma cells was examined in this work. We have demonstrated autophosphorylation of Tyr1045, 1068, 1148, 1173 as well as phosphorylation of Tyr845 of EGF receptor in response to H2O2, as assessed by autophosphorylation specific antibody. Tyrosine phosphorylation of EGF receptor by H2O2 did not involve receptor autophosphorylation at Tyr992. Blocking functions of metalloproteases by broad-spectrum inhibitor GM6001 suppressed H2O2-induced phosphorylation of EGF receptor, suggesting dependence of the transactivation on metalloproteases activity. To elucidate the possible role of EGF receptor agonists in its activation we used HB-EGF and TGF-alpha neutralizing antibody. H2O2-induced EGF receptor phosphorylation was inhibited by HB-EGF, but not TGF-alpha, neutralizing antibody. Taken together, our data suggest that, in human epidermoid carcinoma A431 cells, H2O2 stimulates EGF receptor transactivation via metalloprotease-dependent HB-EGF release and autophosphorylation.
Smirnova
I S
IS
Gonchar
I V
IV
Shatrova
A N
AN
Nikol'skiĭ
N N
NN
Burova
E B
EB
D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D045726:Metalloproteases / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction; D015533:Transcriptional Activation
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D006861:Hydrogen Peroxide; D066246:ErbB Receptors; D045726:Metalloproteases