[Dependence of EGF receptor and STAT factor activation on redox of A431 cells].
Reactive oxygen species (ROS) were established to play an important role in cellular signaling as second messengers by integrating different pathways. Recently, we showed that EGF initiated a rapid tyrosine phosphorylation of both EGF-receptor and STAT factors with simultaneous increase in the intracellular ROS level. Now, we have investigated the effect of intracellular red-ox state on EGF- and H2O2-induced activation of EGF receptor, STAT1 and STAT3. We demonstrated that the pretreatment of A431 cells with antioxidant N-acetyl-L-cysteine (NAC) partly reduced the level of EGF-induced phosphorylation of proteins under investigation. Besides, H2O2-induced activation of EGF receptor, and STAT factors was fully prevented by NAC pretreatment. The inhibition of ROS generation by DPI declined EGF-dependent activation of EGF receptor and STAT factors to basal level. Our results demonstrate the essential role of cellular red-ox status in the modulation of EGF-mediated activation of receptor and STAT factors. We have postulated that EGF-induced ROS generation is a very important initial event promoting physiological activation of EGF receptor and subsequent STAT factor activation.
Gonchar
I V
IV
Institute of Cytology, RAS, St. Petersburg.
Burova
E B
EB
Dorosh
V N
VN
Gamaleĭ
I A
IA
Nikol'skiĭ
N N
NN
D000111:Acetylcysteine; D000975:Antioxidants; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D009861:Onium Compounds / Q000494:pharmacology; D010084:Oxidation-Reduction; D010766:Phosphorylation; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*
D000975:Antioxidants; D004268:DNA-Binding Proteins; D009861:Onium Compounds; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D004815:Epidermal Growth Factor; C007517:diphenyleneiodonium; D006861:Hydrogen Peroxide; D066246:ErbB Receptors; D000111:Acetylcysteine