UV activates growth factor receptors via reactive oxygen intermediates.

UV activates growth factor receptors via reactive oxygen intermediates.
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DOI:
10.1083/jcb.133.1.211
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发表时间:
1996-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Adamson ED
Adamson ED
中科院分区:
其他
文献类型:
--
作者:
Huang RP;Wu JX;Fan Y;Adamson ED

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哺乳动物细胞暴露于UV照射诱导早期生长反应-1基因(Egr-1)的快速和瞬时表达,该基因编码在细胞存活中起作用的转录因子。这些信号从照射的细胞表面可能涉及一个以上的途径,我们在这里表明,一个重要的途径涉及激活几个生长因子受体的活性氧中间体(ROI)。紫外线照射引起小鼠NIH 3 T3成纤维细胞和HC 11小鼠乳腺细胞表皮生长因子受体(EGFR)酪氨酸磷酸化。通过照射细胞的EGFR激活被苏拉明、抗氧化剂和显性负性EGFR的存在废除。UV诱导活化的EGFR与SOS、Grb 2、PLC γ和SHC之间的复合物的形成,所述复合物可以用EGFR的抗体沉淀。UV对EGFR的激活被H2 O2模拟,表明ROI可能在EGFR激活的上游起作用。我们的观察结果支持这一假设,即ROI和生长因子受体在导致Egr-1表达和活性增强的UV信号的早期步骤中起作用。
Exposure of mammalian cells to UV irradiation induces rapid and transient expression of early growth response-1 gene (Egr-1) encoding a transcription factor that plays a role in cell survival. These signals from the irradiated cell surface are likely to involve more than one pathway, and we show here that an essential pathway involves activation of several growth factor receptors by reactive oxygen intermediates (ROI). UVC irradiation causes the tyrosine phosphorylation of EGF receptor (EGFR) in mouse NIH 3T3 fibroblasts and HC11 mouse mammary cells. EGFR activation by irradiation of cells is abrogated by suramin, by antioxidants, and by the presence of a dominant negative EGFR. UV induces the formation of complexes between activated EGFR and SOS, Grb2, PLC gamma, and SHC that can be precipitated with antibodies to EGFR. The activation of EGFR by UV is mimicked by H2O2, suggesting that ROI may function upstream of EGFR activation. Our observations support the hypothesis that ROI and growth factor receptors operate in the early steps of the UV signal that lead to the enhanced expression and activity of Egr-1.