EGF receptor clustering is induced by a 0.4 mT power frequency magnetic field and blocked by the EGF receptor tyrosine kinase inhibitor PD153035

EGF receptor clustering is induced by a 0.4 mT power frequency magnetic field and blocked by the EGF receptor tyrosine kinase inhibitor PD153035
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DOI:
10.1002/bem.20293
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发表时间:
2007-04-01
影响因子:
1.9
通讯作者:
Xia, Ruohong
Xia, Ruohong
中科院分区:
生物学4区
文献类型:
--
作者:
Jia, Caili;Zhou, Zhenjie;Xia, Ruohong

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采用原子力显微镜(AFM)、透射电子显微镜(TEM)和共焦激光扫描显微镜研究50 Hz 0.4 mT磁场(MF)对纯化的表皮生长因子受体(EGFR)和中国仓鼠肺(CHL)细胞膜中EGFR聚集的影响。结果表明,将纯化的 EGFR 暴露于 MF 30 分钟会诱导受体聚集。表观簇的峰高从 1.42 +/- 0.18(假暴露)增加到 3.08 +/- 0.38 nm(暴露),而平均半宽度从 21.7 +/- 2.2 增加到 33.0 +/- 4.0 nm。通过 TEM 也观察到类似的效果。用 EGFR 特异性酪氨酸激酶 (TK) 抑制剂 PD153035 (PD) 处理纯化的 EGFR,抑制了 MF 诱导的纯化蛋白的 EGFR 聚集,在不存在 EGF 的情况下,细胞膜中的受体也观察到了这种效应。这些结果强烈表明 50 Hz 0.4 mT MF 干扰 EGFR 信号传导通路,最有可能是通过与细胞质 TK 结构域相互作用。
Atomic force microscopy (AFM), transmission electron microscopy (TEM), and confocal laser scanning microscopy were used to investigate the effects of a 50 Hz 0.4 mT magnetic field (MF) on the clustering of purified epidermal growth factor receptors (EGFRs) and EGFRs in Chinese hamster lung (CHL) cell membrane. The results demonstrate that exposing purified EGFRs to the MF for 30 min induces receptor clustering. The peak height of apparent clusters increased from 1.42 +/- 0.18 (sham-exposed) to 3.08 +/- 0.38 nm (exposed) while the mean half-width increased from 21.7 +/- 2.2 to 33.0 +/- 4.0 nm. A similar effect was also observed by TEM. Treatment of purified EGFR with PD153035 (PD), an EGFR-specific tyrosine kinase (TK) inhibitor, inhibited the MF-induced EGFR clustering of the purified proteins, an effect also observed for the receptors in cell membrane in the absence of EGF. These results strongly suggest that the 50 Hz 0.4 mT MF interferes with the EGFR signaling pathway, most likely by interacting with the cytoplasmic TK domain.