重新审视一场争议：EGF 对 EGFR 二聚体稳定性的影响。
Revisiting a controversy: The effect of EGF on EGFR dimer stability.
机构信息
Institute of NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America; Department of Materials Science and Engineering, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America.
Institute of NanoBioTechnology, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America; Program in Molecular Biophysics, Johns Hopkins University, 3400 Charles Street, Baltimore, MD 21218, United States of America.
出版信息
Biochim Biophys Acta Biomembr. 2020 Jan 1;1862(1):183015. doi: 10.1016/j.bbamem.2019.07.003. Epub 2019 Jul 8.
EGFR is a receptor tyrosine kinase that plays a critical role in cell proliferation, differentiation, survival and migration. Its activating ligand, EGF, has long been believed to stabilize the EGFR dimer. Two research studies aimed at quantitative measurements of EGFR dimerization, however, have led to contradicting conclusions and have questioned this view. Given the controversy, here we sought to measure the dimerization of EGFR in the absence and in the presence of saturating EGF concentrations, and to tease out the effect of ligand on dimer stability, using a FRET-based quantitative method. Our measurements show that the dissociation constant is decreased ~150 times due to ligand binding, indicative of significant dimer stabilization. In addition, our measurements demonstrate that EGF binding induces a conformational change in the EGFR dimer.
表皮生长因子受体（EGFR）是一种受体酪氨酸激酶，在细胞增殖、分化、存活和迁移中发挥着关键作用。其激活配体表皮生长因子（EGF）长期以来被认为能稳定 EGFR 二聚体。然而，两项旨在对 EGFR 二聚化进行定量测量的研究得出了相互矛盾的结论，并对这一观点提出了质疑。鉴于存在争议，我们在这里试图使用基于荧光共振能量转移（FRET）的定量方法，在不存在和存在饱和 EGF 浓度的情况下测量 EGFR 的二聚化，并梳理配体对二聚体稳定性的影响。我们的测量结果表明，由于配体结合，解离常数降低了约 150 倍，表明二聚体得到了显著稳定。此外，我们的测量结果表明，EGF 结合诱导 EGFR 二聚体发生构象变化。
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