The human epidermal growth factor receptor (EGFR/ERBB1) is a receptor tyrosine kinase (RTK) that forms activated oligomers in response to ligand. Much evidence indicates that EGFR/ERBB1 also forms oligomers in the absence of ligand, but the structure and physiological role of these ligand-independent oligomers remain unclear. To examine these features, we use fluorescence microscopy to measure the oligomer stability and FRET efficiency for homo- and hetero-oligomers of fluorescent protein-labeled forms of EGFR and its paralog, human epidermal growth factor receptor 2 (HER2/ERBB2) in vesicles derived from mammalian cell membranes. We observe that both receptors form ligand-independent oligomers at physiological plasma membrane concentrations. Mutations introduced in the kinase region at the active state asymmetric kinase dimer interface do not affect the stability of ligand-independent EGFR oligomers. These results indicate that ligand-independent EGFR oligomers form using interactions that are distinct from the EGFR active state.

中文翻译：

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EGFR 形成与活性状态不同的不依赖配体的寡聚体。

人表皮生长因子受体 (EGFR/ERBB1) 是一种受体酪氨酸激酶 (RTK)，可响应配体形成激活的寡聚体。许多证据表明，EGFR/ERBB1 在没有配体的情况下也能形成寡聚物，但这些不依赖配体的寡聚物的结构和生理作用仍不清楚。为了检查这些特征，我们使用荧光显微镜来测量荧光蛋白标记形式的 EGFR 及其旁系同源物、人表皮生长因子受体 2 (HER2/ERBB2) 的同源和异源寡聚体的寡聚体稳定性和 FRET 效率。来自哺乳动物细胞膜。我们观察到这两种受体在生理质膜浓度下形成不依赖配体的寡聚体。在活性状态不对称激酶二聚体界面的激酶区域中引入的突变不会影响不依赖配体的 EGFR 寡聚体的稳定性。这些结果表明不依赖配体的 EGFR 寡聚体使用不同于 EGFR 活性状态的相互作用形成。