The epidermal growth factor receptor (EGFR) kinase is generally considered to be activated by either ligand-induced dimerisation or a ligand-induced conformational change within pre-formed dimers. We report the relationship between ligand-induced higher-order EGFR oligomerization and EGFR phosphorylation on the surface of intact cells. We have combined lifetime-detected Forster resonance energy transfer, as a probe of the receptor phosphorylation state and image correlation spectroscopy, to extract the relative association state of activated versus unactivated EGFR, to determine the ratio of the average number of receptors for active (phosphorylated) and inactive clusters. There are at least four times as many receptors in the ligand-induced active clusters than inactive clusters. Contrary to the prevailing view that the EGFR dimer is the predominant, active form, our data determine that higher-order EGFR oligomers are the dominant species associated with the ligand activated EGFR tyrosine kinase.

中文翻译：

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活化的EGFR高阶低聚物在细胞表面上占主导地位。

通常认为，表皮生长因子受体（EGFR）激酶是通过预先形成的二聚体中的配体诱导的二聚作用或配体诱导的构象变化激活的。我们报告完整细胞表面上配体诱导的高阶EGFR寡聚和EGFR磷酸化之间的关系。我们结合了生命周期检测到的Forster共振能量转移，作为受体磷酸化状态和图像相关光谱的探针，以提取活化与未活化EGFR的相对缔合状态，以确定活性（磷酸化）受体的平均数之比）和不活动的集群。配体诱导的活性簇中的受体至少是非活性簇的四倍。