Predominance of activated EGFR higher-order oligomers on the cell surface
Predominance of activated EGFR higher-order oligomers on the cell surface
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DOI：
10.1080/08977190802442187
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发表时间：
2008-01-01
期刊：
影响因子：
1.8
通讯作者：
Burgess, Antony W.
中科院分区：
文献类型：
--
作者：
Clayton, Andrew H. A.;Orchard, Suzanne G.;Burgess, Antony W.
表皮生长因子受体（EGFR）激酶通常被认为是通过配体诱导的二聚化或预形成的二聚体内配体诱导的构象变化激活的。我们报道了在完整细胞表面配体诱导的更高阶EGFR寡聚化和EGFR磷酸化之间的关系。我们结合了寿命检测的福斯特共振能量转移，作为受体磷酸化状态和图像相关光谱的探针，提取活化与未活化的EGFR的相对缔合状态，以确定活性（磷酸化）和非活性簇的受体平均数的比率。配体诱导的活性簇中的受体至少是非活性簇的四倍。与EGFR二聚体是主要的活性形式的流行观点相反，我们的数据确定高阶EGFR寡聚体是与配体活化的EGFR酪氨酸激酶相关的主要物质。
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.