EGFR forms ligand-independent oligomers that are distinct from the active state
EGFR forms ligand-independent oligomers that are distinct from the active state
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DOI：
10.1074/jbc.ra120.012852
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发表时间：
2020-09-18
影响因子：
4.8
通讯作者：
Leahy, Daniel J.
中科院分区：
文献类型：
--
作者：
Byrne, Patrick O.;Hristova, Kalina;Leahy, Daniel J.
人表皮生长因子受体(EGFR/ErbB1)是一种受体酪氨酸激酶(RTK)，能在配体的作用下形成活化的寡聚体。许多证据表明，在缺乏配体的情况下，EGFR/ErbB1也会形成寡聚体，但这些不依赖配体的寡聚体的结构和生理作用尚不清楚。为了检验这些特征，我们使用荧光显微镜来测量来自哺乳动物细胞膜的囊泡中荧光蛋白标记形式的EGFR及其类似物人表皮生长因子受体2(HER2/ERBB2)的同种和异种寡聚体的稳定性和FRET效率。我们观察到，在生理质膜浓度下，这两种受体形成不依赖配体的寡聚体。在激活状态的不对称激酶二聚体界面的激活区引入的突变不会影响非配体依赖的EGFR寡聚体的稳定性。这些结果表明，非配体依赖的EGFR寡聚体形成的相互作用不同于EGFR的活性状态。
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.