表皮生长因子受体（EGFR）是一种定位在质膜上的受体酪氨酸激酶，在配体的刺激下会发生同源或异源二聚化从而激活下游信号通路，在细胞生长、增殖和分化等正常生理过程中发挥重要作用；EGFR异常激活往往会导致上皮细胞肿瘤的发生。肺癌作为全球范围内危害最大的疾病之一，其发生与EGFR异常激活密切相关。毫无疑问，研究EGFR 的结构和激活机制具有重要的理论意义和现实意义。目前这方面的研究主要集中在EGFR本身，而往往忽略了细胞质膜在EGFR激活中的重要功能。因此，我们拟从EGFR 与质膜相互作用的角度出发，利用目前国际上最先进的超分辨显微镜成像技术-随机光学重建显微镜技术(STORM)，并结合核磁共振实验、生化分析、细胞功能实验以及临床样本研究，揭示EGFR在正常细胞和肿瘤细胞质膜中的动态定位，鉴定参与EGFR动态定位的蛋白结构域和特定细胞质膜成份，阐明EGFR通过质膜动态定位参与其活性调控的新机制。

Epidermal growth factor receptor (EGFR) is a type of receptor tyrosine kinase mainly localized on plasma membrane. Upon stimulation by its ligands, EGFR forms homodimer or heterodimer and activates downstream signaling and plays an important role in cell growth, proliferation and differentiation under physiological condition. Deregulated activation of EGFR and its downstream signaling contribute to epithelial tumor formation, e.g., lung cancer, as one of the most deadly diseases worldwide, has been proven to be strongly associated with EGFR oncogenic activation. Therefore, to study EGFR structure and activating mechanism is of great importance, not only from theoretical standpoint but also from therapeutic standpoint. However, most of current studies mainly focus on EGFR itself while neglecting the interaction of EGFR with plasma membrane. Here we propose to study EGFR strucutre and activating mechanism via the angle of the interaction of EGFR and membrane. We will take advantage of the super-resolution microscopy imaging system-stochastic optical reconstruction microscopy (STORM), with the combination of NMR, biochemical assay, functional study as well as clincal specimen analyses to uncover the dynamic distribution pattern of EGFR on plasma membrane of normal epithelial cell and lung tumor cell. Our study will hopefully uncover the novel mechanisms through identification of the exact EGFR protein domain and specific plasma membrane components involved in EGFR dynamic membrane distribution and EGFR activation.