Single-molecule imaging reveals the stoichiometry change of epidermal growth factor receptor during transactivation by β_2-adrenergic receptor  

作　　者：Mingliang Zhang Kangmin He Jimin Wu Nan Li Jinghe Yuan Wei Zhou Zi Ye Zijian Li Han Xiao Zhizhen Lv Youyi Zhang Xiaohong Fang 

机构地区：[1]Institute of Vascular Medicine of Third Hospital, Ministry of Health Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors and Academy for Advanced Interdisciplinary Studies, Peking University [2]Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry,Chinese Academy of Sciences

出　　处：《Science China Chemistry》2017年第10期1310-1317,共8页中国科学（化学英文版）

基　　金：supported by the National Basic Research Program of China (2013CB933701);the National Natural Science Foundation of China (81530009, 21127901, 91213305);Chinese Academy of Science

摘　　要：Stimulation of G protein-coupled receptors(GPCRs) can lead to the transactivation of the epidermal growth factor receptors(EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach.We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor(β2-AR) by isoproterenol(ISO). We further proved thatβ2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.Stimulation of G protein-coupled receptors（GPCRs） can lead to the transactivation of the epidermal growth factor receptors（EGFR）. The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach.We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor（β2-AR） by isoproterenol（ISO）. We further proved thatβ2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.

关 键 词：transactivation epidermal growth factor receptor（EGFR） β2-adrenergic receptor（β2-AR） single molecule imaging 

分 类 号：R363[医药卫生—病理学]