美国克利夫兰 MetroHealth医学中心Bingcheng Wang、阿克伦大学Adam W. Smith及纪念斯隆-凯特琳癌症中心Dimitar B. Nikolov研究组，合作的最新研究利用时间分辨活细胞光谱学揭示了Ephrin-A型受体2（EphA2）多聚体的组装过程。该研究于2023年11月16日发表于国际学术期刊《科学》杂志上。

研究人员使用时间分辨活细胞荧光光谱发现不含配体的EphA2在外显子区域两种分子相互作用的诱导下组装成多聚体。第一种类型是配体诱导的受体集群和肿瘤抑制信号传导所需的扩展对称相互作用，这种信号传导可抑制致癌因子ERK和Akt蛋白激酶的活性并抑制细胞迁移。

第二种类型是邻近受体N末端和膜近端结构域之间的不对称相互作用，其有利于致癌信号传导，促进体外迁移和体内肿瘤侵袭。该研究结果确定了诱导EphA2多聚体信号簇形成的分子相互作用，并表明EphA2组装决定了其在肿瘤发生过程中的对立功能。

据悉，EphA2是一种受体酪氨酸激酶，它既能启动配体依赖性肿瘤抑制信号，也能开启配体依赖性致癌信号。

附：英文原文

Title: Time-resolved live-cell spectroscopy reveals EphA2 multimeric assembly

Author: Xiaojun Shi, Ryan Lingerak, Cameron J. Herting, Yifan Ge, Soyeon Kim, Paul Toth, Wei Wang, Benjamin P. Brown, Jens Meiler, Khalid Sossey-Alaoui, Matthias Buck, Juha Himanen, Dolores Hambardzumyan, Dimitar B. Nikolov, Adam W. Smith, Bingcheng Wang

Issue&Volume: 2023-11-16

Abstract: Ephrin type-A receptor 2 (EphA2) is a receptor tyrosine kinase that initiates both ligand-dependent tumor suppressive and ligand-independent oncogenic signaling. We used time-resolved, live-cell fluorescence spectroscopy to show that the ligand-free EphA2 assembles into multimers driven by two types of intermolecular interactions in the ectodomain. The first type entails extended symmetric interactions required for ligand-induced receptor clustering and tumor-suppressive signaling that inhibits activity of the oncogenic ERK and Akt protein kinases and suppresses cell migration. The second type is an asymmetric interaction between the N terminus and the membrane proximal domain of the neighboring receptors, which supports oncogenic signaling and promotes migration in vitro and tumor invasiveness in vivo. Our results identify the molecular interactions driving the formation of the EphA2 multimeric signaling clusters and reveal the pivotal role of EphA2 assembly in dictating its opposing functions in oncogenesis.

DOI: adg5314

Source: https://www.science.org/doi/10.1126/science.adg5314