EPH受体是受体酪氨酸激酶中最大的一类亚家族，在神经细胞树突生长的路径选择、动静脉血管分化、肿瘤的发生、骨细胞的生长发育以及突触的稳态维持等生理过程中都发挥了非常重要的作用。目前对EPH受体SAM结构域介导的下游蛋白互作网络及其分子机制仍不清楚。在前期实验中，我们发现EPH受体与下游蛋白SAM-SAM互作存在很强的亚型特异性现象，而目前文献中关于EPH受体SAM-SAM互作的分子机制却不能很好地解释这一现象。因此，我们拟结合生物化学与结构生物学手段，对已知的EPH受体SAM-SAM互作的亚型特异性的结构基础进行深入解析，同时应用生物信息学与生物化学的方法寻找更多的互作蛋白并解析其复合物结构，从而系统地阐述它们互作的分子机制。最终，通过操纵这种互作的特异性，将为在不同亚型EPH受体之间进行信号通路切换和功能改变提供可能。

The EPH receptor family is the largest subfamily member of the receptor tyrosine kinases. It plays important roles in neuronal axon guidance, artery/venous differentiation, tumorigenesis, bone homeostasis and synaptogenesis, etc. Currently it still remains unclear how the EPH receptors use their SAM domains to organize the downstream interaction networks and what is the molecular mechanism of these SAM-SAM interactions. In our preliminary experiments, we found EPH family members can interact with their downstream effectors with clear isoform-dependent specificities, which can not be explained by the current EPH SAM-SAM interaction mechanisms. To solve this problem, we plan to utilize the biochemical and structural biology methods to study the structure basis of the specific SAM-SAM interactions between the known EPH/effector pairs . Furthermore, by using bioinformatics and biochemical tools, we want to explore more novel downstream effectors and systematically elaborate their molecular mechanisms. Finally, by manipulating these binding specificities, it will be possible to manually switch their functions and downstream signaling pathways among different EPH receptor isoforms.