剪接因子蛋白激酶SRPK1在肿瘤的发生发展过程中扮演重要角色，目前对其作用机制的研究主要集中在其对下游信号分子的选择性剪接调控上。本课题组新近发现，SRPK1能够激活PI3K/Akt信号通路核心组分Akt蛋白活性促进肝癌发生。进一步分析发现SRPK1和PI3K的p110α亚基存在相互作用和共定位，同时利用免疫共沉淀和质谱联用的方法筛选到一个和SRPK1相互作用的转录因子YBX-1，该因子能够被Akt磷酸化而发挥致癌作用。基于以上结果，我们设想PI3K/Akt信号转导通路可能介导了SRPK1的致癌作用。本项目拟继续深入研究SRPK1如何通过结合p110α而激活Akt，SRPK1与YBX-1的结合是否促进YBX-1的致癌效应以及这一结合是否受到PI3K/Akt信号调控。该项目的完成，将第一次阐明SRPK1促进肿瘤发生的一种不依赖于选择性剪接的新的分子机制，为筛选抗癌药物提供理论依据。

Splicing factor protein kinase SRPK1 plays an important role in tumor development and progression. Presently, most of studies on its molecular mechnism by which SRPK1 causes tumor are focused on the regulation of alternative splicing of downstream factors. Our initial research results indicated that SRPK1 could activate Akt, the core component of PI3K/Akt signaling. We further investigated its molecular mechanism and found the interaction and colocalization between SRPK1 and p110alpha. Moreover, we also identified a number of proteins interacting with SRPK1 by Co-IP and Mass spectrum. These interacting proteins include a transcription factor named YBX-1, which has been proved to be a substrate of Akt and acts as an oncogene. Taken together, we suggest that SRPK1 contributes to cancer development through PI3K/Akt signaling. In this project, we will further conduct research on the molecular mechanism by which SRPK1 kinase activates Akt and whether SRPK1 promotes YBX-1 activity by binding this factor. This project is expected to provide a novel mechanism for tumorigenesis independent of alternative splicing, and a theoretical basis for screening a new anti-tumor target.