鲤鱼SOCS1-3在JAK-STAT信号通路中的调节作用及其机制研究

JAK-STAT pathways are the main intracellular signaling pathways for many cytokines and hormones. In mammals, the suppressors of cytokine signaling (SOCSs) regulate a lot of important physiological activities and pathological process through JAK/STAT system. However, functions of fish SOCS molecules are still unclear and under the circumstance it is hindered for us to understand thoroughly the physiological mechanisms of immune response, growth and development, and metabolism regulation in fish. In the present study, we will choose common carp, one of important freshwater commercial fish species, as the research object, and at the first time investigate systematically on the tissue distribution and sub-cellular localization of JAKs/STATs/SOCS1-3 (SOCS-1,SOCS-2, and SOCS-3), expression regulation of JAK and STAT genes by SOCS1-3, cross-regulation of SOCS1-3, JAK types to which SOCS1-3 bind respectively, and the molecular mechanism of JAK/SOCS interaction in bony fish, by using various technical means derived from molecular biology,cytobiology,biochemistry, and immunolgy. And then the roles and the regulatory functions of bony fish SOCS1-3 in JAK-STAT pathways will be explored. The completion of the proposed research will lay the foundation for thorough investigation of the regulatory function of fish SOCSs in the JAK/STAT-dependent signaling pathways of GH and IFN, and mechanism of action.

JAK-STAT途径是众多细胞因子和激素分子最主要的胞内信号通路，在哺乳动物中，细胞信号传导抑制因子（SOCS）通过作用于JAK/STAT系统来调控许多重要的生理和病理过程。但鱼类SOCS的功能尚缺乏了解，这极大地阻碍了对鱼类免疫、生长发育和代谢调控等方面的充分认识。本项目将以我国重要淡水经济鱼类－鲤鱼为对象，结合各种细胞、分子、生化和免疫学技术手段，首次系统地研究鱼类JAKs/STATs/SOCS1-3（SOCS-1、SOCS-2和SOCS-3）的组织分布、亚细胞定位特征，SOCS1-3对JAKs、STATs表达的调节，SOCS1-3的交叉调控关系、各自结合的JAK类型及其与JAK相互作用的机制。探讨鱼类SOCS1-3各自在JAK-STAT信号通路中的角色定位和调节功能，为深入解析鱼类SOCSs在依赖JAK-STAT途径的GH和IFN信号传导通路中的调控功能和作用机制奠定基础。

JAK-STAT途径是众多细胞因子和激素分子最主要的胞内信号通路，在哺乳动物中，细胞信号传导抑制因子（SOCS）通过作用于JAK/STAT系统来调控许多重要的生理和病理过程。但鱼类SOCS的功能尚缺乏了解，这极大地阻碍了对鱼类免疫、生长发育和代谢调控等方面的充分认识。本项目以我国重要淡水经济鱼类－鲤鱼为对象，结合各种细胞、分子、生化和免疫学技术手段，首次系统地研究鱼类JAKs/STATs/SOCS1-3（SOCS-1、SOCS-2和SOCS-3）的组织分布、细胞定位特征，SOCS1-3对JAKs、STATs表达的调节，SOCS1-3的交叉相互调控关系、各自结合的JAK类型及其与JAK相互作用的机制。探讨鱼类SOCS1-3在JAK-STAT信号通路中的角色和调节功能，为深入解析鱼类SOCSs对依赖JAK-STAT途径的GH和IFN信号传导的调控功能和作用机制奠定基础。