流行病学调查显示过敏性疾病的发病率高达15-30%，已成为严重影响人类健康的全球性疾病，被世界卫生组织列为本世纪重点防治的三大疾病之一。作为细胞信号通路主干枢纽蛋白的C-Raf激酶，通过与其结合蛋白相互作用，调控免疫细胞在过敏反应发生过程中的作用，但尚不了解C-Raf对过敏反应最直接的效应细胞肥大细胞功能的影响。本项目拟通过干扰肥大细胞C-Raf的表达来研究其对肥大细胞脱颗粒及炎症因子生成与释放的作用，同时观察不同状态下肥大细胞中C-Raf的活性及C-Raf结合蛋白谱的变化，来研究C-Raf及其结合蛋白对肥大细胞功能的影响。我们前期研究结果表明过敏原蛋白可以有效地活化肥大细胞，但其具体作用机制尚不清楚（Molecular & Cellular Proteomics 2013）。通过该研究阐述C-Raf及其结合蛋白对肥大细胞功能调控的作用机制，为过敏反应性疾病的诊治提供理论依据和潜在的靶标。

Epidemiologic survey have shown that the prevalence of allergic diseases in the world population is as high as 15-30%, it becomes a global health problem endangering human health, and is regarded as one of three major diseases by WHO (World Health Organization) with emphasis on their prevention and treatment in this century. C-Raf kinase is the key knot protein of C-Raf-MEK-MAPK signaling pathway which is at the heart of signaling networks. Through interacting with numerous its binding proteins, C-Raf kinase efficiently regulates the functions of dendritic cells, Th2 cells, and B cells in the process of allergic reactions. In this project, in order to find out the effect of C-Raf kinase on mast cells functions and the interaction of C-Raf-binding proteins with C-Raf, we will study the influence of C-Raf with different expression levels on mast cells activation, the expression and release of inflammatory cytokines and determine the change of C-Raf kinase activity and the spectrum of C-Raf-binding proteins in different states of mast cells (resting and activation states). In our previous study, it has been shown that different kinds of allergens can efficiently activate immune cells involved in allergies such as mast cells, but the mechanism is unclear (Molecular & Cellular Proteomics 2013). In this project, we will define the mechanism by which C-Raf kinase and its binding proteins regulate mast cells functions in the process of allergic reaction, and provide theoretical basis and potential targets for prevention and treatment of allergic diseases.