磷脂酰肌醇3-激酶γ/δ与炎症相关疾病  

Phosphatidylinositol 3-kinase γ/δ in Inflammatory Diseases

作　　者：樊帆 卢晓云[1] 马建岗[1] 

机构地区：[1]生物医学信息工程教育部重点实验室、西安交通大学生命科学与技术学院,西安710049

出　　处：《中国生物化学与分子生物学报》2014年第10期963-972,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81172170,No.81371288);陕西省科学技术研究发展计划项目(No.2013KW32-04);西安交通大学中央高校基本科研业务费项目(No.xjj2011097)~~

摘　　要：磷脂酰肌醇3-激酶(PI3K)是一类脂质与蛋白激酶家族,其主要通过在磷脂酰肌醇的肌醇环三位进行磷酸化产生胞内重要的第二信使——磷脂酰肌醇-3,4,5-三磷酸(phosphatidyl inositol 3,4,5-trisphosphate,PIP3)而发挥作用.磷脂酰肌醇3-激酶γ/δ(PI3Kγ/δ)是I类PI3K家族中的成员,其主要表达于免疫相关细胞中,这2种PI3K亚型参与先天性与获得性免疫应答.因此,PI3Kγ/PI3Kδ被视为因免疫反应调控异常导致的炎症疾病的治疗药物靶点.目前,利用特异性抑制剂靶向干预PI3Kγ和/或PI3Kδ,成为炎症相关疾病治疗的新策略.本文简介了PI3Kγ与PI3Kδ在不同类型免疫细胞中的功能;并就采用小分子特异性抑制剂,靶向抑制PI3Kγ和/或PI3Kδ在各类炎症相关疾病中的治疗作用和效果进行综述.PI3Ks are a class of kinases that produce PIP3,an important second messenger,by phosphorylating phosphoinositide at the D3 position. PI3Kγ and PI3Kδ are members of class I PI3Ks;and mainly expressed in immune cells playing an essential role in both innate and acquired immune responses. PI3Kγ and PI3Kδ are considered as the therapeutic target for the intervention of inflammatory diseases. Currently,the development of novel PI3 K inhibitors targeting to PI3Kγ and /or PI3Kδ with pharmacological effects offers a promising strategies for the treatment of inflammatory diseases. This review briefly introduced PI3Kγ /δ functions in different immune cell types（ leukocyte,macrophage and lymphocyte etc.）. The latest progress of the therapeutic effect of various inflammatory diseases（ autoimmune diseases,respiratory diseases,cardiovascular diseases and systemic inflammatory diseases,etc.） was selectively discussed,particularly the targeting of PI3Kγ and /or PI3Kδ with small molecules.

关 键 词：磷脂酰肌醇3-激酶γ/δ 免疫细胞 炎症相关疾病 

分 类 号：Q74[生物学—分子生物学]