表皮生长因子受体结合蛋白及其在肿瘤治疗中的前景  

Regulation on EGFR Function Via Its Interacting Proteins and Its Potential Application

作　　者：郑君芳[1] 陈慧敏[1] 贺俊崎[1] 

机构地区：[1]首都医科大学生物化学与分子生物学系,北京100069

出　　处：《生理科学进展》2013年第6期403-408,共6页Progress in Physiological Sciences

基　　金：国家自然科学基金(30900247);北京市属高等学校高层次人才引进与培养计划项目(CIT&TCD201304187);北京市教委面上项目(KM201110025002);北京市科技新星计划B类(2008B58);北京市优秀人才培养资助项目(2010D005018000012);教育部留学回国人员科研启动基金资助项目(第42批)资助课题

摘　　要：表皮生长因子受体(epidermal growth factor receptor,EGFR)在肿瘤形成及转移中均起重要作用。EGFR抑制剂可有效治疗癌症,但存在皮肤毒性等多种副作用,不利于长期使用。EGFR相互作用蛋白可调节EGFR信号通路,其表达改变也能导致肿瘤形成,若将其作为靶点研制药物,可有效改善治疗结果、提高病人生活质量,故对EGFR相互作用蛋白的研究具有重要的临床意义。EGFR具有众多的相互作用蛋白,其中B1R促进EGFR所介导的Erk/MAPK信号激活,而PTPN12、Kek1、CEACAM1、NHERF对Erk/MAPK信号通路起抑制作用;CaM可通过结合并改变EGFR近膜区的电性调节PI3K/Akt及PLC-γ/PKC信号。通常认为STAT1、STAT5b可被EGFR激活,但最近研究表明EGFR还存在抑制STAT活性的结构域。LRIG1、ACK1可促进EGFR的内化和降解,而NHERF、HIP1对EGFR的内化和降解起抑制作用。本文对多种EGFR相互作用蛋白及其与EGFR的结合位点、对EGFR信号通路和EGFR相关功能的调节作用进行综述。Epidermal growth factor receptor( EGFR) is imptortant for cell activities,oncogenesis and cell migration,and EGFR inhibitor can treat cancer efficiently,but its side effects,for example,in skin, limited its usage. On the other hand,EGFR interacting proteins may also lead to oncogenesis and its interacting protein as drug targets can avoid cutaneous side effect,which implies possibly a better outcome and life quality of cancer patients. For the multiple EGFR interaction proteins,B1R enhances Erk / MAPK signaling,while PTPN12,Kek1,CEACAM1 and NHERF repress Erk / MAPK signaling. CaM may alter charge of EGFR juxamembrane domain and regulate activation of PI3K / Akt and PLC-γ / PKC. STAT1,STAT5b are widely thought to be activated by EGFR,while there is unexpectedly inhibiting sequence within EGFR to repress the activity of STATs. LRIG1 and ACK1 enhance the internalization and degration of EGFR,while NHERF and HIP1 repress it. In this article,proteins interacting with EGFR, their interacting sites and their regulation on EGFR signal transduction will be reviewed.

关 键 词：表皮生长因子受体(EGFR) 相互作用蛋白 肿瘤 信号通路 

分 类 号：R730[医药卫生—肿瘤]