FAK通过和EGFR的相互作用调节MAPK和Akt之间的相对平衡  

FAK Regulates the Balance between MAPK and Akt Signal Pathways through Interaction with EGFR

作　　者：李永林[1] 蔡永[2] 刘先菊[3] R.M.Lafranie 沈洁[3] 王嫣[3] 张璐[3] 董伟[3] 张扬清[3] 祝梅香[3] 张连峰[3] 

机构地区：[1]中国协和医科大学神经外科,北京100730 [2]北京市肿瘤医院放射科 [3]中国医学科学院中国协和医科大学实验动物研究所遗传中心,北京100021 [4]Division of Tumor Biology,Northern Ontario Regional Cancer Center,Ontario,P3E,551,Canada

出　　处：《中国实验动物学报》2005年第4期193-199,F0005,共8页Acta Laboratorium Animalis Scientia Sinica

摘　　要：目的研究上皮生长因子受体和FAK的相互作用以及对下游信号的影响。方法建立聚集粘连激酶(FAK)缺失突变和绿色荧光蛋白(GFP)融合基因del1-693FAK-GFP、del1-100FAK-GFP和FAK-GFP稳定表达细胞系。结果同野生型FAK-GFP相比,N-端1-100氨基酸残基的缺失突变体,缺失1-693氨基酸残基的突变体结合在黏附点的能力被完全抑制。应用等电聚焦和SDS-PAGE双向电泳证明,EGF和纤维连接蛋白诱导FAK磷酸化的位点不同,进一步证实del1-693FAK-GFP、del1-100FAK-GFP,抑制MAPK的磷酸化,增强Akt的磷酸化;而FAK-GFP增强MAPK磷酸化,抑制Akt磷酸化。结论FAK通过和EGFR的相互作用调节MAPK和Akt之间的相对平衡。Objective Members of the epidermal growth factor （EGF） family of ligands and their receptors regulate migration and growth of intestinal epithelial cells： integrins, the immunoglobulin superfamily, selectins and cadherins. Each family is composed of a number of constitutional members. These cell adhesion molecules mediate the process of cellular adhesion to either the extracellular matrix （ECM） or initiate cell-cell adhesion. Focal adhesion kinase （FAK） is a major mediator of integrin signaling pathway. In this paper, the interaction between FAK and EGFR, and the regulation of FAK on the EGFR signaling pathway was studied. Methods Cell lines expressing del 1-693FAK-GFP, dcl 1-100FAK-GFP and FAK-GFP were used. The deletion mutants of FAK, del 1-693FAK-GFP and del 1-100FAK-GFP lost the ability to recruitment to adhesion sites. PI electrophoresis and Western blot analysis were applied. Results PI electrophoresis analysis indicated that the phosphorylation of FAK was regulated by EGF stimulation. Western blot analysis showed that expression of del 1-693FAK-GFP and del 1-100FAK- GFP inhibited the phosphorylation of MAPK. However, FAK-GFP enhanced the phosphorylation of MAPK and inhibited the phosphorylation of Akt. Conclusion The results suggested that FAK regulates the balance between MAPK and Akt signal pathways through interaction with EGFR.

关 键 词：受体 表皮生长因子 整粘蛋白 MAPK AKT 

分 类 号：R349.51[医药卫生—基础医学]