Src介导骨桥蛋白诱导的血管平滑肌细胞黏附和迁移过程  

Src Mediates the Adhesion and Migration of Vascular Smooth Muscle Cells Induced by Osteopontin

作　　者：李菁菁[1] 温进坤[1] 韩梅[1] 

机构地区：[1]河北医科大学基础医学研究所,河北省医学生物技术重点实验室,石家庄050017

出　　处：《细胞生物学杂志》2006年第5期757-762,共6页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(No.30570661);国家科技部基础研究重大项目前期研究专项项目(No.2005CCA03100);河北省自然科学基金(No.303455);高等学校博士学科点专项科研基金(No.20040089018)资助~~

摘　　要：为阐明酪氨酸激酶Src在整合素被骨桥蛋白(OPN)激活所触发的细胞黏附和迁移信号途径中所起的作用,应用Src特异性抑制剂PP2阻断Src,观察OPN诱导的血管平滑肌细胞(VSMC)黏附和迁移活性的改变,并利用免疫沉淀检查PP2对整合素下游信号分子黏着斑激酶(FAK)和整合素偶联激酶(ILK)磷酸化及其相互作用的影响。结果显示,PP2可明显抑制OPN诱导的VSMC黏附和伤口愈合(黏附和迁移活性分别为对照组的76.6%和33.8%);OPN可显著诱导FAK磷酸化(磷酸化水平达对照组的1.9倍),促进ILK去磷酸化,并使FAK与ILK的结合减少(降至对照组的46.4%)。10μmol/LPP2可明显抑制OPN诱导的FAK磷酸化、拮抗OPN诱导对ILK的去磷酸化作用、促进FAK与ILK之间的结合。研究结果表明,Src作为OPN-整合素-FAK信号途径中的信号分子,通过影响FAK和ILK的磷酸化以及两者之间的相互作用来调节VSMC的黏附和迁移活性。To investigate the roles of tyrosine kinase Src and related signaling molecules in regulating the adhesion and migration of vascular smooth muscle cells （VSMCs）, the adhesion and migration of VSMCs were induced by osteoponin （OPN）, and the effect of Src specific inhibitor PP2 on VSMC adhesion and migration as well as focal adhesion kinase （FAK） and integrin-linked kinase （ILK） was studied. The results showed that the adhesion and migration of VSMCs induced by OPN were decreased to 76.6% and 33.8% of control （P〈0.05）, respectively, after the cells were pre-treated with PP2 for 1 h. The level of phosphorylated FAK increased about 1.9 times after VSMCs were treated with OPN, compared with that of control. The immunoprecipitation and Western blotting showed OPN stimulation induced ILK dephosphorylation and inhibited the association of FAK with ILK, which was reduced to 46.4% of control. PP2 significantly inhibited the phosphorylation of FAK, antagonized ILK dephosphorylation induced by OPN and promoted the association of FAK with ILK. These results suggest that Src regulates the adhesion and migration of VSMCs through affecting the phosphorylation of FAK and dephosphorylation of ILK, and that Src may be involved in OPN-integrin-FAK signaling pathway.

关 键 词：血管平滑肌细胞 SRC 黏附 迁移 黏着斑激酶 

分 类 号：Q25[生物学—细胞生物学]