Shi Xiaohua, Ma Yan-Qing, Tu Yizeng, Chen Ka, Wu Shan, Fukuda Koichi, Qin Jun, Plow Edward F, Wu Chuanyue
Department of Pathology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
J Biol Chem. 2007 Jul 13;282(28):20455-66. doi: 10.1074/jbc.M611680200. Epub 2007 May 18.
Integrin-mediated cell-matrix adhesion plays an important role in control of cell behavior. We report here that MIG-2, a widely expressed focal adhesion protein, interacts with beta1 and beta3 integrin cytoplasmic domains. Integrin binding is mediated by a single site within the MIG-2 FERM domain. Functionally, the MIG-2/integrin interaction recruits MIG-2 to focal adhesions. Furthermore, using alphaIIbbeta3 integrin-expressing Chinese hamster ovary cells, a well described model system for integrin activation, we show that MIG-2 promotes integrin activation and enhances cell-extracellular matrix adhesion. Although MIG-2 is expressed in many cell types, it is deficient in certain colon cancer cells. Expression of MIG-2, but not of an integrin binding-defective MIG-2 mutant, in MIG-2-null colon cancer cells strengthened cell-matrix adhesion, promoted focal adhesion formation, and reduced cell motility. These results suggest that the MIG-2/integrin interaction is an important element in the cellular control of integrin-mediated cell-matrix adhesion and that loss of this interaction likely contributes to high motility of colon cancer cells.
整合素介导的细胞与基质黏附在控制细胞行为中起重要作用。我们在此报告，MIG-2是一种广泛表达的黏着斑蛋白，它与β1和β3整合素的胞质结构域相互作用。整合素结合由MIG-2 FERM结构域内的单个位点介导。在功能上，MIG-2与整合素的相互作用将MIG-2募集到黏着斑。此外，利用表达αIIbβ3整合素的中国仓鼠卵巢细胞（一种用于整合素激活的已充分描述的模型系统），我们表明MIG-2促进整合素激活并增强细胞与细胞外基质的黏附。虽然MIG-2在许多细胞类型中表达，但在某些结肠癌细胞中缺乏。在MIG-2缺失的结肠癌细胞中表达MIG-2而非整合素结合缺陷的MIG-2突变体，可增强细胞与基质的黏附，促进黏着斑形成，并降低细胞运动性。这些结果表明，MIG-2与整合素的相互作用是细胞控制整合素介导的细胞与基质黏附的一个重要因素，这种相互作用的丧失可能导致结肠癌细胞的高运动性。
