Yebra M, Filardo E J, Bayna E M, Kawahara E, Becker J C, Cheresh D A
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Mol Biol Cell. 1995 Jul;6(7):841-50. doi: 10.1091/mbc.6.7.841.
Integrin alpha v beta 5 promotes FG carcinoma cell adhesion to vitronectin yet requires protein kinase C (PKC) activation for migration on this ligand. Here we report that this PKC-dependent cell motility event requires NF-kappaB-dependent transcription. Specifically, a component within nuclear extracts prepared from PKC-stimulated FG cells exhibited a significant increase in binding activity to a synthetic oligonucleotide containing a consensus kappa B sequence. These nuclear DNA-binding complexes were shown to be comprised of p65 and p50 NF-kappaB/rel family members and appeared functionally active because they promoted transcription of a reporter construct containing a kappa B site. The NF-kappa B activation event was directly linked to the alpha v beta 5 motility response because the NF-kappa B-binding oligonucleotide, when introduced into FG cells, inhibited cell migration on vitronectin but not on collagen and had no effect on cell adhesion to either ligand. These results suggest that the detected DNA-binding complexes interact with kappa B transcriptional elements to regulate gene expression required for alpha v beta 5-dependent cell motility on vitronectin.
整合素αvβ5促进FG癌细胞与玻连蛋白的黏附，但在该配体上迁移时需要蛋白激酶C（PKC）激活。在此我们报告，这种依赖PKC的细胞运动事件需要依赖核因子κB（NF-κB）的转录。具体而言，从PKC刺激的FG细胞制备的核提取物中的一种成分，与含有κB共有序列的合成寡核苷酸的结合活性显著增加。这些核DNA结合复合物显示由p65和p50 NF-κB/rel家族成员组成，并且似乎具有功能活性，因为它们促进了含有κB位点的报告构建体的转录。NF-κB激活事件与αvβ5运动反应直接相关，因为当将NF-κB结合寡核苷酸导入FG细胞时，它会抑制细胞在玻连蛋白上的迁移，但不影响在胶原蛋白上的迁移，并且对细胞与这两种配体的黏附没有影响。这些结果表明，检测到的DNA结合复合物与κB转录元件相互作用，以调节αvβ5依赖的细胞在玻连蛋白上运动所需的基因表达。
