Filardo E J, Deming S L, Cheresh D A
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
J Cell Sci. 1996 Jun;109 ( Pt 6):1615-22. doi: 10.1242/jcs.109.6.1615.
CS-1 melanoma cells transfected with cDNAs encoding either the beta 3 or beta 5 integrin subunit protein express alpha v beta 3 or alpha v beta 5, respectively, enabling them to adhere to vitronectin yet only alpha v beta 3 promotes cell spreading and migration on this substrate. Following exposure to insulin or insulin-like growth factor, alpha v beta 5-expressing CS-1 cells gain the ability to migrate on vitronectin. To identify structural regions in beta 3 or beta 5 that account for these distinct biological properties, CS-1 cells were transfected with one of two chimeric beta subunit proteins, in which the ecto- and cytoplasmic domains of beta 3 and beta 5 were exchanged (termed alpha v beta 3/5 or alpha v beta 5/3). Surprisingly, alpha v beta 3/5 expressing cells spread and migrate on vitronectin while cells expressing alpha v beta 5/3 do not unless they are exposed to cytokine. These findings suggest that the distinct migratory properties mediated by integrins alpha v beta 3 and alpha v beta 5 and their response to cytokine activation is determined by a sequence(s) within the ectodomain of the integrin beta subunit.
用编码β3或β5整合素亚基蛋白的cDNA转染的CS - 1黑色素瘤细胞分别表达αvβ3或αvβ5，使它们能够黏附于玻连蛋白，但只有αvβ3能促进细胞在该底物上的铺展和迁移。在暴露于胰岛素或胰岛素样生长因子后，表达αvβ5的CS - 1细胞获得了在玻连蛋白上迁移的能力。为了确定β3或β5中负责这些不同生物学特性的结构区域，用两种嵌合β亚基蛋白之一转染CS - 1细胞，其中β3和β5的胞外和胞质结构域进行了交换（称为αvβ3/5或αvβ5/3）。令人惊讶的是，表达αvβ3/5的细胞在玻连蛋白上铺展并迁移，而表达αvβ5/3的细胞则不会，除非它们暴露于细胞因子。这些发现表明，整合素αvβ3和αvβ5介导的不同迁移特性及其对细胞因子激活的反应是由整合素β亚基胞外结构域内的一个或多个序列决定的。
