REGULATION OF CELL-MIGRATION BY THE INTEGRIN BETA-SUBUNIT ECTODOMAIN

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 b eta 5, respectively, enabling them to adhere to vitronectin yet only a lpha 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 vitronecti n. To identify structural regions in beta 3 or beta 5 that account for these distinct biological properties, CS-1 cells were transfected wit h one of two chimeric beta subunit proteins, in which the ecto- and cy toplasmic 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 expressi ng cells spread and migrate on vitronectin while cells expressing alph a v beta 5/3 do not unless they are exposed to cytokine. These finding s suggest that the distinct migratory properties mediated by integrins alpha v beta 3 and alpha v beta 5 and their response to cytokine acti vation is determined by a sequence(s) within the ectodomain of the int egrin beta subunit.