CONTRASTING ROLES FOR INTEGRIN-BETA(1) AND INTEGRIN-BETA(5) CYTOPLASMIC DOMAINS IN SUBCELLULAR-LOCALIZATION, CELL-PROLIFERATION, AND CELL-MIGRATION

To carry out a detailed comparison of the roles of integrin beta1 and beta5 cytoplasmic domains, we expressed both wild type beta1 and chimeric beta1/5 constructs in CHO cells. In the latter, the cytoplasmic domain of beta1 was replaced with that of beta5. The human beta1 and beta1/5 constructs appeared at similar levels at the cell surface (mostly as alpha5beta1 heterodimers) and contributed equally to CHO cell adhesion to fibronectin. However, beta1 but not beta1/5 localized to focal adhesion-like structures when CHO cells were spread on fibronectin. Furthermore, only the beta1-CHO cells showed increased proliferation in response to fibronectin plus an integrin-activating anti-beta1 antibody, and showed increased appearance of P-12-labeled protein (p90) that correlated with proliferation. In sharp contrast, the beta1/5-CHO cells were notably more migratory than beta1-CHO cells in a transwell haptotactic migration assay. These results indicate that the beta1 and beta5 integrin subunit cytoplasmic domains can translate similar adhesive information into highly contrasting subsequent events. Thus, we have established that ''inside-out'' and ''outside-in'' integrin signaling pathways are regulated by fundamentally distinct mechanisms. In addition, we suggest that the same properties of the beta1 cytoplasmic domain that promote recruitment to visible focal adhesion-like structures may also be conducive to cell proliferation. Conversely, the properties of the beta5 tail that make it less likely to localize into focal adhesion-like structures may contribute to enhanced cell migration.