EXPRESSION OF BETA-1B INTEGRIN ISOFORM IN CHO CELLS RESULTS IN A DOMINANT-NEGATIVE EFFECT ON CELL-ADHESION AND MOTILITY

The integrin subunit beta 1B, a beta 1 isoform with a unique sequence at the cytoplasmic domain, forms heterodimers with integrin ct chains and binds fibronectin, but it does not localize to focal adhesion site s (Balzac, F., A. Belkin, V. Koteliansky, Y. Balabanow, F. Altruda, L. Silengo, and G. Tarone. 1993. J. Cell Biol. 121:171-178). Here we ana lyze the functional properties of human beta 1B by expressing it in ha mster CHO cells. When stimulated by specific antibodies, beta 1B does not trigger tyrosine phosphorylation of a 125-kD cytosolic protein, an intracellular signal ing pathway that is activated both by the endoge nous hamster or the transfected human beta 1A. Moreover, expression of beta 1B results in reduced spreading on fibronectin and laminin, but not on vitronectin. Expression of beta 1B also results in severe reduc tion of eel motility in the Boyden chamber assay. Reduced cell spreadi ng and motility could not be accounted for by preferential association of beta 1B with a given integrin at subunit. These data, together wit h our previous results, indicate that beta 1B interferes with beta 1A function when expressed in CHO cells resulting in a dominant negative effect on cell adhesion and migration.