De Novo expression of the Integrin α5β1 regulates αvβ3-mediated adhesion and migration on fibrinogen

Recent evidence demonstrates that interactions between different integrins that are present on the cell surface can strongly influence the adhesive function of individual receptors. In this report, we show that Chinese hamster ovary cells that express the integrin alpha(v)beta(3) in the absence of alpha(5)beta(1) demonstrate increased adhesion and migration on fibrinogen. Furthermore, alpha(v)beta(3)-mediated adhesion to fibrinogen is not augmented by the soluble agonist, MnCl2, suggesting that alpha(v)beta(3) exists in a higher affinity state in these cells. De novo expression of wild-type alpha(5)beta(1) negatively regulates alpha(v)beta(3)-mediated adhesion and migration. This effect is not seen with expression of a chimeric alpha(5)beta(1) integrin in which the cytoplasmic portion of the alpha(5) integrin subunit is replaced by the cytoplasmic portion of the alpha(4) integrin. In addition, it does not require ligation of alpha(5)beta(1) by fibronectin. Cells that express a constitutively active beta(3) integrin that contains a point mutation in the conserved membrane proximal region of the cytoplasmic tail, D723R, are resistant to the effect of alpha(5)beta(1) expression. These data provide additional evidence of "cross-talk" between the integrins alpha(5)beta(1) and alpha(v)beta(3), and support the idea that alpha(5)beta(1) regulates alpha(v)beta(3)-mediated ligand binding. This provides a relevant biological mechanism whereby variations in alpha(5)beta(1) expression in vivo may modulate activation of alpha(v)beta(3) to influence its adhesive function.