REGULATION OF INTEGRIN FUNCTION BY THE UROKINASE RECEPTOR

Integrin function is central to inflammation, immunity, and tumor prog ression. The urokinase-type plasminogen activator receptor (uPAR) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand bi nding site on uPAR. Interaction of soluble uPAR with the active confor mer of integrins mimicked the inhibitory effects of membrane uPAR. Bot h uPAR-mediated adhesion and altered integrin function were blocked by a peptide that bound to uPAR and disrupted complexes. These data prov ide a paradigm for regulation of integrins in which a nonintegrin memb rane receptor interacts with and modifies the function of activated in tegrins.