IDENTIFICATION OF THE UROKINASE RECEPTOR AS ALL ADHESION RECEPTOR FORVITRONECTIN

Urokinase receptors, expressed on surfaces of many cell types, focus t o the pericellular space plasminogen-dependent proteolysis important i n matrix remodeling and cell movement. We now report that the urokinas e receptor (uPAR) is also a high affinity (K-d < 30 nar) receptor for vitronectin. Recombinant uPAR binds vitronectin in the absence of urok inase, but vitronectin binding is promoted by concurrent receptor bind ing of either urokinase or fragments thereof containing its uPAR bindi ng domain. Stable epithelial cell transfectants expressing membrane-an chored uPAR, but not cells expressing soluble uPAR,become strongly adh esive with altered morphology in the absence of urokinase. These obser vations identify a new class of vitronectin receptor and imply a duali ty in function for the receptor that intrinsically links matrix adhesi on to regulation of protease activity. Increases in urokinase receptor expression known to be associated with cellular activation and malign ant transformation could modulate cellular trafficking and function by promoting attachment to vitronectin.