Identification of the urokinase receptor as an adhesion receptor for vitronectin.
Urokinase receptors, expressed on surfaces of many cell types, focus to the pericellular space plasminogen-dependent proteolysis important in matrix remodeling and cell movement. We now report that the urokinase receptor (uPAR) is also a high affinity (Kd < 30 nM) receptor for vitronectin. Recombinant uPAR binds vitronectin in the absence of urokinase, but vitronectin binding is promoted by concurrent receptor binding of either urokinase or fragments thereof containing its uPAR binding domain. Stable epithelial cell transfectants expressing membrane-anchored uPAR, but not cells expressing soluble uPAR, become strongly adhesive with altered morphology in the absence of urokinase. These observations identify a new class of vitronectin receptor and imply a duality in function for the receptor that intrinsically links matrix adhesion to regulation of protease activity. Increases in urokinase receptor expression known to be associated with cellular activation and malignant transformation could modulate cellular trafficking and function by promoting attachment to vitronectin.
Wei
Y
Y
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Waltz
D A
DA
Rao
N
N
Drummond
R J
RJ
Rosenberg
S
S
Chapman
H A
HA
D000327:Adsorption; D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002478:Cells, Cultured; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin
D006023:Glycoproteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; D014568:Urokinase-Type Plasminogen Activator