Regulation of integrin function by the urokinase receptor.
Integrin function is central to inflammation, immunity, and tumor progression. 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 binding site on uPAR. Interaction of soluble uPAR with the active conformer of integrins mimicked the inhibitory effects of membrane uPAR. Both uPAR-mediated adhesion and altered integrin function were blocked by a peptide that bound to uPAR and disrupted complexes. These data provide a paradigm for regulation of integrins in which a nonintegrin membrane receptor interacts with and modifies the function of activated integrins.
Wei
Y
Y
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Lukashev
M
M
Simon
D I
DI
Bodary
S C
SC
Rosenberg
S
S
Doyle
M V
MV
Chapman
H A
HA
D000595:Amino Acid Sequence; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D005353:Fibronectins / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
D018821:CD18 Antigens; D005353:Fibronectins; D017261:Glycosylphosphatidylinositols; D019012:Integrin beta1; D016023:Integrins; D008024:Ligands; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D016024:Receptors, Cytoadhesin; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; D014568:Urokinase-Type Plasminogen Activator