Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy.
Urokinase receptors are distributed on surfaces of many cell types where they are thought to focus plasminogen-dependent proteolysis important to migration and tissue remodeling to the immediate pericellular space. In addition to its well characterized role in proteolysis, urokinase receptor binding per se promotes the adhesiveness of leukemic cell lines exposed to differentiating cytokines in vitro. We sought to determine if a serum or matrix component is involved in urokinase-dependent adhesion. We now report that cytokine-stimulated human myelomonocytic cells express a divalent cation- and Arg-Gly-Asp-independent high affinity receptor for urea-purified vitronectin (Kd < 10 nM). Soluble native vitronectin does not effectively bind to the receptor, while cellular adhesion was noted to both urea-purified and native vitronectin when adsorbed to plastic. The activity of this receptor is tightly coupled to urokinase receptor occupancy. Urokinase receptor binding thus induces selective and reversible cellular adhesion to the matrix form of vitronectin. Because transfer of vitronectin-bound plasminogen activator inhibitor type 1 to urokinase promotes rapid turnover of receptor-bound enzyme, these results illuminate a novel binding cycle by which urokinase receptor occupancy coordinately regulates cellular adhesiveness and pericellular proteolysis.
Waltz
D A
DA
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Chapman
H A
HA
D000230:Adenocarcinoma; D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D046508:Culture Techniques / Q000379:methods; D016207:Cytokines / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006023:Glycoproteins; D006801:Humans; D007951:Leukemia, Myeloid; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology; D019096:Vitronectin
D001798:Blood Proteins; D002413:Cations, Divalent; D016207:Cytokines; D006023:Glycoproteins; D009842:Oligopeptides; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta; D019096:Vitronectin; D004492:Edetic Acid; D014568:Urokinase-Type Plasminogen Activator