Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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CD18 Antigens / metabolism
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Cell Adhesion*
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Cell Line
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Fibronectins / metabolism
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Glycosylphosphatidylinositols / metabolism
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Humans
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Integrin beta1 / metabolism
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Integrins / metabolism
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Integrins / physiology*
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Ligands
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Molecular Sequence Data
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Receptors, Cell Surface / metabolism*
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Receptors, Cytoadhesin / metabolism*
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Receptors, Urokinase Plasminogen Activator
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Recombinant Fusion Proteins / metabolism
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Transfection
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Urokinase-Type Plasminogen Activator / metabolism
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Vitronectin / metabolism
Substances
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CD18 Antigens
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Fibronectins
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Glycosylphosphatidylinositols
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Integrin beta1
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Integrins
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Ligands
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PLAUR protein, human
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Receptors, Cell Surface
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Receptors, Cytoadhesin
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Receptors, Urokinase Plasminogen Activator
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Recombinant Fusion Proteins
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Vitronectin
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Urokinase-Type Plasminogen Activator