A linear amino acid sequence involved in the interaction of t-PA with its endothelial cell receptor.
Endothelial cell receptors for tissue plasminogen activator (t-PA) have been demonstrated recently, and we have sought to identify a region of the t-PA molecule involved in its interaction with these receptors on human umbilical vein endothelial cells. Of three monoclonal antibodies against various regions of t-PA, one directed against the finger region inhibited 125I-t-PA binding to the cells. Synthetic peptides corresponding in amino acid sequences to segments from within the finger region were constructed, and one of these inhibited t-PA binding. This peptide corresponded to residues 7 through 17 of t-PA. The inhibition by this peptide was specific as other peptides from the finger region were inactive. The inhibitory peptide also did not affect the binding of another fibrinolytic ligand, urokinase, to the cells. Although a role for other regions of t-PA in binding to endothelial cells cannot be excluded, the results implicate a short span of linear amino acid sequence within the finger region in the interaction of t-PA with endothelial cells.
Beebe
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DP
Center for Drugs and Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD.
Miles
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LA
Plow
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D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D004730:Endothelium, Vascular / Q000378:metabolism*; D000939:Epitopes; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D009842:Oligopeptides; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005337:Fibrin; D010959:Tissue Plasminogen Activator