Substrate specificity of tissue-type and urokinase-type plasminogen activators.
Recent studies suggest that plasminogen activators not only hydrolyse a specific arginine-valine bond in plasminogen, but may also cleave other proteins such as fibronectin. We studied the substrate specificity, particularly the preference for arginyl over lysyl peptide bonds, of tissue-type plasminogen activator (t-PA) as well as of two-chain urokinase-type plasminogen activator (u-PA). The arginine/lysine preference was determined with three pairs of tripeptidyl-p-nitroanilide substrates having either arginine or lysine in the P1 position and varied from 5.2 to 14.1 for u-PA and from 55.6 to 99.8 for t-PA. It was concluded that both t-PA and u-PA preferred arginyl to lysyl peptide bonds. However, u-PA had a significantly lower arginine/lysine preference than t-PA, indicating that u-PA represents a less specific proteinase. This may point to functions of u-PA other than plasminogen activation, which involve cleavage of lysyl bonds.
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Gaubius Institute TNO, Leiden, The Netherlands.
Groeneveld
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D000595:Amino Acid Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004792:Enzyme Precursors / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008545:Melanoma / Q000201:enzymology; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity; D010959:Tissue Plasminogen Activator / Q000302:isolation & purification / Q000378:metabolism* / Q000652:urine; D014407:Tumor Cells, Cultured / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000302:isolation & purification / Q000378:metabolism*
D004792:Enzyme Precursors; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator