Reversible interactions between plasminogen activators and plasminogen activator inhibitor-1

Biochim Biophys Acta. 1992 Dec 28;1160(3):325-34. doi: 10.1016/0167-4838(92)90095-u.


We have shown that the urokinase (UK) kringle domain contains a high-affinity plasminogen activator inhibitor-1 (PAI-1) binding site, responsible for the 10-fold faster complex formation between UK and PAI-1 than between PAI-1 and low-molecular-weight urokinase (LMWUK). Complex formation between UK and PAI-1, but not between LMWUK and PAI-1, was suppressed 10-fold in the presence of peptide U-107 derived from the UK kringle domain. Peptide U-373 derived from the UK catalytic domain slowed complex formation between UK and PAI-1 and also LMWUK and PAI-1. Inactivation of tissue-type plasminogen activator (tPA) by PAI-1 was slowed 10-fold in the presence of peptides derived from the tPA finger and kringle-2 domains. DFP-inactivated (DIP) UK and both forms of DIP-tPA inhibited PAI-1 binding to U-107 and to U-373 whereas single-chain urokinase-type PA (scuPA) was unable to compete with either peptide for PAI-1 binding. These data suggest that the reversible PAI-1 binding site in the UK A-chain plays a role in the rapid association with PAI-1 as important as those that reside in the tPA A-chain and that reversible PAI-1 binding sites are expressed on the surface of UK upon conversion from scuPA, in contrast to tPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Binding Sites
  • Cell Line
  • Fibrinolysin
  • Humans
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Molecular Structure
  • Plasminogen Activator Inhibitor 1 / chemistry*
  • Plasminogen Activator Inhibitor 2 / chemistry
  • Plasminogen Activators / chemistry*
  • Urokinase-Type Plasminogen Activator / chemistry
  • Urokinase-Type Plasminogen Activator / immunology


  • Antibodies, Monoclonal
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Activator Inhibitor 2
  • Plasminogen Activators
  • Fibrinolysin
  • Urokinase-Type Plasminogen Activator