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Related Experiment Videos

Cellular mechanisms regulating non-haemostatic plasmin generation.

R Bass1, V Ellis

  • 1School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, U.K.

Biochemical Society Transactions
|May 25, 2002
PubMed
Summary

Proteases degrade the extracellular matrix, impacting cell behavior and disease. The plasminogen activation system, regulated by cellular receptors, plays a key role in pericellular proteolysis and various pathologies.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathology

Background:

  • Proteases degrade the extracellular matrix (ECM), influencing cell migration, ECM interactions, and growth factor release.
  • The plasminogen activation system is crucial for pericellular proteolysis, implicated in cancer, vascular disorders, and neurodegeneration.

Purpose of the Study:

  • To explore the regulatory mechanisms of plasmin generation via cellular receptors.
  • To understand the role of the plasminogen activation system in various pathological conditions.
  • To investigate the potential involvement of this system in transmissible spongiform encephalopathies.

Main Methods:

  • Focus on the binding of plasminogen activators (urokinase-type and tissue plasminogen activator) to specific cellular receptors (uPAR and a type-II transmembrane protein).

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  • Analysis of the formation of higher-order activation complexes involving membrane-associated plasminogen.
  • Examination of interactions with other cell adhesion and migration proteins.

    • Main Results:

    • Cellular receptors significantly enhance plasminogen activation by forming binary complexes with plasminogen activators.
    • These complexes reduce the K(m) for plasminogen activation and can protect proteases from inhibitors.
    • Interactions with other proteins modulate the proteolytic system's activity.
    • Prion protein forms were observed to stimulate tissue plasminogen activator-mediated plasminogen activation.

    Conclusions:

    • Cellular receptors are central regulators of plasmin generation, controlling pericellular proteolysis.
    • The plasminogen activation system's dysregulation is linked to significant pathologies.
    • The interaction with prion proteins suggests a potential role in transmissible spongiform encephalopathies pathogenesis.