Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin (Vn): Mapping the binding sites on PAI-1 and Vn

  • Schroeck F
  • Arroyo de Prada N
  • Sperl S
 et al. 
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Abstract

The serpin plasminogen activator inhibitor type-1 (PAI-1), as the primary physiological inhibitor of both urokinase-type (uPA) and tissue-type (tPA) plasminogen activator, plays an important role in the regulation of the fibrinolytic system as well as in extracellular remodeling in both physiological and pathophysiological processes. In plasma as well as in the extracellular matrix PAI-1 binds to vitronectin (Vn), an interaction that affects the function of both proteins. As PAl-1/Vn interaction has a significant regulatory function in fibrinolysis, thrombolysis, and cell adhesion in cancer spread, there is a strong interest in defining the binding sites on PAI-1 and Vn as the basis of a rational design of novel drugs that may modulate PAI-1/Vn-mediated effects. In this minireview, we give an overview on the approaches to define the Vn binding site of PAI-1 and vice versa. Although in the case of PAI-1 the region around alpha-helix E and alpha-helix F of PAI-1 has been demonstrated to be important for its interaction with Vn, the precise location of the Vn-binding region has not completely been resolved. The major high-affinity PAI-1 binding region of Vn is localized within the N-terminal somatomedin B (SMB) domain of Vn. There are indications for at least one other low-affinity PAI-1 binding site in the C-terminal region of Vn, which seems to be involved in the formation of larger PAI-1/Vn complexes.

Author-supplied keywords

  • Cancer
  • Fibrinolysis
  • Plasminogen activator inhibitor type-1
  • Protein-protein interaction
  • Vitronectin

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Authors

  • Florian Schroeck

  • Nuria Arroyo de Prada

  • Stefan Sperl

  • Manfred Schmitt

  • Viktor Magdolen

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