Novel interactions between urokinase and its receptor

Urokinase-type plasminogen activator (uPA) binds to its receptor (uPAR) wit h a K-d of about 1 nM. The catalytic activity of the complex is apparent at uPA concentrations close to K-d. Other functions of the complex, such as s ignal transduction, are apparent at much higher concentrations (35-60 nM). In the present study, we show that uPA and recombinant soluble uPAR (suPAR) , at concentrations that exceed the K-d and the theoretical saturation leve ls (10-80 nM), establish novel interactions that lead to a further increase in the activity of the single-chain uPA (scuPA)/suPAR and two-chain uPA (t cuPA)/suPAR complexes. Experiments performed using dynamic light scattering , gel filtration, and electron microscopy techniques indicate that suPAR fo rms dimers and oligomers, The three techniques provide evidence that the ad dition of an equimolar concentration of scuPA leads to the dissociation of these dimers and oligomers, Biacore data show that suPAR dimers and oligome rs bind scuPA with decreased affinity when compared with monomers, We postu late that uPAR. is present in equilibrium between oligomer/dimer/monomer fo rms. The binding of uPA to suPAR dimers and oligomers occurs with lower aff inity than the binding to monomer. These novel interactions regulate the ac tivity of the resultant complexes and may be involved in uPA/uPAR mediated signal transduction.