Regulation of urokinase/urokinase receptor interaction by heparin-like glycosaminoglycans

We show here that the interaction between the urokinase-type plasminogen ac tivator and its receptor, which plays a critical role in cell invasion, is regulated by heparan sulfate present on the cell surface and in the extrace llular matrix. Heparan sulfate oligomers showing a composition close to the dimeric repeats of heparin (glucosamine-NSO3(6-OSO3)-iduronic acid (2-OSO3 )) n = 5 and n > 5, where iduronic acid may alternate with glucuronic acid, exhibit affinity for urokinase plasminogen activator and confer specificit y on urokinase/urokinase receptor interaction. Cell surface clearance of he paran sulfate reduces the affinity of such interaction with a parallel decr ease of specific urokinase binding in the presence of an unaltered expressi on of receptor. Transfection of human urokinase plasminogen activator recep tor in normal Chinese hamster ovary fibroblasts and in Chinese hamster ovar y cells defective for the synthesis of sulfated glycosaminoglycans results in specific urokinase/receptor interaction only in nondefective cells. Hepa ran sulfate/urokinase and receptor/urokinase interactions exhibit similar K -d values. We concluded that heparan sulfate functions as an adaptor molecu le that confers specificity on urokinase/receptor binding.