Regulation of single chain urokinase by small peptides.
Whether single chain urokinase (scuPA) expresses intrinsic enzymatic activity continues to be a subject of controversy. We report that the activity of scuPA is enhanced by a small plasmin substrate, H-D-valyl-L-leucyl-L-lysine-p-nitroanilide diacetate (D-VLK-p), but not by a second plasmin substrate, H-D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide diacetate (*L*YK-p). D-VLK-p had no effect on the activity of a plasmin insensitive scuPA variant (scuPA-glu158) indicating that native scuPA can be cleaved by plasmin even at saturating concentrations of D-VLK-P. In contrast, D-VLK-P inhibited the activity of the native and scuPA-glu158 complexed with soluble urokinase receptor. Further, D-VLK-p stimulated the enzymatic activity of low molecular weight scuPA (amino acids 144-410) suggesting that D-VLK-P interacts with a second, previously undescribed regulatory site in scuPA.
Higazi A al-R
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia 191904, USA.
Cines
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D002863:Chromogenic Compounds / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D002863:Chromogenic Compounds; C524898:PLAUR protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator