RECEPTOR-MEDIATED ENDOCYTOSIS OF PLASMINOGEN ACTIVATORS AND ACTIVATORINHIBITOR COMPLEXES/

Recent findings have elucidated the mechanism for clearance from the e xtracellular space of the two types of plasminogen activators, urokina se-type plasminogen activator (u-PA) and tissue-type plasminogen activ ator (t-PA), and their type-1 inhibitor (PAI-1). Activator/PAI-1 compl exes and uncomplexed t-PA bind to the multiligand receptors alpha(2)-m acroglubulin receptor/low density lipoprotein receptor-related protein (alpha(2)MR) and epithelial glycoprotein 330 (gp330). These receptors mediate endocytosis and degradation of u-PA/PAI-1 complex bound to th e glycosyl phosphatidyl inositol-anchored urokinase receptor (u-PAR) o n cell surfaces, and participate, in cooperation with other receptors, in hepatic clearance of activator/PAI-1 complexes and uncomplexed t-P A from blood plasma. The alpha(2)MR- and gp330-mediated endocytosis of a ligand (u-PA/PAI-1 complex) initially bound to another receptor (u- PAR) is a novel kind of interaction between membrane receptors. Bindin g to alpha(2)MR and gp330 is a novel kind of molecular recognition of serine proteinases and serpins.