Receptor-mediated endocytosis of plasminogen activators and activator/inhibitor complexes.
Recent findings have elucidated the mechanism for clearance from the extracellular space of the two types of plasminogen activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA), and their type-1 inhibitor (PAI-1). Activator/PAI-1 complexes and uncomplexed t-PA bind to the multi-ligand receptors alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR) and epithelial glycoprotein 330 (gp330). These receptors mediate endocytosis and degradation of u-PA/PAI-1 complex bound to the glycosyl phosphatidyl inositol-anchored urokinase receptor (u-PAR) on cell surfaces, and participate, in cooperation with other receptors, in hepatic clearance of activator/PAI-1 complexes and uncomplexed t-PA from blood plasma. The alpha 2MR- 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. Binding to alpha 2MR and gp330 is a novel kind of molecular recognition of serine proteinases and serpins.
Andreasen
P A
PA
Department of Molecular Biology, University of Aarhus, Denmark.
Sottrup-Jensen
L
L
Kjøller
L
L
Nykjaer
A
A
Moestrup
S K
SK
Petersen
C M
CM
Gliemann
J
J
D000595:Amino Acid Sequence; D000818:Animals; D004705:Endocytosis; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*
D026541:Heymann Nephritis Antigenic Complex; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D015849:Plasminogen Inactivators; D011971:Receptors, Immunologic; D010960:Plasminogen Activators