Identification of a protease inhibitor produced by astrocytes that is structurally and functionally homologous to human protease nexin-I.
In the present studies we have compared the structural and biochemical properties of human protease nexin-I (PN-I) and a protease inhibitor present in the serum-free culture fluid of normal rat brain astrocytes. The inhibitor binds to and forms covalent complexes with human urokinase and thrombin. The inhibitor has an approximate Mr = 43,000 based on the size of the complexes (deduced from SDS-PAGE) and mediates the cellular binding and uptake of the proteases to which it links. Binding is heparin sensitive and occurs on a cell surface receptor that also binds complexes formed between proteases and a well-characterized cell-secreted protease inhibitor, human PN-I. In addition, the inhibitor co-migrates with PN-I on SDS-PAGE and cross-reacts with anti-PN-I antibody on immunoblots. A similar molecule, designated NPF, is produced by C6 glioma cells in culture and has neurite promoting activity on a neuroblastoma cell line.
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D003429:Cross Reactions; D003470:Culture Media; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007158:Immunologic Techniques; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D058255:Protease Nexins; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D003470:Culture Media; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator