A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase

The secretion of plasminogen activators has been implicated in the controlled extracellular proteolysis that accompanies cell migration and tissue remodeling. We found that the human plasminogen activator urokinase (Uk) (Mr 55,000 form) binds rapidly, specifically, and with high affinity to fresh human blood monocytes and to cells of the monocyte line U937. Upon binding Mr 55,000 Uk was observed to confer high plasminogen activator activity to the cells. Binding of the enzyme did not require a functional catalytic site (located on the B chain of the protein) but did require the noncatalytic A chain of Mr 55,000 Uk, since Mr 33,000 Uk did not bind. These results demonstrate the presence of a membrane receptor for Uk on monocytes and show a hitherto unknown function for the A chain of Uk: binding of secreted enzyme to its receptor results in Uk acting as a membrane protease. This localizes plasminogen activation near the cell surface, an optimal site to facilitate cell migration.

[1]  D. Belin,et al.  Concomitant secretion of prourokinase and of a plasminogen activator- specific inhibitor by cultured human monocytes-macrophages , 1984, The Journal of experimental medicine.

[2]  H. Chapman,et al.  Degradation of fibrin and elastin by intact human alveolar macrophages in vitro. Characterization of a plasminogen activator and its role in matrix degradation. , 1984, The Journal of clinical investigation.

[3]  L. Ossowski,et al.  Antibodies to plasminogen activator inhibit human tumor metastasis , 1983, Cell.

[4]  E. Hoal,et al.  The regulation of tissue plasminogen activator activity by human fibroblasts , 1983, Cell.

[5]  K. Mann,et al.  Functional prothrombinase complex assembly on isolated monocytes and lymphocytes. , 1983, The Journal of biological chemistry.

[6]  R. Bliem,et al.  Production of human plasminogen activators by cell culture , 1983 .

[7]  E. Wilson,et al.  The secretion of plasminogen activators by human myeloid leukemic cells in vitro. , 1983, Blood.

[8]  J. Drapier,et al.  Importance, localization and functional properties of the cell-associated form of plasminogen activator in mouse peritoneal macrophages. , 1983, Biochimica et biophysica acta.

[9]  P. Seeburg,et al.  Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli , 1983, Nature.

[10]  R. Bar-Shavit,et al.  Chemotactic response of monocytes to thrombin , 1983, The Journal of cell biology.

[11]  J. Zeuthen,et al.  Purification of zymogen to plasminogen activator from human glioblastoma cells by affinity chromatography with monoclonal antibody. , 1982, Biochemistry.

[12]  E. Kruithof,et al.  Isolation from human plasma of a plasminogen activator identical to urinary high molecular weight urokinase. , 1982, The Journal of clinical investigation.

[13]  L. Flohé,et al.  The primary structure of high molecular mass urokinase from human urine. The complete amino acid sequence of the A chain. , 1982, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[14]  L. Flohé,et al.  The complete amino acid sequence of low molecular mass urokinase from human urine. , 1982, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[15]  L. Ossowski,et al.  A proenzyme form of human urokinase. , 1982, The Journal of biological chemistry.

[16]  W. Schleuning,et al.  Isolation and characterization of urokinase from human plasma. , 1982, The Journal of biological chemistry.

[17]  H. Chapman,et al.  Macrophage fibrinolytic activity: Identification of two pathways of plasmin formation by intact cells and of a plasminogen activator inhibitor , 1982, Cell.

[18]  L. Flohé,et al.  Structural relationship between human high and low molecular mass urokinase. , 1982, Hoppe-Seyler´s Zeitschrift für physiologische Chemie.

[19]  O. Matsuo,et al.  Comparison of the Relative Fibrinogenolytic, Fibrinolytic and Thrombolytic Properties of Tissue Plasminogen Activator and Urokinase in Vitro , 1981, Thrombosis and Haemostasis.

[20]  R. Simmer,et al.  Protease-nexin: A cellular component that links thrombin and plasminogen activator and mediates their binding to cells , 1980, Cell.

[21]  P. Black,et al.  Evidence for membrane association of plasminogen activator activity in mouse macrophages. , 1980, Biochemical and biophysical research communications.

[22]  G. Markus,et al.  Content and characterization of plasminogen activators in human lung tumors and normal lung tissue. , 1980, Cancer research.

[23]  D. Loskutoff Effects of acidified fetal bovine serum on the fibrinolytic activity and growth of cells in culture , 1978, Journal of cellular physiology.

[24]  A. Granelli‐Piperno,et al.  A study of proteases and protease-inhibitor complexes in biological fluids , 1978, The Journal of experimental medicine.

[25]  J. Vassalli,et al.  Macrophage plasminogen activator: induction by concanavalin A and phorbol myristate acetate , 1977, Cell.

[26]  S. Strickland,et al.  Plasminogen activator in early embryogenesis: Enzyme production by trophoblast and parietal endoderm , 1976, Cell.

[27]  J. Vassalli,et al.  Macrophage plasminogen activator: Modulation of enzyme production by anti-inflammatory steroids, mitotic inhibitors, and cyclic nucleotides , 1976, Cell.

[28]  K. Nilsson,et al.  Establishment and characterization of a human histiocytic lymphoma cell line (U‐937) , 1976, International journal of cancer.

[29]  C. Kahn,et al.  Demonstration that monocytes rather than lymphocytes are the insulin-binding cells in preparations of humah peripheral blood mononuclear leukocytes: implications for studies of insulin-resistant states in man. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Sjöquist,et al.  Protein a from Staphylococcus aureus. Its isolation by affinity chromatography and its use as an immunosorbent for isolation of immunoglobulins , 1972, FEBS letters.

[31]  D. Deutsch,et al.  Plasminogen: Purification from Human Plasma by Affinity Chromatography , 1970, Science.

[32]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[33]  L. Orci,et al.  The insulin receptor of a human monocyte-like cell line: characterization and function. , 1984, Endocrinology.

[34]  B. Ozanne,et al.  Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[35]  E. Reich ACTIVATION OF PLASMINOGEN: A GENERAL MECHANISM FOR PRODUCING LOCALIZED EXTRACELLULAR PROTEOLYSIS , 1978 .

[36]  R. Berlin Molecular basis of biological degradative processes , 1978 .