Sequential receptor cascade for coagulation proteins on monocytes. Constitutive biosynthesis and functional prothrombinase activity of a membrane form of factor V/Va. 1989

D C Altieri, and T S Edgington
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.

Cells of monocytic differentiation can promote proteolytic activation of factor X following binding to the adhesive receptor Mac-1. We now show that the product, factor Xa, binds to a second receptor on these cells in a Ca2+-dependent reaction. Functionally, this results in the capacity to convert prothrombin to thrombin. The factor Xa receptor was identified by monoclonal antibody (7G12) reactive with plasma factor V/Va, but selected for reactivity with THP-1 cells. It reacted with 71.2 +/- 10.1% of monocytes, bound 153,600 +/- 33,500 sites/THP-1 cell, blocked binding of 125I-factor Xa, inhibited formation of thrombin, and immunoprecipitated 125I-factor Xa chemically cross-linked to its receptor on THP-1 cells. Following surface iodination or intrinsic labeling of THP-1 cells, antibody 7G12 immunoprecipitated a 74-kDa molecular species, similar to plasma factor Va light chain. Thus, monocytes and monocyte-like cells synthesize and express a factor V/Va-like receptor for factor Xa and organize a functional prothrombinase complex. The simultaneous membrane coexpression of a factor X receptor (Mac-1) and a factor Xa receptor as demonstrated by two-color flow cytofluorometric analysis of monocytes or THP-1 cells is consistent with a sequential receptor cascade for coordinated molecular assembly of coagulation proteins on specialized cells.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010980 Platelet Membrane Glycoproteins Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors. PM-GP,Platelet Glycoprotein,Platelet Membrane Glycoprotein,PM-GPs,Platelet Glycoproteins,Glycoprotein, Platelet,Glycoprotein, Platelet Membrane,Glycoproteins, Platelet,Glycoproteins, Platelet Membrane,Membrane Glycoprotein, Platelet,Membrane Glycoproteins, Platelet,PM GP
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005165 Factor V Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease. Coagulation Factor V,Proaccelerin,AC Globulin,Blood Coagulation Factor V,Factor 5,Factor Five,Factor Pi,Factor V, Coagulation
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000936 Antigen-Antibody Complex The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES. Immune Complex,Antigen-Antibody Complexes,Immune Complexes,Antigen Antibody Complex,Antigen Antibody Complexes,Complex, Antigen-Antibody,Complex, Immune,Complexes, Antigen-Antibody,Complexes, Immune

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