Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tethering of plasminogen to cell surfaces controls plasmin formation and, thereby, influences pericellular proteolysis and cell migration. Modulation of cellular plasminogen binding sites provides a mechanism for regulation of these events. In this study, two distinct models, phorbol ester-stimulated adhesion of U937 monocytoid cells and culturing of peripheral blood neutrophils, treatments which modulate plasminogen binding sites, have been examined to determine the molecular basis for the upregulation of plasminogen receptors. Membranes were isolated from cell populations, with and without upregulated plasminogen binding capacities, and analyzed by [(125)I]plasminogen ligand blotting of gel transfers. Approximately 15 different [(125)I]plasminogen-binding proteins were discerned in the membrane fractions, and only relatively minor differences in the intensities of individual bands were noted in the different cell populations. The notable exception was the presence of a 17 kDa band, which was selectively and markedly enhanced in the membranes from cells with enhanced plasminogen binding capacities. The 17 kDa protein was isolated from both cell types, and amino acid sequencing of peptide fragments identified the same protein, histone H2B. Increased expression of histone H2B was observed on stimulated U937 cells and cultured neutrophils by confocal microscopy with an antibody raised to the carboxy-terminal octopeptide sequence of histone H2B. This antibody or its Fab fragments substantially decreased the level of binding of plasminogen to these cultured neutrophils and stimulated U937 cells that exhibited elevated levels of binding but not to nonstimulated cells. Thus, histone H2B represents a regulated plasminogen receptor, which contributes significantly to the plasminogen binding capacity of cells.
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PMID:Identification of histone H2B as a regulated plasminogen receptor. 1687 81

Plasminogen (Plg) facilitates inflammatory cell recruitment, a function that depends upon its binding to Plg receptors (Plg-Rs). However, the Plg-Rs that are critical for cell migration are not well defined. Three previously characterized Plg-Rs (alpha-enolase, annexin 2, and p11) and a recently identified Plg-R (histone H2B [H2B]) were assessed for their contribution to Plg binding and function on macrophages. Two murine macrophage cell lines (RAW 264.7 and J774A.1) and mouse peritoneal macrophages induced by thioglycollate were analyzed. All 4 Plg-Rs were present on the surface of these cells and showed enhanced expression on the thioglycollate-induced macrophages compared with peripheral blood monocytes. Using blocking Fab fragments to each Plg-R, H2B supported approximately 50% of the Plg binding capacity, whereas the other Plg-Rs contributed less than 25%. Anti-H2B Fab also demonstrated a major role of this Plg-R in plasmin generation and matrix invasion. When mice were treated intravenously with anti-H2B Fab, peritoneal macrophage recruitment in response to thioglycollate was reduced by approximately 45% at 24, 48, and 72 hours, with no effect on blood monocyte levels. Taken together, these data suggest that multiple Plg-Rs do contribute to Plg binding to macrophages, and among these, H2B plays a very prominent and functionally important role.
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PMID:Histone H2B as a functionally important plasminogen receptor on macrophages. 1769 Feb 54

Plasminogen is the proenzyme of plasmin, the key protease of the fibrinolytic system, but its role is not limited to fibrinolysis regulation. Plasminogen binds not only to fibrin, but also to different receptors on cell surfaces, including the heterotetrameric complex Annexin A2-S100A10, enolase-1, histone H2B and the plasminogen receptor Plg-R(KT) . These receptors localize plasmin generation to the cell surface and provide a broad spectrum of reactions including proteolytic activity, cell migration and recruitment as well as signaling pathway activation. These plasminogen-binding proteins are involved in both physiologic and pathologic processes such as inflammation, thrombosis and cancer. Thus, plasminogen is at the center of a complex tightly controlled and regulated system where plasminogen-binding proteins have a crucial role, suggesting new therapeutic and diagnostic strategies. This review will discuss currently available information on plasminogen receptors, particularly their mechanisms of action and their roles in inflammatory, autoimmune and malignant disease.
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PMID:Plasminogen receptors and their role in the pathogenesis of inflammatory, autoimmune and malignant disease. 2314 Jan 88