Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpesviral infection of endothelial cells (ECs) induces arterial injury. We now demonstrate that such infection promoted enhanced monocyte-endothelial adhesion. Enhanced adhesion was blocked by monoclonal antibodies to the viral-encoded cell surface glycoprotein gC but not by antibodies to gD or gE. Adhesion was also blocked by treating ECs with specific thrombin inhibitors or by growing cells in prothrombin-depleted serum. We found that gC bound and promoted activation of factor X on infected ECs, thereby contributing to thrombin generation. Factor X also bound to transfected L cells that were induced to express gC. Cross-linking and immunoprecipitation studies demonstrated factor X-gC complex formation on the surface of these cells. We suggest that gC-dependent thrombin generation by herpes-infected endothelium may be an important mediator of vascular pathology during viral infection.
...
PMID:Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells. 216 Aug 55

Focal adhesion of leukocytes to the blood vessel lining is a key step in inflammation and certain vascular disease processes. Endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell surface glycoprotein expressed by cytokine-activated endothelium, mediates the adhesion of blood neutrophils. A full-length complementary DNA (cDNA) for ELAM-1 has now been isolated by transient expression in COS cells. Cells transfected with the ELAM-1 clone express a surface structure recognized by two ELAM-1 specific monoclonal antibodies (H4/18 and H18/7) and support the adhesion of isolated human neutrophils and the promyelocytic cell line HL-60. Expression of ELAM-1 transcripts in cultured human endothelial cells is induced by cytokines, reaching a maximum at 2 to 4 hours and decaying by 24 hours; cell surface expression of ELAM-1 protein parallels that of the mRNA. The primary sequence of ELAM-1 predicts an amino-terminal lectin-like domain, an EGF domain, and six tandem repetitive motifs (about 60 amino acids each) related to those found in complement regulatory proteins. A similar domain structure is also found in the MEL-14 lymphocyte cell surface homing receptor, and in granule-membrane protein 140, a membrane glycoprotein of platelet and endothelial secretory granules that can be rapidly mobilized (less than 5 minutes) to the cell surface by thrombin and other stimuli. Thus, ELAM-1 may be a member of a nascent gene family of cell surface molecules involved in the regulation of inflammatory and immunological events at the interface of vessel wall and blood.
...
PMID:Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. 246 35

When platelets bind certain specific ligands they are induced to secrete the contents of their cytoplasmic granules and to aggregate. Studies of the molecular events accompanying this vital physiological response have led to a greater understanding of cell activation in general since the pathways involved are common to a number of cell types. By contrast most of the information about the cell surface molecules that initiate signal transduction has emerged from work on T lymphocyte activation, a process essential to the initiation of the immune response. We have described an activation antigen on T lymphocytes that is involved in the differentiation of these cells. In the present report it is demonstrated that the antigen is expressed on the platelet membrane with about 1,200 copies/platelet. A monoclonal antibody detecting this antigen stimulates platelet secretion and aggregation with a half-maximal response at approximately 10(-8) M. Characterization of the antigen, termed PTA1, reveals a glycoprotein of Mr 67,000 showing extensive N-linked carbohydrate, much of which appears to be heavily sialated. The amino-terminal sequence of PTA1, EEVLWHTSVPFAEXMSLEXVYPSM, indicates that the protein has not previously been characterized. Preliminary investigation of the mechanism by which PTA1 mediates platelet activation suggests involvement of protein kinase C and the 47-kDa protein of platelets is rapidly phosphorylated upon antibody-mediated activation. During this process PTA1 is also phosphorylated, as it is following platelet activation by the other agonists, collagen, thrombin, and 12-O-tetradecanoylphorbol 13-acetate. These results provide the first example of a cell surface glycoprotein that is directly involved in both platelet and T lymphocyte activation.
...
PMID:Characterization of a novel membrane glycoprotein involved in platelet activation. 276 31

A 140 000 D glycoprotein (140 kD gp), labelled radioactively with surface-specific techniques, remained as the major cell surface glycoprotein in the detergent-resistant cytoskeletal preparations of cultured human fibroblasts. The 140 kD gp was present also in trypsinized cells and was not affected by treatment of the cells either with collagenase, chymotrypsin or thrombin. In density gradient fractionation of whole cells the 140 kD gp was recovered in the plasma membrane fraction together with small amounts of cytoskeletal components. In fractionation of cytoskeletal preparations, on the other hand, the 140 kD gp could not be dissociated from cytoskeletal proteins and together with vimentin it formed the major component of the oligomeric polypeptide complex generated by treating the surface-labelled cytoskeletal preparations with bifunctional cross-linking reagent, dithiobis succinimidyl propionate (DTPS). Moreover, the 140 kD gp seemed to copurify with vimentin upon reconstitution of intermediate filaments from urea-solubilized cytoskeletal preparations. On the other hand, low ionic-induced degradation of vimentin led to a decrease in the amount of the detergent-resistant 140 kD gp on the cell surface. In electron microscopy, a close apposition between bilayer-like plasma membrane remnants of the adherent cytoskeletons and cytoskeletal elements could be seen. The results indicate that the 140 kD gp is a plasma membrane glycoprotein which closely interacts with the detergent-resistant cytoskeleton of cultured human fibroblast. Possible mechanisms of the association are discussed.
...
PMID:140 000 Dalton surface glycoprotein. A plasma membrane component of the detergent-resistant cytoskeletal preparations of cultured human fibroblasts. 633 55

This study was based on our previous findings that the mitogenic action of thrombin on cultured fibroblasts can result from interaction of thrombin with the cell surface in the absence of internalization, and that the proteolytic activity of thrombin is required for stimulation of cell division. This prompted us to look for thrombin-mediated cleavages using 2-dimensional gel electrophoresis of labeled cell surface proteins. Surface membrane components were labeled by 3 procedures: 1) proteins were labeled by lactoperoxidase-catalyzed iodination using 125I-; 2) galactose and galactosamine residues of glycoproteins were oxidized with galactose oxidase and reduced with 3H-NaBH4; and 3) glycoproteins were metabolically labeled by incubating cells with 3H-fucose. labeling with the first 2 procedures was carried out after thrombin treatment; in contrast, cells metabolically labeled with 3H-fucose were subsequently treated with thrombin to look for proteolytic cleavages. Collectively, these studies indicated that only about 5 cell surface proteins were thrombin-sensitive, consistent with the high specificity of this protease. Each of the labeling procedures revealed a thrombin-sensitive cell surface glycoprotein which was identified as fibronectin by immunoprecipitation experiments. In addition, cell surface proteins of about 140K and 55K daltons were thrombin-sensitive. However, cell surface proteins of about 45K daltons and 130K to 150K daltons were increased after thrombin treatment. These experiments were conducted on an established line of Chinese hamster lung cells with the eventual goal of studying thrombin-mediated cleavages of cell surface proteins in a large number or in cloned populations derived from this line that are either responsive or unresponsive to the mitogenic action of thrombin. This approach should permit identification of proteolytic cleavages tha are necessary for thrombin-stimulated cell division.
...
PMID:Cleavage of cell surface proteins by thrombin. 725 49

Thrombomodulin is an endothelial cell surface glycoprotein that forms a 1:1 complex with thrombin. In this form, thrombin can activate approximately 1,000-fold more protein C than thrombin alone and does not activate coagulation factors, V and VIII, and platelets. Activated protein C inactivates factors Va and VIIIa. Thus thrombomodulin converts thrombin from a procoagulant protease to an anticoagulant. The soluble thrombomodulin present in human urine and plasma appears to represent a truncated form that lacks the transmembrane and cytoplasmic domains of tissue thrombomodulin. The plasma level of thrombomodulin has been used as a marker for endothelial injury in vivo. Elevated levels of soluble thrombomodulin were reported in the plasma from the patients with disseminated intravascular coagulation, adult respiratory distress syndrome (ARDS), and diabetes mellitus retinopathy.
...
PMID:[Soluble thrombomodulin: as a marker of endothelial injury]. 805 97

Thrombomodulin is an endothelial cell surface glycoprotein that inhibits the procoagulant activities of thrombin and accelerates activation of the anticoagulant protein C. Because protein C deficiency is associated with cutaneous thrombosis, we investigated the expression of thrombomodulin in human skin. Thrombomodulin was detected by immunohistochemical staining both in dermal endothelial cells and in epidermal keratinocytes. Within the epidermis, thrombomodulin staining was limited to keratinocytes of the spinous layer, suggesting that thrombomodulin is induced when basal keratinocytes begin to terminally differentiate. Thrombomodulin expression also correlated with squamous differentiation in epidermal malignancies; little or no thrombomodulin staining was seen in five basal cell carcinomas, whereas strong thrombomodulin staining was observed in each of five squamous cell carcinomas. Human foreskin keratinocytes cultured in medium containing 0.07 mM calcium chloride synthesized functional thrombomodulin with cofactor activity comparable to thrombomodulin in human umbilical vein endothelial cells. Stimulation of keratinocyte differentiation with 1.4 mM calcium chloride for 48 h produced 3.5-, 3.2-, and 5.6-fold increases in thrombomodulin cofactor activity, antigen, and mRNA, respectively. These observations suggest that thrombin is regulated by keratinocyte thrombomodulin at sites of cutaneous injury, and indicate a potential role for thrombomodulin in epidermal differentiation.
...
PMID:Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation. 816 84

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.
...
PMID:Endothelial cell activation in cutaneous vasculitis. 868 65

Thrombomodulin (TM) is an endothelial cell surface glycoprotein which converts thrombin from a procoagulant protease to an anticoagulant. We have previously reported that TM is a useful marker for immunohistochemical diagnosis of angiogenic tumors and also have reported that TM is expressed on squamous cell carcinoma (SCC) of the human esophagus. In addition, the expression of TM is significantly decreased in metastatic foci in lymph nodes compared with that in primary lesions. In order to reveal the biological significance of TM in SCC, we subcloned and established two different cell lines, i.e. TM-high-expressing (TE3HTM) cells and TM-low-expressing (TE3LTM) cells, from a human SCC cell line, TE3, using fluorescence-activated cell sorter (FACS) and examined the biological characteristics of these variant cell lines. These tumor cells revealed very similar morphological figures in ordinary cultured conditions and showed almost equal growth rates under various cultured conditions. By the invasion assay of these tumor cells using matrigel, we found that TE3LTM cells showed significantly increased invasive ability compared with that of TE3HTM cells. Characteristic intercellular localization of TM and a different manner of invasiveness between TE3LTM cells and TE3HTM cells suggest that TM may act as a cell-to-cell interaction molecule.
...
PMID:A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin-expressing clone--thrombomodulin as a possible candidate for an adhesion molecule of squamous cell carcinoma. 961 77

The tissue factor (TF) coagulation pathway is initiated when circulating factor (F)VII(a) encounters TF, a cell surface glycoprotein, as a result of vascular injury or pathological perturbation. TF-induced coagulation plays a primary role in hemostasis and also in the pathogenesis of various thrombotic disorders. Recent studies suggest that activation of the TF-pathway may also contribute to other pathophysiological processes by altering intracellular responses, either directly or via activated factor X (FXa) and thrombin generation. Therefore, suppression of the aberrant expression of TF/FVIIa on cell surfaces not only prevents thrombotic disorders but may also provide other protective effects. Recent ex-vivo and in-vivo experiments document the effectiveness of active site-blocked activated factor VII (FVIIai) in inhibiting TF-mediated injury. It is generally believed that FVIIai exerts its effects by limiting the formation of functional TF/FVIIa complexes by directly competing with plasma FVII(a) for limited available TF sites on cell surfaces. Although such competition can explain the effectiveness of FVIIai immediately after administration, it is not clear how it exerts its prolonged effects. In this manuscript, we summarize the use of FVIIai as an antithrombotic agent in various model systems and discuss potential mechanisms by which FVIIai may exert protective effects.
...
PMID:Active site-blocked activated factor VII as an effective antithrombotic agent: mechanism of action. 1085 May 80


1 2 Next >>

---