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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five rat thyroid cell lines were tested for the expression of the cell surface receptor for urokinase type plasminogen activator (uPA). All tested lines were found to bind uPA, but transformed 1-5G and Ki-Mol cells, which are also high uPA producers, bound at least ten times more uPA, as compared to non-producers, 'normal' TL5 cells. Moreover, it was possible to remove membrane-bound uPA by treating the cells with phosphatidylinositol-specific phospholipase C, suggesting that rat uPAR, like its human counterpart, is linked to the membrane by a glucosyl-phosphatidylinositol anchor. The specificity of the binding was tested by competition with three different synthetic peptides corresponding to amino acids 14-37 of human, rat and mouse uPA. The results indicate also that the receptor binding region of rat uPA is located within the growth factor domain of the molecule and that its expression may be dependent on the transformed state of the cells.
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PMID:The receptor for the plasminogen activator of urokinase type is up-regulated in transformed rat thyroid cells. 132 34

The Epstein-Barr virus (EBV)-encoded membrane protein, LMP, is expressed in a proportion of undifferentiated nasopharyngeal carcinomas (NPC). Previous studies have shown that the transfection of the gene encoding LMP into a human keratinocyte line, RHEK-1, induces morphological alterations and a reduced expression of cytokeratins. We have analyzed immunophenotypic changes in the RHEK-1 line following LMP-transfection and compared these changes with the phenotype of NPC biopsies. We demonstrate a downregulation of two epithelial markers, an epithelial glycoprotein (EGP) defined by the monoclonal antibody Ber-EP4 and the epithelial membrane antigen (EMA). Furthermore, a lymphocyte activation-associated antigen, CDw70 antigen, which was absent from the parental line was expressed in virtually all LMP-transfected cells, whereas no similar effect was seen with respect to the CD30 activation antigen. Nine EBV-positive human NPCs, six of which were LMP-positive expressed the EGP and EMA. The CDw70 antigen, which is not normally present in epithelial cells, was expressed in eight biopsies, whereas the CD30 antigen was not detectable. Our findings are in keeping with the notion that LMP expression may contribute to the immunophenotype of human NPCs.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:The Epstein-Barr virus encoded membrane protein (LMP) induces phenotypic changes in epithelial cells. 135 76

The biochemical structure of CD69 early activation antigen has been characterized by means of two newly isolated mAb, namely C1.18 and E16.5. Upon analysis by SDS-PAGE, C1.18-reactive molecules immunoprecipitated from 125I-surface labeled PMA activated PBL consisted of a 32 + 32 kD dimer, a 32 + 26 kD dimer, a 26 + 26 kD dimer and a 21 + 21 kD dimer. E16.5-reactive molecules consisted of a 26 + 26 kD dimer and a 21 + 21 kD dimer. Cross absorption experiments showed that E16.5 mAb reacts with an epitope of the CD69 molecule distinct from the one recognized by C1.18 mAb and present only on a subpopulation of the CD69 molecular pool. The patterns of migration of C1.18- and E16.5-reactive molecules in two-dimensional gel-electrophoresis, under reducing conditions before and after treatment with Endoglycosidase F enzyme suggest that the two mAb recognize the same glycoprotein structure, but in two distinct glycosylation forms, both expressed on the cell surface membrane. Finally, p32, p26 and p21 of CD69 complex obtained from three distinct normal donors did not show appreciable structural polymorphism, by two-dimensional peptide mapping, not only among single subunits within the same individual, but also among homologous subunits in distinct individuals. Further, it was found that CD69 complex is expressed at the cell surface of resting PBL, although at a very reduced level in comparison to PMA activated cells. C1.18 and E16.5 mAb induced comparable cell proliferation and IL-2 production in PBL in the presence of PMA. C1.18 mAb increased intracellular free calcium concn in PMA activated PBL after cross-linking with goat anti mouse Ig, while the effect induced by E16.5 mAb after cross-linking was consistently lower. Finally, it was found that Sepharose-linked C1.18 mAb, in the presence of rIL-2 or PMA, did not induce TNF release from 6 NK cell clones.
Mol Immunol
PMID:Structural analysis of the CD69 early activation antigen by two monoclonal antibodies directed to different epitopes. 170 36

Mononuclear phagocytes and dendritic cells are potent antigen-presenting cells that localize to distinct microenvironmental compartments in many different organs. These cells are particularly plentiful in spleen and lymph node. Recently, these cells have been identified and immunophenotypically characterized in human tissue sections using monoclonal antibodies. However, similar studies in animal species, particularly those representing models of human diseases, have yet to be completely performed. We have evaluated 18 monoclonal reagents raised against human determinants for their reactivity with macrophages and dendritic cells in lymphoid organs of rhesus monkeys. Six of the 18 (EBM11, 25F9, Mol, R4/23, To5, and SK9) produced labeling patterns in rhesus monkey lymphoid tissue that paralleled the staining patterns described for human tissues. Seven others (KB90, FMC17, Mo3, PHM3, PHM2, G16/1, and 27E10) stained varying subsets of specific cells types in these simian tissues. These reagents are requisite for the future study in an experimental animal of the afferent immune response in both normal and disease states.
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PMID:Immunophenotypic characterization of mononuclear phagocytes and dendritic cells in lymphoid organs of the rhesus monkey. 246 Dec 68

Mo1, 2, 3, and 4, and Plt-1 are a series of five distinct antigens detected on the surface of human peripheral blood monocytes by mouse monoclonal antibodies. Mo2 and 3 are restricted to the monocyte-macrophage series, while Mo1, as previously reported, is also expressed by human granulocytes and null cells. Mo3, as distinguished from Mo1 and Mo2, is weakly expressed by virgin peripheral blood monocytes but becomes well expressed if monocytes are cultured overnight at 37 degrees C. Mo4 is coexpressed by monocytes and platelets, while Plt-1 appears to be a platelet-specific antigen whose detection on monocytes reflects adherence of platelets to monocyte membranes. That Mo2-4 are true monocyte antigens is demonstrated by their resynthesis following protease treatment of monocytes (Mol expression is resistant to proteolytic digestion). During myeloid-monocyte differentiation, the Mo antigens are infrequently expressed by immature myeloid cells but are found at higher frequency on leukemic monocytic forms. Macrophages from cultured peripheral blood monocytes and HL-60 cells exposed to lymphokines or phorbol diester express Mo1-4, but noncirculating peritoneal macrophages lack Mo3. The Mo antigens are differentiation markers whose expression reflects membrane heterogeneity during myeloid-monocyte-macrophage maturation.
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PMID:Analysis of antigenic determinants on human monocytes and macrophages. 617 62

Macrophages have been obtained from the peritoneal cavities of C57BL/6 mice following treatment with C. parvum, MVE-2, mineral oil, or thioglycollate. Cell populations were primarily composed of mononuclear phagocytes as determined by a latex bead uptake assay. Macrophages obtained from C. parvum or MVE-2 were activated as judged by enhanced cytostatic activity against two tumor cell target lines. Thioglycollate-elicited macrophages demonstrated much lower cytostatic ability. Rats were immunized with activated MVE-2 macrophages. Hybridomas were prepared by fusion with a non-secreting myeloma cell line followed by cloning. Cell supernates were selected on the basis of binding to activated but not elicited macrophages. The monoclonal antibody produced has been characterized by flow cytometry. The antibody does not react with syngeneic erythrocytes, thymocytes, or spleen cells. Reaction with thioglycollate macrophages is very low. Alternatively, intense binding is found on activated macrophages. This antigen which accompanies macrophage activation for tumor cell cytostasis is designated as macrophage activation antigen-1 (MAA-1). Several important physiological changes accompany the process of macrophage activation. For example, activated macrophages demonstrate enhanced microbicidal, phagocytic, secretory, and tumoricidal activity (for reviews see refs. 1,2). Concommitant alterations in cell surface properties have been observed. These include: (a) changes in surface morphology and spreading (3-5), (b) altered lipid and protein content (6,7), (c) decreases in 5'-nucleotidase activity and alkaline phosphodiesterase (8), increases in leucine aminopeptidase (8), decreases in mannose receptors (11,12), and antigen F4/80 (11), (d) increases in Ia antigens (11,12), and (e) increased tumor cell binding (13). These structural and functional modifications indicate that activated macrophages represent a unique class of functionally differentiated cells (9). Antigenic modifications accompanying macrophage differentiation are of special interest. Markers for specific macrophage classes might be useful in defining differentiation pathways, dissecting type-specific functional activities such as tumor cytotoxicity, and providing a means to identify macrophage subsets in heterogeneous cell populations. In the present work we have taken the first step in this direction by defining a cell surface macrophage activation antigen.
Mol Immunol 1984 Jul
PMID:Characterization of a monoclonal antibody defining a macrophage activation-specific cell surface antigen. 674 39

CD30L, the ligand for the activation antigen CD30, is a member of the tumor necrosis factor family of cytokines. Binding of CD30L to CD30, which is a member of the nerve growth factor/tumor necrosis factor receptor family, induces proliferation in peripheral blood lymphocytes and Hodgkin's derived cell lines with a T-cell phenotype such as HDLM-2 and L540, while cell lines derived from anaplastic large cell lymphomas, such as Karpas 299, undergo cell death. In order to investigate whether mutations of the CD30 antigen are responsible for these opposite effects, we cloned the open reading frame of CD30 cDNAs from the cell lines L540 and Karpas 299 and from peripheral blood lymphocytes by reverse transcriptase polymerase chain reaction. Sequencing of independent plasmid clones revealed that these cells have a silent transition (A-->G) at position 771 of the open reading frame compared to the published sequence derived from the HTLV-1+ cell line HUT-102. As published data have shown that crosslinking of CD30 induces an elevation of cytosolic free calcium ([Ca2+]i) in TCR positive Jurkat cells, we have analysed the effect of crosslinking of CD30 on L540 and Karpas 299 cells. No elevations of [Ca2+]i have been observed in these cell lines after crosslinking of CD30 with HRS-4. We conclude (i) that the different functional effects of CD30 in PBL, L540 and Karpas 299 are not due to differences in the primary structure of the receptor; and (ii) that the different responses observed upon engagement with CD30L for the cell lines L540 and Karpas 299 do not correlate with differences in mobilization of [Ca2+]i after crosslinking of CD30.
Mol Immunol 1994 Dec
PMID:Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources. 752 1

Complex between urokinase and its type-1 inhibitor (uPA-PAI-1) may, when bound to the urokinase receptor (uPAR), be endocytosed by an ensuing binding of the complex to the multiligand receptors alpha (2)-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) and glycoprotein 330 (gp330). We have found that phorbol esters regulate endocytosis of uPA-PAI-1 differently in different cell lines. In COS-1 cells, expressing uPAR and high levels of alpha 2MR/LRP under basal conditions, phorbol esters cause a time-dependent decrease in endocytosis concomitantly with a parallel down-regulation of alpha 2MR/LRP expression. An up-regulation of uPAR expression was also observed. General endocytosis via the clathrin-coated pit pathway was not affected by PMA treatment, as judged from measurements of transferrin endocytosis. In LLC-PK1 cells, expressing alpha 2MR/LRP but not uPAR under basal conditions, phorbol esters transiently increase endocytosis in parallel with a transient induction of uPAR expression, while there was virtually no change in alpha 2MR/LRP expression. Differential regulation of endocytosis therefore seems to be caused by differential regulation of the receptors, with either the alpha 2MR/LRP-level (in COS)-1 cells) or the uPAR-level (in LLC-PK1 cells) being rate-limiting.
Mol Cell Endocrinol 1995 Apr 01
PMID:Differential regulation of urokinase-type-1 inhibitor complex endocytosis by phorbol esters in different cell lines is associated with differential regulation of alpha 2-macroglobulin receptor and urokinase receptor expression. 766 84

RT6 is a glycosyl phosphatidylinositol-anchored cell membrane protein, whose expression is restricted to peripheral T cells and intraepithelial lymphocytes. It has attracted interest as a T cell differentiation marker and activation antigen in rats. The only known protein to which RT6 shows significant homology is a recently cloned mono(ADP-ribosyl)transferase of rabbit skeletal muscle which is distantly related also to certain bacterial toxins. Intriguingly, whereas the rat carries a single copy RT6 gene with two known highly divergent alleles, the mouse carries two closely linked, functional RT6 genes that show approximately 85% sequence identity. We have now cloned and sequenced the homologues of the RT6 genes from humans of distinct ethnic backgrounds and of the chimpanzee. Surprisingly, in each case, three premature in-frame stop codons preclude expression of the single copy RT6 gene as a cell surface protein. Otherwise, the RT6 genes of human and chimpanzee exhibit high structural conservation to their rodent counterparts. RNA expression analyses indicate that the RT6 gene is not transcriptionally active in human T cells or any other human tissue analyzed so far. To our knowledge, RT6 represents the first mammalian membrane protein identified that has been lost universally in the human and chimpanzee species due to gene inactivation.
J Mol Biol 1994 Oct 28
PMID:Premature stop codons inactivate the RT6 genes of the human and chimpanzee species. 796 80

Binding of urokinase-type plasminogen activator (uPA) to a specific receptor (uPAR) on human lung fibroblasts enables it to regulate cellular proteolysis and remodeling of the extracellular matrix. Binding studies with radiolabeled uPA indicated that both normal and fibrotic lung fibroblasts express the receptor, but cells from fibrotic tissues bound significantly more uPA (P < 0.001). Phorbol myristate acetate, lipopolysaccharide, transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) increased uPA binding and plasminogen activation at the cell surface, with a greater maximal effect on fibrotic than on normal fibroblasts. Excess unlabeled uPA, specific antibody, or antisense oligonucleotides inhibited uPA binding. Ribonuclease (RNase) protection assays showed higher levels of uPAR messenger ribonuleic acid (mRNA) in each of the five fibrotic cell lines than in normal fibroblasts. uPA was mitogenic for normal as well as fibrotic fibroblasts, indicating that receptor binding concurrently localizes cellular proteolytic activity and stimulates mitogenesis. Morphometry and immunohistochemical analysis showed that uPAR, as well as uPA, was increased in fibroblasts in fibrotic lung tissue. Increased expression of uPAR by fibrotic lung fibroblasts and enhanced urokinase binding induced by proinflammatory cytokines suggest a novel mechanism by which fibroblast-mediated matrix remodeling and proliferation may be regulated in interstitial lung diseases.
Am J Respir Cell Mol Biol 1996 Jul
PMID:Differential expression of the urokinase receptor in fibroblasts from normal and fibrotic human lungs. 867 25


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