N-Glycans of ADAMTS13 modulate its secretion and von Willebrand factor cleaving activity.


:Severe deficiency of ADAMTS13, a plasma metalloprotease, leads to thrombotic thrombocytopenic purpura. ADAMTS13 contains 10 putative N-glycosylation sites in or near its metalloprotease sequence, spacer region, thrombospondin type 1 repeat no. 4 (TSR no. 4), and CUB domains. Tunicamycin treatment markedly decreased the secretion of ADAMTS13 into the culture medium of transfected cells. Nevertheless, the protease was efficiently secreted from N-acetylglucosaminyltransferase I-deficient Lec1 Chinese hamster ovary cells, indicating that N-glycosylation in the endoplasmic reticulum, but not the conversion of oligomannose to complex N-glycans in the Golgi complex, is important for secretion. However, ADAMTS13 with oligomannose N-glycans cleaved its substrate, von Willebrand factor (VWF) multimers, less effectively, with a higher K(m) but similar k(cat) value. In mutagenesis analysis, decreased secretion and VWF cleaving activity was observed with the N146Q and N828Q mutants, while decreased secretion only was observed with the N552Q mutant of ADAMTS13. Enzymatic removal of N-glycans from ADAMTS13 did not affect its VWF cleaving activity. Thus, N-glycosylation is necessary for efficient secretion of ADAMTS13, while conversion of the N-glycans from oligomannose to complex type in the Golgi complex enhances the proteolytic activity of the protease toward VWF multimers. After its secretion, ADAMTS13 does not require N-glycans for its VWF cleaving activity.






Zhou W,Tsai HM




Has Abstract


2009-01-22 00:00:00
















  • Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia.

    abstract::Mutations in the nucleophosmin 1 (NPM1) gene are considered a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1-mutated (NPM1mut) AML, we applied high-resolution, genome-wide, single-nucleotide polymorphism array profiling to detect copy number ...


    pub_type: 杂志文章


    authors: Krönke J,Bullinger L,Teleanu V,Tschürtz F,Gaidzik VI,Kühn MW,Rücker FG,Holzmann K,Paschka P,Kapp-Schwörer S,Späth D,Kindler T,Schittenhelm M,Krauter J,Ganser A,Göhring G,Schlegelberger B,Schlenk RF,Döhner H,Döhner K

    更新日期:2013-07-04 00:00:00

  • Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs.

    abstract::Cyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune responses. The ability of CTX to promote the proliferation of effector T cells and abrogate the function of regulatory T cells (Tregs) has been described. In this study, we examined the effects of CTX treatment on dendritic cell (DC) sub...


    pub_type: 杂志文章


    authors: Nakahara T,Uchi H,Lesokhin AM,Avogadri F,Rizzuto GA,Hirschhorn-Cymerman D,Panageas KS,Merghoub T,Wolchok JD,Houghton AN

    更新日期:2010-06-03 00:00:00

  • The reversible binding of vinblastine to platelets: implications for therapy.

    abstract::The ability of platelets to adsorb vinblastine has been used to treat patients with immune thrombocytopenia. It is hypothesized that the drug-platelet complex is coated with antibody, taken up by macrophages which are then destroyed by the drug. We gave 16 courses of vinblastine-platelets to six patients with immune t...


    pub_type: 杂志文章


    authors: Kelton JG,McDonald JW,Barr RM,Walker I,Nicholson W,Neame PB,Hamid C,Wong TY,Hirsh J

    更新日期:1981-03-01 00:00:00

  • Use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous marrow transplantation for lymphoid malignancies.

    abstract::The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following autologous marrow transplantation for lymphoid malignancies was explored in a phase I/II dose escalation study. rhGM-CSF given as a 2-hour infusion daily for 14 days was well tolerated at doses up to 240 micrograms/m2/da...


    pub_type: 杂志文章


    authors: Nemunaitis J,Singer JW,Buckner CD,Hill R,Storb R,Thomas ED,Appelbaum FR

    更新日期:1988-08-01 00:00:00

  • Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients.

    abstract::A study in 121 infants with severe combined immunodeficiency (SCID) was performed to determine the prevalence of an engraftment by transplacentally acquired maternal T cells and to explore clinical and immunological findings related to this abnormality. Each newly diagnosed patient with SCID presenting with circulatin...


    pub_type: 杂志文章


    authors: Müller SM,Ege M,Pottharst A,Schulz AS,Schwarz K,Friedrich W

    更新日期:2001-09-15 00:00:00

  • Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity.

    abstract::We analyzed mutations of 7 vitamin K-dependent protein and cytochrome P450 2C9 genes in 45 patients and investigated whether any contribute to the large interpatient variability in the warfarin dose-effect relationship. Total clearance and daily dose, INR and INR/Cp, were used as pharmacokinetic and pharmacodynamic in...


    pub_type: 杂志文章


    authors: Shikata E,Ieiri I,Ishiguro S,Aono H,Inoue K,Koide T,Ohgi S,Otsubo K

    更新日期:2004-04-01 00:00:00

  • Microvascular abnormalities in sickle cell disease: a computer-assisted intravital microscopy study.

    abstract::The conjunctival microcirculation of 18 homozygous sickle cell disease (SCD) patients during steady-state, painful crisis, and postcrisis conditions was recorded on high-resolution videotapes using intravital microscopy. Selected videotape sequences were subsequently coded, frame-captured, studied, and blindly analyze...


    pub_type: 杂志文章


    authors: Cheung AT,Chen PC,Larkin EC,Duong PL,Ramanujam S,Tablin F,Wun T

    更新日期:2002-06-01 00:00:00

  • Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia.

    abstract::A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly ant...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Gmür J,von Felten A,Osterwalder B,Honegger H,Hörmann A,Sauter C,Deubelbeiss K,Berchtold W,Metaxas M,Scali G,Frick PG

    更新日期:1983-08-01 00:00:00

  • Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor.

    abstract::Although preclinical work with rapalogs suggests potential in treatment of multiple myeloma (MM), they have been less successful clinically. These drugs allostearically inhibit the mammalian target of rapamycin kinase primarily curtailing activity of the target of rapamycin complex (TORC)1. To assess if the mammalian ...


    pub_type: 杂志文章


    authors: Hoang B,Frost P,Shi Y,Belanger E,Benavides A,Pezeshkpour G,Cappia S,Guglielmelli T,Gera J,Lichtenstein A

    更新日期:2010-11-25 00:00:00

  • Ezrin is a target for oncogenic Kit mutants in murine erythroleukemia.

    abstract::The model of erythroleukemia caused by Spi-1/PU.1 transgenesis in mice is a multistage disease. A preleukemic step is characterized by an acute proliferation of proerythroblasts due to the arrest of differentiation provoked by Spi-1/PU.1. Later on, a blastic crisis occurs associated with somatic oncogenic mutations in...


    pub_type: 杂志文章


    authors: Monni R,Haddaoui L,Naba A,Gallais I,Arpin M,Mayeux P,Moreau-Gachelin F

    更新日期:2008-03-15 00:00:00

  • Activated protein C inhibits high mobility group box 1 signaling in endothelial cells.

    abstract::A pathogenic role for high-mobility group box 1 (HMGB1) protein has been postulated in severe sepsis. Activated protein C (APC) is the only drug approved by the Food and Drug Administration for severe sepsis; however, its effect on HMGB1 signaling has never been investigated. Here, we monitored the effect of APC on th...


    pub_type: 杂志文章


    authors: Bae JS,Rezaie AR

    更新日期:2011-10-06 00:00:00

  • How I treat anticoagulated patients undergoing an elective procedure or surgery.

    abstract::The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the us...


    pub_type: 杂志文章,评审


    authors: Spyropoulos AC,Douketis JD

    更新日期:2012-10-11 00:00:00

  • iNKT and memory B-cell alterations in HHV-8 multicentric Castleman disease.

    abstract::Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi sarcoma (KS) and multicentric Castleman disease (MCD), a life-threatening, virally induced B-cell lymphoproliferative disorder. HHV-8 is a B-lymphotropic γ-herpesvirus closely related to the Epstein-Barr virus (EBV). Invariant natural killer T (iNKT) cells a...


    pub_type: 杂志文章


    authors: Sbihi Z,Dossier A,Boutboul D,Galicier L,Parizot C,Emarre A,Hoareau B,Dupin N,Marcelin AG,Oudin A,Fieschi C,Agbalika F,Autran B,Oksenhendler E,Carcelain G

    更新日期:2017-02-16 00:00:00

  • Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder.

    abstract::Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by deplet...


    pub_type: 杂志文章


    authors: Vie H,Chevalier S,Garand R,Moisan JP,Praloran V,Devilder MC,Moreau JF,Soulillou JP

    更新日期:1989-07-01 00:00:00

  • Fev regulates hematopoietic stem cell development via ERK signaling.

    abstract::Reprogramming of somatic cells to desired cell types holds great promise in regenerative medicine. However, production of transplantable hematopoietic stem cells (HSCs) in vitro by defined factors has not yet been achieved. Therefore, it is critical to fully understand the molecular mechanisms of HSC development in vi...


    pub_type: 杂志文章


    authors: Wang L,Liu T,Xu L,Gao Y,Wei Y,Duan C,Chen GQ,Lin S,Patient R,Zhang B,Hong D,Liu F

    更新日期:2013-07-18 00:00:00

  • Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78.

    abstract::One hundred fifty-one children with acute myelogenous leukemia (AML) entered the cooperative study BFM-78 between December 1978 and October 1982. The initial therapy consisted of an intensive induction and consolidation regimen over eight weeks with seven different drugs and cranial irradiation. It was followed by mai...


    pub_type: 临床试验,杂志文章


    authors: Creutzig U,Ritter J,Riehm H,Langermann HJ,Henze G,Kabisch H,Niethammer D,Jürgens H,Stollmann B,Lasson U

    更新日期:1985-02-01 00:00:00

  • A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo.

    abstract::For activation T cells engage antigen-presenting cells (APCs) in lymphatic tissues. The contact duration and kinetics (static versus dynamic) vary considerably in different model systems; however, it is unclear whether T cells, APCs, or the environment are responsible for the observed discrepancies. Using 3-D collagen...


    pub_type: 杂志文章


    authors: Gunzer M,Weishaupt C,Hillmer A,Basoglu Y,Friedl P,Dittmar KE,Kolanus W,Varga G,Grabbe S

    更新日期:2004-11-01 00:00:00

  • Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations.

    abstract::Two patients with progressive hairy cell leukemia following splenectomy were treated with low-dose daily chlorambucil. Both had an objective hematologic response as determined by a return to normal hematocrit and platelet count. This was also reflected in the mononuclear cell fraction by the normalization of cholester...


    pub_type: 杂志文章


    authors: Krigel R,Liebes LF,Pelle E,Silber R

    更新日期:1982-07-01 00:00:00

  • Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells.

    abstract::Endothelial cells (ECs) express 2 members of the cadherin family, VE and N-cadherin. Although VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE or N-cadherin leads to early fetal lethality suggesting that these cadherins play a nonredun...


    pub_type: 杂志文章


    authors: Giampietro C,Taddei A,Corada M,Sarra-Ferraris GM,Alcalay M,Cavallaro U,Orsenigo F,Lampugnani MG,Dejana E

    更新日期:2012-03-01 00:00:00

  • The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation.

    abstract::GVHD and tumor relapse are fundamental problems in allogeneic HSCT. Recent research has linked neovascularization to GVHD, tumor growth, and graft-versus-tumor (GVT) activity. Damage of the endothelium by the conditioning regimen provides the initiation stimulus for recruitment of donor-derived endothelial cells and t...


    pub_type: 杂志文章


    authors: Penack O,Socié G,van den Brink MR

    更新日期:2011-04-21 00:00:00

  • Monocytes stimulate fibroblastoid bone marrow stromal cells to produce multilineage hematopoietic growth factors.

    abstract::In previous studies we have found that monocytes produce soluble factors that stimulate human umbilical vein endothelial cells to produce granulocyte-macrophage colony-stimulating activity (CSA), burst-promoting activity (BPA), and megakaryocyte colony-stimulating activity (Meg-CSA) as well as factors that stimulate T...


    pub_type: 杂志文章


    authors: Broudy VC,Zuckerman KS,Jetmalani S,Fitchen JH,Bagby GC Jr

    更新日期:1986-08-01 00:00:00

  • Influence of plasma immunoglobulin level on antibody synthesis.

    abstract::In previous experimental animal studies it has been demonstrated that antibody depletion is not followed by increased antibody synthesis. To assess whether these results are conferrable to antibody-depleted humans, we measured free light chains (flcs) as markers of current antibody synthesis in 8 patients treated with...


    pub_type: 杂志文章


    authors: Goldammer A,Derfler K,Herkner K,Bradwell AR,Hörl WH,Haas M

    更新日期:2002-07-01 00:00:00

  • Macrophage colony-stimulating factor (CSF-1) gene expression in human T-lymphocyte clones.

    abstract::Macrophage colony stimulating factor (CSF-1) is one of several cytokines that control the differentiation, survival, and proliferation of monocytes and macrophages. A set of 11 human T-cell clones, chosen for their phenotypic diversity, were tested for their ability to express CSF-1 mRNA. After 5 hours of stimulation ...


    pub_type: 杂志文章


    authors: Hallet MM,Praloran V,Vié H,Peyrat MA,Wong G,Witek-Giannotti J,Soulillou JP,Moreau JF

    更新日期:1991-02-15 00:00:00

  • Inhibition of apoptosis by BCL2 prevents leukemic transformation of a murine myelodysplastic syndrome.

    abstract::Programmed cell death or apoptosis is a prominent feature of low-risk myelodysplastic syndromes (MDS), although the underlying mechanism remains controversial. High-risk MDS have less apoptosis associated with increased expression of the prosurvival BCL2-related proteins. To address the mechanism and pathogenic role o...


    pub_type: 杂志文章


    authors: Slape CI,Saw J,Jowett JB,Aplan PD,Strasser A,Jane SM,Curtis DJ

    更新日期:2012-09-20 00:00:00

  • Characterization of a monoclonal antibody having selective reactivity with normal and neoplastic plasma cells.

    abstract::A myeloma cell-reactive monoclonal antibody (MoAb), MM4, was generated from BALB/c mice immunized with alternate injections of cells from two human multiple myeloma (MM) cell lines. Screening by the enzyme-linked immunosorbent assay (ELISA) technique showed that MM4 reacted with human MM cell lines (7 of 7 positive), ...


    pub_type: 杂志文章


    authors: Tong AW,Lee JC,Stone MJ

    更新日期:1987-01-01 00:00:00

  • Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells.

    abstract::Human endothelial cells release two forms of a plasminogen activator-specific inhibitor: an active form that readily binds to and inhibits plasminogen activators and an inactive or latent form that has no anti-activator activity but which can be activated by denaturation. Latent and active forms of plasminogen activat...


    pub_type: 杂志文章


    authors: Levin EG

    更新日期:1986-05-01 00:00:00

  • Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells.

    abstract::Humans and mice with impaired perforin-dependent cytotoxic function may develop excessive T-cell activation and the fatal disorder hemophagocytic lymphohistiocytosis (HLH) after infection. Though cytotoxic lymphocytes can kill antigen-presenting cells, the physiological mechanism of perforin-mediated immune regulation...


    pub_type: 杂志文章


    authors: Terrell CE,Jordan MB

    更新日期:2013-06-27 00:00:00

  • Evidence for separate calcium-signaling P2T and P2U purinoceptors in human megakaryocytic Dami cells.

    abstract::Recently (J Pharmacol Exp Ther 261:580, 1992), we have shown that K562 leukemia cells express a calcium-signaling purinoceptor with characteristics of the P2T receptor subtype for adenosine diphosphate (ADP) previously found only in platelets. Because these results suggested that the P2T receptor may be an early marke...


    pub_type: 杂志文章


    authors: Murgo AJ,Contrera JG,Sistare FD

    更新日期:1994-03-01 00:00:00

  • Epitope specificity of CD44 for monoclonal antibody-dependent facilitation of marrow engraftment in a canine model.

    abstract::Primary graft rejection after marrow transplantation occurs more frequently in patients receiving HLA-haploidentical compared with HLA-identical sibling transplants. Both human and experimental animal data suggest that the cells responsible for this phenomenon are either host natural killer (NK) cells, T cells, or bot...


    pub_type: 杂志文章


    authors: Sandmaier BM,Storb R,Bennett KL,Appelbaum FR,Santos EB

    更新日期:1998-05-01 00:00:00

  • A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis.

    abstract::The hematopoietically expressed homeobox gene, Hhex, is a transcription factor that is important for development of definitive hematopoietic stem cells (HSCs) and B cells, and that causes T-cell leukemia when overexpressed. Here, we have used an Hhex inducible knockout mouse model to study the role of Hhex in adult he...


    pub_type: 杂志文章


    authors: Jackson JT,Nasa C,Shi W,Huntington ND,Bogue CW,Alexander WS,McCormack MP

    更新日期:2015-01-29 00:00:00