The kringle stabilizes urokinase binding to the urokinase receptor.

Abstract:

:The structural basis of the interaction between single-chain urokinase-type plasminogen activator (scuPA) and its receptor (uPAR) is incompletely defined. Several observations indicated the kringle facilitates the binding of uPA to uPAR. A scuPA variant lacking the kringle (Delta K-scuPA) bound to soluble uPAR (suPAR) with the similar "on-rate" but with a faster "off-rate" than wild-type (WT)-scuPA. Binding of Delta K-scuPA, but not WT-scuPA, to suPAR was comparably inhibited by its growth factor domain (GFD) and amino-terminal fragment (ATF). ATF and WT-scuPA, but not GFD, scuPA lacking the GFD (Delta GFD-scuPA), or Delta K-scuPA reconstituted the isolated domains of uPAR. ATF completely inhibited the enzymatic activity of WT-scuPA-suPAR unlike comparable concentrations of GFD. Variants containing mutations that alter the charge, length, or flexibility of linker sequence (residues 43-49) between the GFD and the kringle displayed a lower affinity for uPAR, were unable to reconstitute uPAR domains, and their binding to uPAR was inhibited by GFD in the same manner as Delta K-scuPA. A scuPA variant in which the charged amino acids in the heparin binding site (HBS) in the kringle domain were mutated to alanines behaved like Delta K-scuPA, indicating that that the structure of the kringle as well as its interaction with the GFD govern receptor binding. These data demonstrate an important role for the kringle in stabilizing the binding of scuPA to uPAR.

journal_name

Blood

journal_title

Blood

authors

Bdeir K,Kuo A,Sachais BS,Rux AH,Bdeir Y,Mazar A,Higazi AA,Cines DB

doi

10.1182/blood-2003-03-0949

subject

Has Abstract

pub_date

2003-11-15 00:00:00

pages

3600-8

issue

10

eissn

0006-4971

issn

1528-0020

pii

2003-03-0949

journal_volume

102

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Dangerous small B-cell clones.

    abstract::The detection of a monoclonal immunoglobulin in serum or urine usually raises concerns about the size of the underlying B-cell-derived clone and possible systemic effects caused by its expansion. However, a small clone can synthesize a very toxic protein, producing devastating systemic damage and protean clinical pres...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2006-03-001164

    authors: Merlini G,Stone MJ

    更新日期:2006-10-15 00:00:00

  • The differentiation program of embryonic definitive hematopoietic stem cells is largely alpha4 integrin independent.

    abstract::Previous analyses of the roles of alpha4 integrins in hematopoiesis by other groups have led to conflicting evidence. alpha4 integrin mutant cells developing in [alpha4 integrin(-/-): wt] chimeric mice are not capable of completing lymphomyeloid differentiation, whereas conditional inactivation of alpha4 integrin in a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4209

    authors: Gribi R,Hook L,Ure J,Medvinsky A

    更新日期:2006-07-15 00:00:00

  • Definitive but not primitive hematopoiesis is impaired in jumonji mutant mice.

    abstract::A novel gene, jumonji was identified by a mouse gene trap strategy. The jumonji gene encodes a protein containing a putative DNA binding domain. The mice homozygous for jumonji gene with a BALB/cA genetic background show hypoplasia of the fetal liver and embryonic lethality, suggesting impaired hematopoiesis. In the p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kitajima K,Kojima M,Nakajima K,Kondo S,Hara T,Miyajima A,Takeuchi T

    更新日期:1999-01-01 00:00:00

  • FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma.

    abstract::Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide ...

    journal_title:Blood

    pub_type: 杂志文章,meta分析

    doi:10.1182/blood-2011-10-383380

    authors: Ma YP,van Leeuwen FE,Cooke R,Broeks A,Enciso-Mora V,Olver B,Lloyd A,Broderick P,Russell NS,Janus C,Ashworth A,Houlston RS,Swerdlow AJ

    更新日期:2012-01-26 00:00:00

  • Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells.

    abstract::Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-12-398115

    authors: Butler JM,Gars EJ,James DJ,Nolan DJ,Scandura JM,Rafii S

    更新日期:2012-08-09 00:00:00

  • A1, a Bcl-2 family member, prolongs cell survival and permits myeloid differentiation.

    abstract::A1, a bcl-2 family member, has been identified as a hematopoietic-specific, early inducible gene. In this study it is shown that stable transfection of A1 into an interleukin-3 (IL-3)-dependent myeloid precursor cell line, 32D c13, leads to a retardation of IL-3 withdrawal-induced cell death similar to that observed w...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lin EY,Orlofsky A,Wang HG,Reed JC,Prystowsky MB

    更新日期:1996-02-01 00:00:00

  • Validation of the high-dose heparin confirmatory step for the diagnosis of heparin-induced thrombocytopenia.

    abstract::The diagnosis of heparin-induced thrombocytopenia (HIT) requires detection of antibodies to the heparin/platelet factor 4 (PF4) complexes via enzyme-linked immunosorbent assay. Addition of excess heparin to the sample decreases the optical density by 50% or more and confirms the presence of these antibodies. One hundr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-01-262659

    authors: Whitlatch NL,Kong DF,Metjian AD,Arepally GM,Ortel TL

    更新日期:2010-09-09 00:00:00

  • Vascular endothelial growth factor-A induces plaque expansion in ApoE knock-out mice by promoting de novo leukocyte recruitment.

    abstract::Vascular endothelial growth factor-A is widely used in clinical trials for the treatment of cardiac ischemia. VEGF-A was recently suggested to act in a proinflammatory manner, which could aggravate adjacent atherogenesis in VEGF-A-based therapy. To assess potential bystander effects, VEGF-A was focally overexpressed i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-07-031773

    authors: Lucerna M,Zernecke A,de Nooijer R,de Jager SC,Bot I,van der Lans C,Kholova I,Liehn EA,van Berkel TJ,Yla-Herttuala S,Weber C,Biessen EA

    更新日期:2007-01-01 00:00:00

  • Two types of murine CD34 mRNA generated by alternative splicing.

    abstract::To characterize and clarify the function of CD34 antigen experimentally, we isolated two types of CD34 mRNA from a cDNA library of murine stromal cell line, PA-6 stimulated with lipopolysaccharide (LPS) and 12-o-tetra-decanoylphorbol 13-acetate (TPA) using a human CD34 probe. In addition to the clone (open reading fra...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Suda J,Sudo T,Ito M,Ohno N,Yamaguchi Y,Suda T

    更新日期:1992-05-01 00:00:00

  • Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells.

    abstract::Activation of intracellular signaling pathways is important for cellular transformation and tumorigenesis. The nonreceptor tyrosine kinases Jak1 and Jak3, which bind to the v-Abl oncoprotein, are constitutively activated in cells transformed with the Abelson murine leukemia virus. A mutant of p160 v-Abl lacking the Ja...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v100.3.966

    authors: Oki S,Limnander A,Danial NN,Rothman PB

    更新日期:2002-08-01 00:00:00

  • A clinical study of the lupus anticoagulant.

    abstract::Eighty-three patients with circulating anticoagulants were studied at The New York Hospital. The lupus-type anticoagulant, an inhibitor of the prothrombin activator complex, was demonstrated in 58 patients. The inhibitor was identified using the blood and tissue thromboplastin inhibition tests. Inhibition by the lupus...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Schleider MA,Nachman RL,Jaffe EA,Coleman M

    更新日期:1976-10-01 00:00:00

  • G-protein-gated inwardly rectifying potassium channels regulate ADP-induced cPLA2 activity in platelets through Src family kinases.

    abstract::ADP-induced TXA2 generation requires the costimulation of P2Y1, P2Y12, and the GPIIb/IIIa receptors. Signaling events downstream of the P2Y receptors that contribute to ADP-induced TXA2 generation have not been clearly delineated. In this study, we have investigated the role of G-protein-gated inwardly rectifying pota...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-03-010330

    authors: Shankar H,Kahner BN,Prabhakar J,Lakhani P,Kim S,Kunapuli SP

    更新日期:2006-11-01 00:00:00

  • Administration of recombinant human interleukin-7 alters the frequency and number of myeloid progenitor cells in the bone marrow and spleen of mice.

    abstract::The administration of greater than or equal to 5 micrograms interleukin-7 (IL-7) twice a day to mice for 4 to 7 days increased by twofold to fivefold the total number of splenic and peripheral blood leukocytes, but did not appreciably increase bone marrow (BM) cellularity. This regimen of IL-7 administration also resu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Damia G,Komschlies KL,Faltynek CR,Ruscetti FW,Wiltrout RH

    更新日期:1992-03-01 00:00:00

  • Identification of a restriction fragment length polymorphism involving the oncogene ETS-1 on chromosome 11q23.

    abstract::Twenty four samples of DNA from 23 unrelated individuals were analyzed for the presence of a novel restriction fragment length polymorphism (RFLP) involving the proto-oncogene ETS-1 at an Xba I site. Four samples from unrelated individuals lacked an Xba I site, giving rise to a longer restriction fragment detectable b...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Savage PD,Hanson CA,Kersey JH

    更新日期:1987-07-01 00:00:00

  • Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors.

    abstract::The MLL gene located at 11q23 is frequently disrupted by chromosomal translocation in a wide spectrum of newly diagnosed acute leukemias. Recently, it has become apparent that the MLL gene is very frequently disrupted by chromosomal translocations in patients with secondary leukemias associated with chemotherapeutic r...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Aplan PD,Chervinsky DS,Stanulla M,Burhans WC

    更新日期:1996-04-01 00:00:00

  • Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis.

    abstract::In eighty-three patients with confirmed deep vein thrombosis, the fibrinolytic system was studied before and after a 10-minute venous occlusion. Blood was collected at least 3 months after the last acute episode, and PAI-1 antigen and activity, as well as tissue-type plasminogen activator (t-PA) antigen, urokinase-typ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nguyen G,Horellou MH,Kruithof EK,Conard J,Samama MM

    更新日期:1988-08-01 00:00:00

  • Superficial venous thrombosis: recognizing the risk.

    abstract::In this issue of Blood, Roach and colleagues show that individuals with prior superficial venous thrombosis are at increased risk of developing venous thromboembolism when exposed to acquired clinical risk factors. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2013-11-537019

    authors: Bates SM

    更新日期:2013-12-19 00:00:00

  • Human T cells expressing two additional receptors (TETARs) specific for HIV-1 recognize both epitopes.

    abstract::Adoptive TCR transfer against rapidly mutating targets, such as HIV-1 or cancer, must counteract corresponding immune escape. Hence, we generated T cells expressing two additional receptors (TETARs) specific for HIV-1 by TCR mRNA electroporation. An HLA-A2-restricted gag-specific TCR and an HLA-B13-restricted nef-spec...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-04-347005

    authors: Hofmann C,Höfflin S,Hückelhoven A,Bergmann S,Harrer E,Schuler G,Dörrie J,Schaft N,Harrer T

    更新日期:2011-11-10 00:00:00

  • The rhesus macaque as an animal model for hemophilia B gene therapy.

    abstract::We have determined the 2905 nucleotide sequence of the rhesus macaque factor IX complementary DNA (cDNA) and found it to be greater than 95% identical to that of the human factor IX cDNA. The cDNA has a large 3' untranslated region like the human cDNA, but unlike the human cDNA has two polyadenylation sites 224 nucleo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lozier JN,Metzger ME,Donahue RE,Morgan RA

    更新日期:1999-03-15 00:00:00

  • High-dose cyclophosphamide for refractory autoimmune hemolytic anemia.

    abstract::High-dose cyclophosphamide, without stem cell rescue, has been used successfully to treat aplastic anemia and other autoimmune disorders. To determine the safety and efficacy of high-dose cyclophosphamide among patients with severe refractory autoimmune hemolytic anemia, we treated 9 patients with cyclophosphamide (50...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2002-01-0087

    authors: Moyo VM,Smith D,Brodsky I,Crilley P,Jones RJ,Brodsky RA

    更新日期:2002-07-15 00:00:00

  • High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells.

    abstract::Studies on the role of inflammation in cardiovascular disease focus on surrogate markers like plasma levels of C-reactive protein or interleukins that are affected by several factors. In this study we employ an approach in which the inflammatory mRNA profile of leucocytes is measured directly in a multigene system. We...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-08-3283

    authors: Wettinger SB,Doggen CJ,Spek CA,Rosendaal FR,Reitsma PH

    更新日期:2005-03-01 00:00:00

  • Identification of amino acid residues that are crucial for FXIII-A intersubunit interactions and stability.

    abstract::Coagulation factor XIII (FXIII) is the main stabilizer of the fibrin clot. It circulates in plasma as a tetramer of two A-subunits and two B-subunits. Under physiological conditions, FXIII-A exists as a dimer (FXIII-A2). The interactions between the FXIII-A-subunits that stabilize the FXIII-A2 dimer are not fully unde...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019002127

    authors: Li B,Kohler HP,Schroeder V

    更新日期:2020-01-09 00:00:00

  • Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation.

    abstract::Interleukin-25 (IL-25) is a recently described T helper 2 (T(H)2) cell-derived cytokine that belongs to the IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T-cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-09-2817

    authors: Ikeda K,Nakajima H,Suzuki K,Kagami S,Hirose K,Suto A,Saito Y,Iwamoto I

    更新日期:2003-05-01 00:00:00

  • STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90alpha and beta in multiple myeloma cells, which critically contribute to tumor-cell survival.

    abstract::The combined blockade of the IL-6R/STAT3 and the MAPK signaling pathways has been shown to inhibit bone marrow microenvironment (BMM)-mediated survival of multiple myeloma (MM) cells. Here, we identify the molecular chaperones heat shock proteins (Hsp) 90alpha and beta as target genes of both pathways. The siRNA-media...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-05-024372

    authors: Chatterjee M,Jain S,Stühmer T,Andrulis M,Ungethüm U,Kuban RJ,Lorentz H,Bommert K,Topp M,Krämer D,Müller-Hermelink HK,Einsele H,Greiner A,Bargou RC

    更新日期:2007-01-15 00:00:00

  • Role of arginine residues in the coagulant activity of high molecular weight kininogen.

    abstract::High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chang JJ,Scott CF,Colman RW

    更新日期:1986-03-01 00:00:00

  • Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system.

    abstract::Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemia (APL) with minimal toxicity and apoptosis in APL-derived NB4 cells at low (1 to 2 micromol/L) concentration. We examined the basis for NB4 cell sensitivity to As2O3 to identify experimental conditions that would render other malignant ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dai J,Weinberg RS,Waxman S,Jing Y

    更新日期:1999-01-01 00:00:00

  • Cytolytically inactive terminal complement complex causes transendothelial migration of polymorphonuclear leukocytes in vitro and in vivo.

    abstract::Intravital microscopy was used to monitor leukocyte traffic across rat mesenteric postcapillary venules induced by the inactive terminal complement (C) complex (iTCC) topically applied to ileal mesentery. Leukocytes started rolling within 15 minutes from the administration of iTCC, and by 1 hour they adhered almost co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.1.185

    authors: Dobrina A,Pausa M,Fischetti F,Bulla R,Vecile E,Ferrero E,Mantovani A,Tedesco F

    更新日期:2002-01-01 00:00:00

  • The identification of fibrosis-driving myofibroblast precursors reveals new therapeutic avenues in myelofibrosis.

    abstract::Myofibroblasts are fibrosis-driving cells and are well characterized in solid organ fibrosis, but their role and cellular origin in bone marrow fibrosis remains obscure. Recent work has demonstrated that Gli1+ and LepR+ mesenchymal stromal cells (MSCs) are progenitors of fibrosis-causing myofibroblasts in the bone mar...

    journal_title:Blood

    pub_type: 杂志文章,评审

    doi:10.1182/blood-2018-02-834820

    authors: Kramann R,Schneider RK

    更新日期:2018-05-10 00:00:00

  • The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2.

    abstract::The CXC-chemokines interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2), and melanoma growth-stimulatory activity (MGSA) are chemoattractants with high selectivity for neutrophils. Although IL-8 has been shown to act as an extremely potent mediator, reports on NAP-2 and MGSA are still contradictory. Here we s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ludwig A,Petersen F,Zahn S,Götze O,Schröder JM,Flad HD,Brandt E

    更新日期:1997-12-01 00:00:00

  • Immunocytochemical study of the binding of fibrinogen and thrombospondin to ADP- and thrombin-stimulated human platelets.

    abstract::We have used immunogold staining to locate thrombospondin (TSP) on thrombin-activated human platelets, and have compared its distribution with that of fibrinogen (or fibrin) on thrombin- and ADP-stimulated platelets. To do this, isolated platelets were incubated with monospecific antibodies to TSP or fibrinogen (fib) ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hourdillé P,Hasitz M,Belloc F,Nurden AT

    更新日期:1985-04-01 00:00:00