cAMP-induced secretion of endothelial von Willebrand factor is regulated by a phosphorylation/dephosphorylation switch in annexin A2.

Abstract:

:The large multimeric glyocoprotein von Willebrand factor (VWF) is a crucial component of both primary and secondary hemostasis. It is stored in secretory granules of vascular endothelial cells, the Weibel-Palade bodies (WPBs), and is released following stimulation by agonists that raise intracellular Ca(2+) or cyclic adenosine monophosphate (cAMP) levels. cAMP-induced exocytosis of WPBs requires protein kinase A activity, but downstream factors that are regulated by phosphorylation/dephosphorylation are not known. Here we identify the complex consisting of the lipid-binding protein annexin A2 (AnxA2) and S100A10 as such a factor. Knockdown and specific rescue approaches reveal that a functional AnxA2-S100A10 complex is required for the forskolin-induced, cAMP-dependent release of VWF. Forskolin triggers dephosphorylation of AnxA2 that is mediated by a calcineurin-like phosphatase and stabilizes the AnxA2-S100A10 complex, thereby promoting VWF release. Serine 11 of AnxA2 was identified as the target residue of this phosphorylation switch because a phosphomimicking mutation at this site prevents complex formation with S100A10 and, in contrast to wild-type or S11A-AnxA2, is unable to restore cAMP-dependent VWF secretion in AnxA2-depleted cells. Thus, complex formation of AnxA2 with S100A10 is a central regulatory mechanism in the acute release of VWF in response to cAMP-elevating agonists.

journal_name

Blood

journal_title

Blood

authors

Brandherm I,Disse J,Zeuschner D,Gerke V

doi

10.1182/blood-2012-12-475251

subject

Has Abstract

pub_date

2013-08-08 00:00:00

pages

1042-51

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2012-12-475251

journal_volume

122

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Reduction of the inhibitory antibody response to human factor VIII in hemophilia A mice by mutagenesis of the A2 domain B-cell epitope.

    abstract::Approximately 25% of patients with hemophilia A develop inhibitory antibodies after treatment with factor VIII. Most of the inhibitory activity is directed against epitopes in the A2 and C2 domains. Anti-A2 inhibitory antibodies recognize a 25-residue segment bounded by R484-I508. Several antigenic residues in this se...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-11-3891

    authors: Parker ET,Healey JF,Barrow RT,Craddock HN,Lollar P

    更新日期:2004-08-01 00:00:00

  • Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii.

    abstract::The activation of murine dendritic cells by Toxoplasma gondii has recently been shown to depend on a parasite protein that signals through the chemokine receptor CCR5. Here we demonstrate that this molecule, cyclophilin-18 (C-18), is an inhibitor of HIV-1 cell fusion and infection with cell-free virus. T gondii C-18 e...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-04-1096

    authors: Golding H,Aliberti J,King LR,Manischewitz J,Andersen J,Valenzuela J,Landau NR,Sher A

    更新日期:2003-11-01 00:00:00

  • Lethal autoimmune hemolytic anemia in CD47-deficient nonobese diabetic (NOD) mice.

    abstract::The glycoprotein CD47 (integrin-associated protein, IAP) is present on the surface of virtually all cells, including red blood cells (RBCs). CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein alpha (SIRPalpha). In this manner mild reactivity of wild-type RBCs with ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.10.3500

    authors: Oldenborg PA,Gresham HD,Chen Y,Izui S,Lindberg FP

    更新日期:2002-05-15 00:00:00

  • Production of chemokines, interleukin-8 and monocyte chemoattractant protein-1, during monocyte: endothelial cell interactions.

    abstract::The extravasation of leukocytes from the lumen of the vessel to a site of inflammation requires specific binding events. The interaction of leukocytes with endothelium, via specific receptors, may provide intracellular signals that activate extravasating cells. In the present study, we have investigated the production...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lukacs NW,Strieter RM,Elner V,Evanoff HL,Burdick MD,Kunkel SL

    更新日期:1995-10-01 00:00:00

  • Organ-derived dendritic cells have differential effects on alloreactive T cells.

    abstract::Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-06-096602

    authors: Kim TD,Terwey TH,Zakrzewski JL,Suh D,Kochman AA,Chen ME,King CG,Borsotti C,Grubin J,Smith OM,Heller G,Liu C,Murphy GF,Alpdogan O,van den Brink MR

    更新日期:2008-03-01 00:00:00

  • Mild and severe beta-thalassemia among homozygotes from Turkey: identification of the types by hybridization of amplified DNA with synthetic probes.

    abstract::Through the procedure of gene amplification combined with hybridization to synthetic 19 base pair (bp) oligonucleotide probes, it has been possible to identify nine different mutations in the DNA of 47 subjects from Turkey and Northern Cyprus with a beta-thalassemia homozygosity. The IVS-I nucleotide (nt) 110 G----A a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Diaz-Chico JC,Yang KG,Stoming TA,Efremov DG,Kutlar A,Kutlar F,Aksoy M,Altay C,Gurgey A,Kilinc Y

    更新日期:1988-01-01 00:00:00

  • Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens.

    abstract::The extracellular presence of endotoxin-free heat shock protein 70 (HSP70) enhances the rate and capacity of macrophage-mediated phagocytosis at 6 times the basal rate. It is protein-specific, dose- and time-dependent and involves the internalization of inert microspheres, Gram-positive and -negative bacteria and fung...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-06-2559

    authors: Wang R,Kovalchin JT,Muhlenkamp P,Chandawarkar RY

    更新日期:2006-02-15 00:00:00

  • Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells.

    abstract::Thioredoxin (Trx) is a ubiquitous protein disulfide oxidoreductase with antioxidant, cytokine, and chemotactic properties. Previously, we showed that Trx, in synergy with interleukin 1 (IL-1), IL-2, IL-4, tumor necrosis factor alpha (TNF-alpha), and CD40-ligation induced S-phase entry and mitosis in normal B cells and...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Nilsson J,Söderberg O,Nilsson K,Rosén A

    更新日期:2000-02-15 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...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Levin EG

    更新日期:1986-05-01 00:00:00

  • Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).

    abstract::The reported outcome of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched family members has been inconsistent. The object of this study was to evaluate the true impact of HLA-mismatch by using recent data from a homogenous population, excluding HSCT procedures that used graft manipulations, and by co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-02-0430

    authors: Kanda Y,Chiba S,Hirai H,Sakamaki H,Iseki T,Kodera Y,Karasuno T,Okamoto S,Hirabayashi N,Iwato K,Maruta A,Fujimori Y,Furukawa T,Mineishi S,Matsuo K,Hamajima N,Imamura M

    更新日期:2003-08-15 00:00:00

  • Approach to the treatment of multiple myeloma: a clash of philosophies.

    abstract::In this Perspective, we summarize some of the most contentious issues surrounding diagnosis and treatment of myeloma. We outline how a fundamental clash of philosophies, cure versus control, may be at the heart of many of the controversies. From the very definition of the disease to risk stratification to the validity...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-06-297853

    authors: Rajkumar SV,Gahrton G,Bergsagel PL

    更新日期:2011-09-22 00:00:00

  • Granulocyte colony-stimulating factor induction of normal human bone marrow progenitors results in neutrophil-specific gene expression.

    abstract::We have used a combination of hematopoietic growth factors to induce in vitro granulocytic maturation. A fraction of marrow cells enriched for hematopoietic progenitor cells (CD34+, HLA-DR+) was isolated from normal human bone marrow by monoclonal antibody staining and fluorescence-activated cell sorting. Cells were c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Berliner N,Hsing A,Graubert T,Sigurdsson F,Zain M,Bruno E,Hoffman R

    更新日期:1995-02-01 00:00:00

  • HHEX promotes myeloid transformation in cooperation with mutant ASXL1.

    abstract::Additional sex combs-like 1 (ASXL1), an epigenetic modulator, is frequently mutated in myeloid neoplasms. Recent analyses of mutant ASXL1 conditional knockin (ASXL1-MT-KI) mice suggested that ASXL1-MT alone is insufficient for myeloid transformation. In our previous study, we used retrovirus-mediated insertional mutag...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019004613

    authors: Takeda R,Asada S,Park SJ,Yokoyama A,Becker HJ,Kanai A,Visconte V,Hershberger C,Hayashi Y,Yonezawa T,Tamura M,Fukushima T,Tanaka Y,Fukuyama T,Matsumoto A,Yamasaki S,Nakai K,Yamazaki S,Inaba T,Shibata T,Inoue D,Ho

    更新日期:2020-10-01 00:00:00

  • Interleukin 4-induced gene 1 is activated in primary mediastinal large B-cell lymphoma.

    abstract::The molecular markers that distinguish primary mediastinal large B-cell lymphoma (PMBL) from nonmediastinal diffuse large B-cell lymphomas (NM-DLBLs) remain to be identified. Using cDNA representational difference analysis to compare PMBL and NM-DLBL transcripts, we isolated a cDNA fragment homologous to the mouse B-c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-07-2215

    authors: Copie-Bergman C,Boulland ML,Dehoulle C,Möller P,Farcet JP,Dyer MJ,Haioun C,Roméo PH,Gaulard P,Leroy K

    更新日期:2003-04-01 00:00:00

  • Myeloblastin is an Myb target gene: mechanisms of regulation in myeloid leukemia cells growth-arrested by retinoic acid.

    abstract::A pivotal role has been assigned to Myb in the control of myeloid cell growth. Although Myb is a target of retinoic acid, little is known about the mechanisms by which it may contribute to induced growth arrest in leukemia cells. Indeed, few Myb target genes are known to be linked to proliferation. Myeloblastin is inv...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.8.2449

    authors: Lutz PG,Houzel-Charavel A,Moog-Lutz C,Cayre YE

    更新日期:2001-04-15 00:00:00

  • Extracellular ubiquitin inhibits the TNF-alpha response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness.

    abstract::Ubiquitin is suggested to play a key role in essential intracellular functions, such as heat shock response, protein breakdown, and regulation of immune responses. Ubiquitin has also been detected in the extracellular space, but the function and biologic significance is unclear. We describe a new function of extracell...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0918

    authors: Majetschak M,Krehmeier U,Bardenheuer M,Denz C,Quintel M,Voggenreiter G,Obertacke U

    更新日期:2003-03-01 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

  • Altered control of self-reactive IgG by autologous IgM in patients with warm autoimmune hemolytic anemia.

    abstract::Warm autoimmune hemolytic anemia (WAIHA) is characterized by an accelerated clearance of red blood cells (RBCs) associated with the presence of anti-RBC immunoglobulin (Ig)G autoantibodies. In the present study, we analyzed the self-reactive IgG and IgM antibody repertoires of patients with WAIHA using a technique of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Stahl D,Lacroix-Desmazes S,Heudes D,Mouthon L,Kaveri SV,Kazatchkine MD

    更新日期:2000-01-01 00:00:00

  • Transforming growth factor-beta regulates c-kit message stability and cell-surface protein expression in hematopoietic progenitors.

    abstract::The cell-surface receptor c-kit and its cognate ligand stem-cell factor (SCF) or steel factor (SLF) are important for the maintenance of hematopoiesis both in vitro and in vivo. Transforming growth factor-beta (TGF-beta) has been shown to be a potent inhibitor of SLF-mediated synergistic growth of murine Lin-Sca-1+ pr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dubois CM,Ruscetti FW,Stankova J,Keller JR

    更新日期:1994-06-01 00:00:00

  • Tumor cell heterogeneity in multiple myeloma: antigenic, morphologic, and functional studies of cells from blood and bone marrow.

    abstract::Tumor cells from six patients with immunoglobulin G (IgG) multiple myeloma were analyzed for surface antigens, cytoplasmic paraprotein, morphology, and response to various culture conditions. The tumor marker was the paraprotein idiotype. Low numbers of tumor cells were found in the blood of most of the patients. In s...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: King MA,Nelson DS

    更新日期:1989-05-15 00:00:00

  • Deletion of the core region of 5' HS2 of the mouse beta-globin locus control region reveals a distinct effect in comparison with human beta-globin transgenes.

    abstract::The beta-globin locus control region (LCR) is a large DNA element that is required for high-level expression of beta-like globin genes from the endogenous mouse locus or in transgenic mice carrying the human beta-globin locus. The LCR encompasses 6 DNaseI hypersensitive sites (HSs) that bind transcription factors. The...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-06-2308

    authors: Hu X,Bulger M,Bender MA,Fields J,Groudine M,Fiering S

    更新日期:2006-01-15 00:00:00

  • Induction of monocytic differentiation and tumorigenicity by v-Ha-ras in differentiation arrested hematopoietic cells.

    abstract::Activated ras genes are often associated with human myeloid leukemias with a monocytic differentiated phenotype. To investigate the role of the activated ras gene in leukemogenesis, a myeloid nontumorigenic cell line (FDC-P1) was infected with a selectable retroviral vector carrying the v-Ha-ras gene (H1neo). Infected...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hibi S,Löhler J,Friel J,Stocking C,Ostertag W

    更新日期:1993-04-01 00:00:00

  • Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression.

    abstract::Type I interferon (IFNalpha/beta) plays a complex role in HIV-1 infection and has been proposed alternately to have roles in either disease protection or progression. Although IFNalpha/beta plays crucial roles in regulating monocytes and dendritic cells, responsiveness of these cells to IFNalpha/beta in HIV-1 infectio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-11-190231

    authors: Hardy GA,Sieg SF,Rodriguez B,Jiang W,Asaad R,Lederman MM,Harding CV

    更新日期:2009-05-28 00:00:00

  • Thrombopoietin signal transduction in purified murine megakaryocytes.

    abstract::Thrombopoietin (TPO) is a recently cloned cytokine that binds to its receptor, Mpl, and promotes hematopoietic expansion and maturation, primarily of the megakaryocyte lineage. The signaling pathways responsible for these events are thought to involve the Janus family of nonreceptor tyrosine kinases (JAKs) and the sig...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Drachman JG,Sabath DF,Fox NE,Kaushansky K

    更新日期:1997-01-15 00:00:00

  • Interleukin-12 (IL-12) production in whole blood cultures from human immunodeficiency virus-infected individuals studied in relation to IL-10 and prostaglandin E2 production.

    abstract::The role of interleukin-12 (IL-12) in Th1 cell differentiation is well established. The heterodimer p70, composed of a p40 and a p35 chain, is the biologically active form. IL-12 production by human monocytes is enhanced by interferon-gamma (IFN-gamma) and inhibited by IL-10 and prostaglandin E2 (PGE2). Peripheral blo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Meyaard L,Hovenkamp E,Pakker N,van der Pouw Kraan TC,Miedema F

    更新日期:1997-01-15 00:00:00

  • Angiostatic activity of the antitumor cytokine interleukin-21.

    abstract::Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-09-113878

    authors: Castermans K,Tabruyn SP,Zeng R,van Beijnum JR,Eppolito C,Leonard WJ,Shrikant PA,Griffioen AW

    更新日期:2008-12-15 00:00:00

  • Intragenic Factor IX restriction site polymorphism in hemophilia B variants.

    abstract::This study includes 47 normal subjects and 25 hemophilia B patients without inhibitor(s), showing different factor IX coagulant activity and antigen levels. Genomic DNA, digested with various restriction endonucleases, was hybridized with two different factor IX probes, ie, the cDNA and the subgenomic probe for the in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hassan HJ,Orlando M,Leonardi A,Chelucci C,Guerriero R,Mannucci PM,Mariani G,Peschle C

    更新日期:1985-02-01 00:00:00

  • Immunologic abnormalities in myelofibrosis with activation of the complement system.

    abstract::Eighteen patients with agnogenic myeloid metaplasia with myelofibrosis were studied for clinical and laboratory evidence of immunologic dysfunction. Clinical findings included the presence of arthritis, vasculitis, and erythema nodosum. Laboratory abnormalities included the presence of circulating immune complexes, an...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Gordon BR,Coleman M,Kohen P,Day NK

    更新日期:1981-11-01 00:00:00

  • High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine.

    abstract::Although virtually all pediatric patients with acute myeloid leukemia (AML) achieve a complete remission after initial induction therapy, 30%-40% of patients will encounter a relapse and have a dismal prognosis. To prevent relapses, personalized treatment strategies are currently being developed, which target specific...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-03-276519

    authors: Bachas C,Schuurhuis GJ,Hollink IH,Kwidama ZJ,Goemans BF,Zwaan CM,van den Heuvel-Eibrink MM,de Bont ES,Reinhardt D,Creutzig U,de Haas V,Assaraf YG,Kaspers GJ,Cloos J

    更新日期:2010-10-14 00:00:00

  • Increased HIV-specific CD8+ T-cell cytotoxic potential in HIV elite controllers is associated with T-bet expression.

    abstract::Recent data suggest that CD8+ T-cell effector activity is an important component in the control of HIV replication in elite controllers (ECs). One critical element of CD8+ T-cell effector function and differentiation is the T-box transcription factor T-bet. In the present study, we assessed T-bet expression, together ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-12-322727

    authors: Hersperger AR,Martin JN,Shin LY,Sheth PM,Kovacs CM,Cosma GL,Makedonas G,Pereyra F,Walker BD,Kaul R,Deeks SG,Betts MR

    更新日期:2011-04-07 00:00:00