AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties.

Abstract:

:Adhesive forces at endothelial cell-cell borders maintain vascular integrity. cAMP enhances barrier properties and controls cellular processes through protein kinase A bound to A-kinase anchoring proteins (AKAPs). It also activates exchange protein directly activated by cAMP (Epac1), an exchange factor for Ras-related protein 1 (Rap1) GTPases that promotes cadherin- and integrin-mediated adhesion through effects on the actin cytoskeleton. We demonstrate that AKAP9 facilitates the microtubule polymerization rate in endothelial cells, interacts with Epac1, and is required for Epac1-stimulated microtubule growth. AKAP9 is not required for maintaining barrier properties under steady-state conditions. Rather, it is essential when the cell is challenged to make new adhesive contacts, as is the case when Epac activation enhances barrier function through a mechanism that, surprisingly, requires integrin adhesion at cell-cell contacts. In the present study, defects in Epac-induced responses in AKAP9-silenced cells were evident despite an intact Epac-induced increase in Rap activation, cortical actin, and vascular endothelial-cadherin adhesion. We describe a pathway that integrates Epac-mediated signals with AKAP9-dependent microtubule dynamics to coordinate integrins at lateral borders.

journal_name

Blood

journal_title

Blood

authors

Sehrawat S,Ernandez T,Cullere X,Takahashi M,Ono Y,Komarova Y,Mayadas TN

doi

10.1182/blood-2010-02-268870

subject

Has Abstract

pub_date

2011-01-13 00:00:00

pages

708-18

issue

2

eissn

0006-4971

issn

1528-0020

pii

blood-2010-02-268870

journal_volume

117

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling.

    abstract::In haploidentical transplantation, the mismatched haplotype of the donor can originate from either of the parents. We refer to such mismatched haplotypes as noninherited maternal antigens (NIMA haplotype) or noninherited paternal antigens (NIPA haplotype). To determine whether exposure to maternal HLA antigens benefit...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.5.1572

    authors: van Rood JJ,Loberiza FR Jr,Zhang MJ,Oudshoorn M,Claas F,Cairo MS,Champlin RE,Gale RP,Ringdén O,Hows JM,Horowitz MH

    更新日期:2002-03-01 00:00:00

  • Production of colony-stimulating activity by human natural killer cells: analysis of the conditions that influence the release and detection of colony-stimulating activity.

    abstract::Highly purified natural killer (NK) cell suspensions were tested for their capacity to release colony-stimulating activity (CSA) in vitro. NK cell suspensions comprised primarily CD16+ cells and were devoid of CD3+ T cells, CD15+ monocytes, and of B cells. CSA was detected in the NK cell supernatants and sustained the...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Pistoia V,Zupo S,Corcione A,Roncella S,Matera L,Ghio R,Ferrarini M

    更新日期:1989-07-01 00:00:00

  • Effects of mixed hematopoietic chimerism in a mouse model of bone marrow transplantation for sickle cell anemia.

    abstract::Sickle cell anemia (SCA) is an inherited disorder of beta-globin, resulting in red blood cell rigidity, anemia, painful crises, organ infarctions, and reduced life expectancy. Allogeneic blood or marrow transplantation (BMT) can cure SCA but is associated with an 8% to 10% mortality rate, primarily from complications ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.12.3960

    authors: Iannone R,Luznik L,Engstrom LW,Tennessee SL,Askin FB,Casella JF,Kickler TS,Goodman SN,Hawkins AL,Griffin CA,Noffsinger L,Fuchs EJ

    更新日期:2001-06-15 00:00:00

  • Zinc protoporphyrin in anemia of chronic disorders.

    abstract::Hematofluorometric determination of zinc protoporphyrin (ZPP) is a screening method for the assessment of iron deficiency (ID). Chronic disorders are frequently accompanied by anemias of unclear origin, most probably caused by an impairment of iron metabolism. We investigated the relevance of ZPP for the detection of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hastka J,Lasserre JJ,Schwarzbeck A,Strauch M,Hehlmann R

    更新日期:1993-03-01 00:00:00

  • Immunoregulatory roles of versican proteolysis in the myeloma microenvironment.

    abstract::Myeloma immunosurveillance remains incompletely understood. We have demonstrated proteolytic processing of the matrix proteoglycan, versican (VCAN), in myeloma tumors. Whereas intact VCAN exerts tolerogenic activities through Toll-like receptor 2 (TLR2) binding, the immunoregulatory consequences of VCAN proteolysis re...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-03-705780

    authors: Hope C,Foulcer S,Jagodinsky J,Chen SX,Jensen JL,Patel S,Leith C,Maroulakou I,Callander N,Miyamoto S,Hematti P,Apte SS,Asimakopoulos F

    更新日期:2016-08-04 00:00:00

  • Liposomal Bcl-2 antisense oligonucleotides enhance proliferation, sensitize acute myeloid leukemia to cytosine-arabinoside, and induce apoptosis independent of other antiapoptotic proteins.

    abstract::The antiapoptotic proteins, Bcl-2 and Bcl-X(L), are expressed in most cases of acute myeloid leukemia (AML) and may contribute to drug resistance in AML. We tested the hypothesis that down-regulation of Bcl-2 alone by antisense oligodeoxynucleotides (Bcl-2-AS) induces apoptosis, even in the presence of other antiapopt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Konopleva M,Tari AM,Estrov Z,Harris D,Xie Z,Zhao S,López-Berestein G,Andreeff M

    更新日期:2000-06-15 00:00:00

  • Separation of blast cell and T-lymphocyte progenitors in the blood of patients with acute myeloblastic leukemia.

    abstract::The peripheral blood of acute myeloblastic leukemia (AML) patients often contains large numbers of two distinct cell populations, both capable of forming colonies in culture under similar conditions. The first population consists of the precursors of blast cells and has specificity for AML; the second population consi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Minden MD,Buick RN,McCulloch EA

    更新日期:1979-07-01 00:00:00

  • Dynamics of complement activation in aHUS and how to monitor eculizumab therapy.

    abstract::Atypical hemolytic-uremic syndrome (aHUS) is associated with genetic complement abnormalities/anti-complement factor H antibodies, which paved the way to treatment with eculizumab. We studied 44 aHUS patients and their relatives to (1) test new assays of complement activation, (2) verify whether such abnormality occur...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2014-02-558296

    authors: Noris M,Galbusera M,Gastoldi S,Macor P,Banterla F,Bresin E,Tripodo C,Bettoni S,Donadelli R,Valoti E,Tedesco F,Amore A,Coppo R,Ruggenenti P,Gotti E,Remuzzi G

    更新日期:2014-09-11 00:00:00

  • Synergy between imatinib and mycophenolic acid in inducing apoptosis in cell lines expressing Bcr-Abl.

    abstract::Bcr-Abl tyrosine kinase activity initiates a number of intracellular signaling cascades that result in leukemogenesis. Imatinib mesylate, a specific Bcr-Abl tyrosine kinase inhibitor, has been highly successful in the treatment of chronic myelogenous leukemia (CML). However, the emergence of imatinib resistance and th...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-10-3864

    authors: Gu JJ,Santiago L,Mitchell BS

    更新日期:2005-04-15 00:00:00

  • Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3.

    abstract::Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-beta superfamily, are a group of related proteins that are capable of inducing the formation of cartilage and bone but are now regarded as multifunctional cytokines. We show in this report a novel function of BMPs in hematopoietic cell...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kawamura C,Kizaki M,Yamato K,Uchida H,Fukuchi Y,Hattori Y,Koseki T,Nishihara T,Ikeda Y

    更新日期:2000-09-15 00:00:00

  • A prospective study of mitochondrial DNA copy number and risk of non-Hodgkin lymphoma.

    abstract::Mitochondrial DNA (mtDNA) copy number is increased in patients with chronic lymphocytic leukemia (CLL), in Burkitt lymphoma and Epstein-Barr virus-transformed lymphoblastoid cell lines, and in T cells activated via the T-cell receptor. We hypothesized that having a higher mtDNA copy number in peripheral white blood ce...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-05-157974

    authors: Lan Q,Lim U,Liu CS,Weinstein SJ,Chanock S,Bonner MR,Virtamo J,Albanes D,Rothman N

    更新日期:2008-11-15 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

  • An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab in relapsed/refractory patients with B-cell chronic lymphocytic leukemia.

    abstract::Although combination regimens have improved outcomes over monotherapy in chronic lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine, cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided synergistic cytotoxicity with effective clearing of minimal residual disease. Th...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2011-05-351833

    authors: Montillo M,Tedeschi A,Petrizzi VB,Ricci F,Crugnola M,Spriano M,Spedini P,Ilariucci F,Uziel L,Attolico I,Vismara E,De Blasio A,Zaccaria A,Morra E

    更新日期:2011-10-13 00:00:00

  • Comparison of in vitro growth characteristics of blast cell progenitors (CFU-L) in patients with myelodysplastic syndromes and acute myeloid leukemia.

    abstract::Current knowledge is inadequate to explain the different patterns of blast cell accumulation in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We compared the growth patterns of blast cell progenitors (CFU-L) in 23 patients with advanced MDS and 32 patients with de novo AML. Circulating blast progen...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Aul C,Gattermann N,Schneider W

    更新日期:1992-08-01 00:00:00

  • Functional study of lipids of PNH red cell membranes: susceptibility of liposomes to reactive lysis.

    abstract::Lipids extracted with chloroform-methanol from red blood cell membranes of 7 PNH and 13 control subjects were used for the preparation of liposomes, which were then examined with the reactive lysis test. PNH liposomes lysed to a higher extent than control liposomes as indicated by the higher dilution of the limiting c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tedesco F,Kahane I,Zanella A,Giovanetti AM,Sirchia G

    更新日期:1981-05-01 00:00:00

  • Protein S levels and the risk of venous thrombosis: results from the MEGA case-control study.

    abstract::In thrombophilic families, protein S deficiency is clearly associated with venous thrombosis. We aimed to determine whether the same holds true in a population-based case-control study (n = 5317). Subjects were regarded protein S deficient when protein S levels were < 2.5th percentile of the controls. Free and total p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-04-499335

    authors: Pintao MC,Ribeiro DD,Bezemer ID,Garcia AA,de Visser MC,Doggen CJ,Lijfering WM,Reitsma PH,Rosendaal FR

    更新日期:2013-10-31 00:00:00

  • Results of a phase 2 trial of an oral CXCR4 antagonist, mavorixafor, for treatment of WHIM syndrome.

    abstract::Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the CXCR4 gene. We report the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mavorixafor from a phase 2 open-label dose-escalatio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2020007197

    authors: Dale DC,Firkin F,Bolyard AA,Kelley M,Makaryan V,Gorelick KJ,Ebrahim T,Garg V,Tang W,Jiang H,Skerlj R,Beaussant Cohen S

    更新日期:2020-12-24 00:00:00

  • Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL.

    abstract::The FOXP1 forkhead transcription factor is targeted by recurrent chromosome translocations in several subtypes of B-cell non-Hodgkin lymphomas, where high-level FOXP1 protein expression has been linked to a poor prognosis. Western blotting studies of diffuse large B-cell lymphoma (DLBCL) cell lines unexpectedly identi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-09-115113

    authors: Brown PJ,Ashe SL,Leich E,Burek C,Barrans S,Fenton JA,Jack AS,Pulford K,Rosenwald A,Banham AH

    更新日期:2008-03-01 00:00:00

  • Glutathione S-transferase genotypes, genetic susceptibility, and outcome of therapy in childhood acute lymphoblastic leukemia.

    abstract::The glutathione S-transferase (GST) genes are involved in the metabolism of environmental carcinogens and of some classes of chemotherapy drugs. GSTM1 and GSTT1 genotypes are polymorphic in humans, and the phenotypic absence of enzyme activity is caused by a homozygous inherited deletion of the gene. Previous, smaller...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v100.1.67

    authors: Davies SM,Bhatia S,Ross JA,Kiffmeyer WR,Gaynon PS,Radloff GA,Robison LL,Perentesis JP

    更新日期:2002-07-01 00:00:00

  • Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT.

    abstract::Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of peripheral T-cell lymphomas with a poor prognosis. Autologous stem cell transplantation (ASCT) was retrospectively evaluated as a consolidation or salvage strategy for EATL. The analysis included 44 patients who received ASCT for EATL between 2000 and ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-11-466839

    authors: Jantunen E,Boumendil A,Finel H,Luan JJ,Johnson P,Rambaldi A,Haynes A,Duchosal MA,Bethge W,Biron P,Carlson K,Craddock C,Rudin C,Finke J,Salles G,Kroschinsky F,Sureda A,Dreger P,Lymphoma Working Party of the EBMT.

    更新日期:2013-03-28 00:00:00

  • Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.

    abstract::The molecular basis of different outcomes in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionizing radiation (IR)-induced DNA double-strand breaks in 74 pediatric patients with ALL. We found an apopto...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-03-142950

    authors: Marston E,Weston V,Jesson J,Maina E,McConville C,Agathanggelou A,Skowronska A,Mapp K,Sameith K,Powell JE,Lawson S,Kearns P,Falciani F,Taylor M,Stankovic T

    更新日期:2009-01-01 00:00:00

  • Variable heavy chain gene analysis of follicular lymphomas: correlation between heavy chain isotype expression and somatic mutation load.

    abstract::The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between so...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Aarts WM,Bende RJ,Steenbergen EJ,Kluin PM,Ooms EC,Pals ST,van Noesel CJ

    更新日期:2000-05-01 00:00:00

  • Serial studies in von Willebrand's disease: variability versus "variants".

    abstract::The variability of laboratory findings in von Willebrand's disease (vWd) was evaluated by performing serial studies of bleeding time (BT), factor VIII coagulant activity (VIII:C), factor-VIII-related antigen (VIIIR:Ag) and ristocetin cofactor (VIIIR:Rcof) in 50 individuals from 25 families with this disorder. The type...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Abildgaard CF,Suzuki Z,Harrison J,Jefcoat K,Zimmerman TS

    更新日期:1980-10-01 00:00:00

  • Correlation of minor histocompatibility antigen-specific cytotoxic T lymphocytes with graft-versus-host disease status and analyses of tissue distribution of their target antigens.

    abstract::Peripheral blood mononuclear cells (PBMC) from 17 patients receiving HLA-identical sibling bone marrow grafts were stimulated with host pretransplant PBMC. Cytotoxic T-cell lines (TCL) with specificity for host pretransplant PBMC were obtained from 9 of these patients, all presenting with severe graft-versus-host dise...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Niederwieser D,Grassegger A,Auböck J,Herold M,Nachbaur D,Rosenmayr A,Gächter A,Nussbaumer W,Gaggl S,Ritter M

    更新日期:1993-04-15 00:00:00

  • Distinct classes of c-Kit-activating mutations differ in their ability to promote RUNX1-ETO-associated acute myeloid leukemia.

    abstract::The t(8;21) RUNX1-ETO translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukemia (AML). In RUNX1-ETO(+) patient samples, differing classes of activating c-KIT receptor tyrosine kinase mutations have been observed. The most common (12%-48%) involves mutations, such as D816V, which occ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-02-338228

    authors: Nick HJ,Kim HG,Chang CW,Harris KW,Reddy V,Klug CA

    更新日期:2012-02-09 00:00:00

  • Identification and characterization of epitopes of the receptor for hyaluronic acid-mediated motility (RHAMM/CD168) recognized by CD8+ T cells of HLA-A2-positive patients with acute myeloid leukemia.

    abstract::The receptor for hyaluronic acid-mediated motility (RHAMM/CD168) has been described as a leukemia-associated antigen. To define T-cell epitopes of RHAMM/CD168 toward specific immunotherapies for acute myeloid leukemia (AML), 10 potential HLA-A2-binding RHAMM/CD168 peptides (R1 to R10) were synthesized based on compute...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-12-4787

    authors: Greiner J,Li L,Ringhoffer M,Barth TF,Giannopoulos K,Guillaume P,Ritter G,Wiesneth M,Döhner H,Schmitt M

    更新日期:2005-08-01 00:00:00

  • How I treat MDS and AML in Fanconi anemia.

    abstract::Fanconi anemia (FA) is the most frequent inherited cause of bone marrow failure (BMF). Most FA patients experience hematopoietic stem cell attrition and cytopenia during childhood, which along with intrinsic chromosomal instability, favor clonal evolution and the frequent emergence in their teens or young adulthood of...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-01-583625

    authors: Peffault de Latour R,Soulier J

    更新日期:2016-06-16 00:00:00

  • A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype.

    abstract::The Duffy blood group system is of clinical and biological significance. Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease. The Duffy protein is a receptor for the Plasmodium vivax erythrocyte-binding protein and is also a receptor for various chem...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Parasol N,Reid M,Rios M,Castilho L,Harari I,Kosower NS

    更新日期:1998-10-01 00:00:00

  • Gene therapy, an ongoing revolution.

    abstract::In this issue of Blood, Buchlis and colleagues describe the long-term persistence (up to 10 years) of factor IX (FIX) expression in adeno-associated virus serotype 2 (AAV-2)–injected muscles of a patient with hemophilia B. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2012-02-409086

    authors: Benveniste O

    更新日期:2012-03-29 00:00:00

  • Enrichment of functional CD8 memory T cells specific for MUC1 in bone marrow of patients with multiple myeloma.

    abstract::Multiple myeloma (MM) is one of the most common hematologic malignancies. Despite extensive therapeutical approaches, cures remain rare exceptions. An important issue for future immunologic treatments is the characterization of appropriate tumor-associated antigens. Recently, a highly glycosylated mucin MUC1 was detec...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-01-0366

    authors: Choi C,Witzens M,Bucur M,Feuerer M,Sommerfeldt N,Trojan A,Ho A,Schirrmacher V,Goldschmidt H,Beckhove P

    更新日期:2005-03-01 00:00:00