A unique interaction between alphaIIb and beta3 in the head region is essential for outside-in signaling-related functions of alphaIIbbeta3 integrin.

Abstract:

:The main interface of the 2 subunits of platelet integrin alphaIIbbeta3 comprises the beta-propeller domain of alphaIIb and the betaA domain of beta3. In the center of the beta-propeller, several aromatic residues interact by cation-pi and hydrophobic bonds with Arg261 of betaA. In this study, we substituted alphaIIb-Trp110 or beta3-Arg261 by residues abundant in other alpha or beta subunits at corresponding locations and expressed them in baby hamster kidney cells along with normal beta3 or alphaIIb, respectively. These mutant cells displayed normal surface expression and fibrinogen binding but grossly impaired outside-in signaling-related functions: adhesion to immobilized fibrinogen, cell spreading, focal adhesion kinase phosphorylation, clot retraction, and reduced alphaIIbbeta3 stability in EDTA (ethylenediaminetetraacetic acid). Expression of mutants with substitutions of Arg261 in beta3 by alanine or lysine with normal alphav yielded normal surface expression of alphavbeta3 and soluble fibrinogen binding as well as normal outside-in signaling-related functions, contrasting findings for alphaIIbbeta3. Structural analysis of alphaIIbbeta3 and alphavbeta3 revealed that alphavbeta3 has several strong interactions between alphav and beta3 subunits that are missing in alphaIIbbeta3. Together, these findings indicate that the interaction between Trp110 of alphaIIb and Arg261 of beta3 is critical for alphaIIbbeta3 integrity and outside-in signaling-related functions.

journal_name

Blood

journal_title

Blood

authors

Hauschner H,Landau M,Seligsohn U,Rosenberg N

doi

10.1182/blood-2009-10-251066

subject

Has Abstract

pub_date

2010-06-03 00:00:00

pages

4542-50

issue

22

eissn

0006-4971

issn

1528-0020

pii

blood-2009-10-251066

journal_volume

115

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Altered NKG2D function in NK cells induced by chronic exposure to NKG2D ligand-expressing tumor cells.

    abstract::NKG2D is an activation receptor that allows natural killer (NK) cells to detect diseased host cells. The engagement of NKG2D with corresponding ligand results in surface modulation of the receptor and reduced function upon subsequent receptor engagement. However, it is not clear whether in addition to modulation the N...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-03-0918

    authors: Coudert JD,Zimmer J,Tomasello E,Cebecauer M,Colonna M,Vivier E,Held W

    更新日期:2005-09-01 00:00:00

  • Use of limiting-dilution type long-term marrow cultures in frequency analysis of marrow-repopulating and spleen colony-forming hematopoietic stem cells in the mouse.

    abstract::We have developed an in vitro clonal assay of murine hematopoietic precursor cells that form spleen colonies (CFU-S day 12) or produce in vitro clonable progenitors in the marrow (MRA cells) of lethally irradiated mice. The assay is essentially a long-term bone marrow culture in microtiter wells containing marrow-deri...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Ploemacher RE,van der Sluijs JP,van Beurden CA,Baert MR,Chan PL

    更新日期:1991-11-15 00:00:00

  • Phenotype analysis of hematopoietic CD34+ cell populations derived from human umbilical cord blood using flow cytometry and cDNA-polymerase chain reaction.

    abstract::A strategy to phenotype rare populations of hematopoietic cells expressing the cell-surface marker CD34 was studied. The antigenic phenotype of umbilical core blood (CB) CD34+ cells was investigated using flow cytometry and compared with the mRNA-phenotype determined by cDNA-polymerase chain reaction (cDNA-PCR) analys...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Thoma SJ,Lamping CP,Ziegler BL

    更新日期:1994-04-15 00:00:00

  • Ontogeny of CD4+CD25+ regulatory/suppressor T cells in human fetuses.

    abstract::Little is known about the ontogeny of naturally occurring CD4(+)CD25(+) regulatory/suppressor T cells that play a major role in maintaining self-tolerance in mice and humans. In rodents, thymectomy on day 3 of life leads to multiple organ-specific autoimmune diseases that can be prevented by adoptive transfer of regul...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-10-4051

    authors: Darrasse-Jèze G,Marodon G,Salomon BL,Catala M,Klatzmann D

    更新日期:2005-06-15 00:00:00

  • In situ immunologic characterization of cellular constituents in lymph nodes and spleens involved by Hodgkin's disease.

    abstract::The cellular constituents in lymph nodes and spleens of patients with Hodgkin's disease were studied with a series of monoclonal antibodies directed against human thymocyte, peripheral T-cell, and la antigens. Utilizing both an immunoperoxidase technique on frozen tissue sections and indirect immunofluorescence on cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Poppema S,Bhan AK,Reinherz EL,Posner MR,Schlossman SF

    更新日期:1982-02-01 00:00:00

  • Growth of clonogenic myeloblastic leukemic cells in the presence of human recombinant erythropoietin in addition to various human recombinant hematopoietic growth factors.

    abstract::The effects of human recombinant erythropoietin (rEpo) in the presence of other stimulators on the growth of clonogenic leukemic blast cells from ten Japanese patients with acute myeloblastic leukemia were studied with an in vitro leukemic blast colony assay in methylcellulose culture. With the addition of rEpo alone,...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Asano Y,Okamura S,Shibuya T,Harada M,Niho Y

    更新日期:1988-11-01 00:00:00

  • Altered factor VII activity in hemophilia.

    abstract::Factor VII levels have been studied in hemophilia A and B plasmas and normal controls in a controlled, prospective study. Three assay methods were used: a standard clotting assay (FVIIc-A); a modified clotting assay (FVIIc-B) (Seligsohn et al, Blood 52:978-988, 1978); and a coupled amidolytic assay. By the FVIIc-B ass...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miller BC,Hultin MB,Jesty J

    更新日期:1985-04-01 00:00:00

  • Δ12-prostaglandin J3, an omega-3 fatty acid-derived metabolite, selectively ablates leukemia stem cells in mice.

    abstract::Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ(12)-PGJ(3), a n...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-11-317750

    authors: Hegde S,Kaushal N,Ravindra KC,Chiaro C,Hafer KT,Gandhi UH,Thompson JT,van den Heuvel JP,Kennett MJ,Hankey P,Paulson RF,Prabhu KS

    更新日期:2011-12-22 00:00:00

  • Dexamethasone augments CXCR4-mediated signaling in resting human T cells via the activation of the Src kinase Lck.

    abstract::Dexamethasone (DM) is a synthetic member of the glucocorticoid (GC) class of hormones that possesses anti-inflammatory and immunosuppressant activity and is commonly used to treat chronic inflammatory disorders, severe allergies, and other disease states. Although GCs are known to mediate well-defined transcriptional ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-04-151803

    authors: Ghosh MC,Baatar D,Collins G,Carter A,Indig F,Biragyn A,Taub DD

    更新日期:2009-01-15 00:00:00

  • A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children.

    abstract::Important predictors of adverse outcomes of thrombosis in children, including postthrombotic syndrome (PTS), have recently been identified. Given this knowledge and the encouraging preliminary pediatric experience with systemic thrombolysis, we sought to retrospectively analyze our institutional experience with a thro...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-12-061234

    authors: Goldenberg NA,Durham JD,Knapp-Clevenger R,Manco-Johnson MJ

    更新日期:2007-07-01 00:00:00

  • Identification and characterization of osteoclast progenitors by clonal analysis of hematopoietic cells.

    abstract::We have identified a distinct population of colony-forming cells that give rise to mononuclear cells expressing an enzyme marker and other features of the osteoclast in bone marrow cultures stimulated by conditioned medium of a murine tumor cell line. These colony-forming cells were defined as osteoclast colony-formin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lee MY,Lottsfeldt JL,Fevold KL

    更新日期:1992-10-01 00:00:00

  • How I treat infant leukemia.

    abstract::Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its fascinating biology. Increasingly, these biological insights are pointing the way toward novel therapeutic approaches. Using represent...

    journal_title:Blood

    pub_type: 杂志文章,随机对照试验

    doi:10.1182/blood-2018-04-785980

    authors: Brown P,Pieters R,Biondi A

    更新日期:2019-01-17 00:00:00

  • Hepatitis C virus infection involves CD34(+) hematopoietic progenitor cells in hepatitis C virus chronic carriers.

    abstract::Although hepatitis C virus (HCV) mainly affects hepatocytes, infection is widespread and involves immunologically privileged sites. Whether lymphoid cells represent further targets of early HCV infection, or whether other cells in the hematopoietic microenvironment may serve as a potential virus reservoir, is still un...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sansonno D,Lotesoriere C,Cornacchiulo V,Fanelli M,Gatti P,Iodice G,Racanelli V,Dammacco F

    更新日期:1998-11-01 00:00:00

  • Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients.

    abstract::Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, ...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:

    authors: Niu C,Yan H,Yu T,Sun HP,Liu JX,Li XS,Wu W,Zhang FQ,Chen Y,Zhou L,Li JM,Zeng XY,Yang RR,Yuan MM,Ren MY,Gu FY,Cao Q,Gu BW,Su XY,Chen GQ,Xiong SM,Zhang TD,Waxman S,Wang ZY,Chen Z,Hu J,Shen ZX,Chen SJ

    更新日期:1999-11-15 00:00:00

  • The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model.

    abstract::Although NPM1 gene mutations leading to aberrant cytoplasmic expression of nucleophosmin (NPMc(+)) are the most frequent genetic lesions in acute myeloid leukemia, there is yet no experimental model demonstrating their oncogenicity in vivo. We report the generation and characterization of a transgenic mouse model expr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-03-208587

    authors: Cheng K,Sportoletti P,Ito K,Clohessy JG,Teruya-Feldstein J,Kutok JL,Pandolfi PP

    更新日期:2010-04-22 00:00:00

  • Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase.

    abstract::Despite the importance of phosphoinositide 3-kinase (PI3K) in B-cell development, its activation mechanism still remains elusive. In this study, we show that deletion of both BCAP and CD19 leads to an almost complete block of BCR-mediated Akt activation and to severe defects in generation of immature and mature B cell...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-08-109769

    authors: Aiba Y,Kameyama M,Yamazaki T,Tedder TF,Kurosaki T

    更新日期:2008-02-01 00:00:00

  • The role of the D1 domain of the von Willebrand factor propeptide in multimerization of VWF.

    abstract::While studying patient plasma containing an unusual pattern of von Willebrand factor (VWF) multimers, we discovered a previously unreported phenomenon: heavy predominance of dimeric VWF. Genomic analysis revealed a new congenital mutation (Tyr87Ser) that altered the final stages of VWF biosynthesis. This mutation in t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0789

    authors: Rosenberg JB,Haberichter SL,Jozwiak MA,Vokac EA,Kroner PA,Fahs SA,Kawai Y,Montgomery RR

    更新日期:2002-09-01 00:00:00

  • Discontinuation of fucose therapy in LADII causes rapid loss of selectin ligands and rise of leukocyte counts.

    abstract::Leukocyte adhesion deficiency type II (LADII) is a rare inherited disorder of fucose metabolism. Patients with LADII lack fucosylated glycoconjugates, including the carbohydrate ligands of the selectins, leading to an immunodeficiency caused by the lack of selectin-mediated leukocyte-endothelial interactions. A simple...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.1.330

    authors: Lühn K,Marquardt T,Harms E,Vestweber D

    更新日期:2001-01-01 00:00:00

  • Structural and functional characterization of a specific antidote for ticagrelor.

    abstract::Ticagrelor is a direct-acting reversibly binding P2Y12 antagonist and is widely used as an antiplatelet therapy for the prevention of cardiovascular events in acute coronary syndrome patients. However, antiplatelet therapy can be associated with an increased risk of bleeding. Here, we present data on the identificatio...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-01-622928

    authors: Buchanan A,Newton P,Pehrsson S,Inghardt T,Antonsson T,Svensson P,Sjögren T,Öster L,Janefeldt A,Sandinge AS,Keyes F,Austin M,Spooner J,Gennemark P,Penney M,Howells G,Vaughan T,Nylander S

    更新日期:2015-05-28 00:00:00

  • Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial.

    abstract::Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patie...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2020005288

    authors: Voorhees PM,Kaufman JL,Laubach J,Sborov DW,Reeves B,Rodriguez C,Chari A,Silbermann R,Costa LJ,Anderson LD Jr,Nathwani N,Shah N,Efebera YA,Holstein SA,Costello C,Jakubowiak A,Wildes TM,Orlowski RZ,Shain KH,Cowan AJ,

    更新日期:2020-08-20 00:00:00

  • Vav proteins regulate peripheral B-cell survival.

    abstract::Mice lacking all 3 Vav proteins fail to produce significant numbers of recirculating follicular or marginal zone B cells. Those B cells that do mature have shortened lifespans. The constitutive nuclear factor-kappaB (NF-kappaB) activity of resting naive B cells required Vav function and expression of cellular reticulo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-12-4894

    authors: Vigorito E,Gambardella L,Colucci F,McAdam S,Turner M

    更新日期:2005-10-01 00:00:00

  • Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor.

    abstract::Monocytes from patients with sickle cell disease (SCD) are in an activated state. However, the mechanism of activation of monocytes in SCD is not known. Our studies showed that placenta growth factor (PlGF) activated monocytes and increased mRNA levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-11-3423

    authors: Selvaraj SK,Giri RK,Perelman N,Johnson C,Malik P,Kalra VK

    更新日期:2003-08-15 00:00:00

  • Changing antigen receptor gene rearrangements in a case of early pre-B cell leukemia: evidence for a tumor progenitor cell with stem cell features and implications for monitoring residual disease.

    abstract::A case of acute lymphoblastic leukemia (ALL) was encountered in which the two clonal gamma T-cell receptor gene (TCR gamma) rearrangements found in bone marrow (BM) samples at relapse both differed from the single clonal TCR gamma rearrangement present in BM obtained at diagnosis 5 years previously. In contrast, two c...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tycko B,Ritz J,Sallan S,Sklar J

    更新日期:1992-01-15 00:00:00

  • Microsatellite instability and p53 mutations are associated with abnormal expression of the MSH2 gene in adult acute leukemia.

    abstract::Microsatellite instability (MSI) and p53 mutations have been reported to occur in a significant proportion of patients with therapy-related acute myeloid leukemia (AML). MSH2 is one of the genes involved in DNA mismatch repair to maintain fidelity of genomic replication, and defects of MSH2 are directly involved in MS...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Zhu YM,Das-Gupta EP,Russell NH

    更新日期:1999-07-15 00:00:00

  • Cytogenetic evolution patterns in non-Hodgkin's lymphoma.

    abstract::Secondary chromosomal aberrations were surveyed in non-Hodgkin's lymphomas (NHL) reported in the literature with one of the following, presently recognized, primary abnormalities: t(2;5), +3, t(3;14), del(6q), +X, and -Y. Of 2,175 NHLs with clonal karyotypic changes, 908 (42%) had one of the 13 selected primary chromo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Johansson B,Mertens F,Mitelman F

    更新日期:1995-11-15 00:00:00

  • Thyroid hormone regulates hematopoiesis via the TR-KLF9 axis.

    abstract::Congenital hypothyroidism (CH) is one of the most prevalent endocrine diseases, for which the underlying mechanisms remain unknown; it is often accompanied by anemia and immunodeficiency in patients. Here, we created a severe CH model together with anemia and T lymphopenia to mimic the clinical features of hypothyroid...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-05-783043

    authors: Zhang Y,Xue Y,Cao C,Huang J,Hong Q,Hai T,Jia Q,Wang X,Qin G,Yao J,Wang X,Zheng Q,Zhang R,Li Y,Luo A,Zhang N,Shi G,Wang Y,Ying H,Liu Z,Wang H,Meng A,Zhou Q,Wei H,Liu F,Zhao J

    更新日期:2017-11-16 00:00:00

  • To be, or not to be, an eosinophil: that is the ???

    abstract::In this issue of Blood, Doyle et al provide evidence that knockout of the genes encoding the two most abundant eosinophil secondary granule proteins disrupts the normal differentiation of eosinophils from progenitors in the bone marrow, providing a novel strain of mice with a highly specific deficiency in eosinophilop...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2013-06-508507

    authors: Ackerman SJ

    更新日期:2013-08-01 00:00:00

  • Mutations of the N-ras gene in juvenile chronic myelogenous leukemia.

    abstract::Juvenile chronic myelogenous leukemia (JCML), a myeloproliferative disorder of childhood, is distinct from adult-type chronic myelogenous leukemia (CML) and bears resemblance to chronic myelomonocytic leukemia (CMMoL). Since mutations in the N-ras gene have been found at high frequencies in CMMoL, but only rarely in C...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Miyauchi J,Asada M,Sasaki M,Tsunematsu Y,Kojima S,Mizutani S

    更新日期:1994-04-15 00:00:00

  • Hematopoietic growth factor receptor genes as markers of lineage commitment during in vitro development of hematopoietic cells.

    abstract::We have used two in vitro models to identify genes whose expression may serve as markers of lineage commitment during the development of hematopoietic stem cells. One system involves the development in vitro of blastocyst-derived embryonic stem cells into embryoid bodies. The second involves culturing of day 3.5 blast...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McClanahan T,Dalrymple S,Barkett M,Lee F

    更新日期:1993-06-01 00:00:00

  • Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice.

    abstract::Recently, a novel gene of the major histocompatibility complex (MHC) class I family, HFE (HLA-H), has been found to be mutated in a large proportion of hereditary hemochromatosis (HH) patients. Further support for a causative role of HFE in this disease comes from the observation that beta2-microglobulin knockout (bet...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Santos M,Clevers H,de Sousa M,Marx JJ

    更新日期:1998-04-15 00:00:00