Abstract:
:Filamin A (FLNa), a dimeric actin cross-linking and scaffold protein with numerous intracellular binding partners, anchors the platelet adhesion glycoprotein (GP) Ib-IX-V receptor to actin cytoskeleton. We mapped the GPIbalpha binding site to a single domain of FLNa and resolved the structure of this domain and its interaction complex with the corresponding GPIbalpha cytoplasmic domain. This is the first atomic structure of this class of membrane glycoprotein-cytoskeleton connection. GPIbalpha binds in a groove formed between the C and D beta strands of FLNa domain 17. The interaction is strikingly similar to that between the beta7 integrin tail and a different FLNa domain, potentially defining a conserved motif for FLNa binding. Nevertheless, the structures also reveal specificity of the interfaces, which explains different regulatory mechanisms. To verify the topology of GPIb-FLNa interaction we also purified the native complex from platelets and showed that GPIb interacts with the C-terminus of FLNa, which is in accordance with our biochemical and structural data.
journal_name
Bloodjournal_title
Bloodauthors
Nakamura F,Pudas R,Heikkinen O,Permi P,Kilpeläinen I,Munday AD,Hartwig JH,Stossel TP,Ylänne Jdoi
10.1182/blood-2005-10-3964subject
Has Abstractpub_date
2006-03-01 00:00:00pages
1925-32issue
5eissn
0006-4971issn
1528-0020pii
2005-10-3964journal_volume
107pub_type
杂志文章相关文献
BLOOD文献大全abstract::The PI3K/Akt/mTOR pathway has emerged as a critical regulator of dendritic cell (DC) development and function. The kinase mTOR is found in 2 distinct complexes, mTORC1 and mTORC2. In this study, we show that mTORC1 but not mTORC2 is required for epidermal Langerhans cell (LC) homeostasis. Although the initial seeding ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-439786
更新日期:2013-01-10 00:00:00
abstract::The erythroblastic island (EI), formed by a central macrophage and developing erythroblasts (EBs), was first described decades ago and was recently shown to play an in vivo role in homeostatic and pathological erythropoiesis. The exact molecular mechanisms, however, mediating the interactions between macrophages and E...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2018-11-888180
更新日期:2019-03-14 00:00:00
abstract::The transforming growth factor-beta (TGF-beta) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia (1% O(2)) increases gene expression and bioactivation of TGF-beta2 and induces its downstream ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-02-0629
更新日期:2003-03-15 00:00:00
abstract::Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in normal and sublethally irradiated mice, dogs, and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carcinoma. IL-6 was administered during an ...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1995-05-01 00:00:00
abstract::In common variable immunodeficiency (CVID) defects in early stages of B-cell development, bone marrow (BM) plasma cells and T lymphocytes have not been studied systematically. Here we report the first morphologic and flow cytometric study of B- and T-cell populations in CVID BM biopsies and aspirates. Whereas the hema...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-321695
更新日期:2011-07-14 00:00:00
abstract::Natural killer (NK) cells participate in host defense by surveying for and ultimately killing virally infected or malignant target cells. NK cell cytotoxicity is a tightly regulated process that proceeds stepwise from adhesion and activation to the secretion of preformed lytic granule contents onto a diseased or stres...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-06-437012
更新日期:2013-04-04 00:00:00
abstract::The t(11;14)(q13;q32) is the most common translocation in multiple myeloma (MM), resulting in up-regulation of cyclin D1. We used a segregation fluorescence in situ hybridization (FISH) assay to detect t(11;14) breakpoints in primary MM cases and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to qu...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-11-3837
更新日期:2004-08-15 00:00:00
abstract::C-abl oncogene 1, nonreceptor tyrosine kinase (ABL1) kinase inhibitors such as imatinib mesylate (imatinib) are effective in managing chronic myeloid leukemia (CML) but incapable of eliminating leukemia stem cells (LSCs), suggesting that kinase-independent pathways support LSC survival. Given that the bone marrow (BM)...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-07-511907
更新日期:2014-05-22 00:00:00
abstract::Thymus atrophy is the most common immunopathology in humans, and its occurrence is hastened by several factors that coalesce in patients receiving chemotherapy and most of all in recipients of hematopoietic cell transplantation. We have shown previously that posthematopoietic cell transplantation thymic function was i...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-04-350553
更新日期:2011-11-10 00:00:00
abstract::In subjects mismatched in the HLA alleles C*03:03/C*03:04 no allogeneic cytotoxic T-lymphocyte responses are detected in vitro. Hematopoietic stem cell transplantation (HSCT) with unrelated donors (UDs) showed no association between the HLA-C allele mismatches (CAMMs) and adverse outcomes; antigen mismatches at this a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-10-532671
更新日期:2014-02-20 00:00:00
abstract::P-selectin glycoprotein ligand-1 (PSGL-1) serves as the leukocyte ligand for P-selectin, and many of the structural features of its ectodomain required for interactions with P-selectin have been uncovered. In contrast, the function of the highly conserved PSGL-1 cytoplasmic domain has not been explored. Stable transfe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.12.4494
更新日期:2002-06-15 00:00:00
abstract::The tetraspanin family member CD151 forms complexes with integrins and regulates cell adhesion and migration. While CD151 is highly expressed in megakaryocytes and to a lesser extent in platelets, its physiologic role in platelets is unclear. In this study, we investigate the physical and functional importance of CD15...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-12-4430
更新日期:2004-10-15 00:00:00
abstract::Malignant transformation by oncogenes requires additional genetic/epigenetic changes to overcome enhanced susceptibility to apoptosis. In the present study, we report that Bif-1 (Sh3glb1), a gene encoding a membrane curvature–driving endophilin protein, is a haploinsufficient tumor suppressor that plays a key role in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-10-459826
更新日期:2013-02-28 00:00:00
abstract::Primary effusion lymphoma (PEL) is an aggressive HIV-associated lymphoma with a relatively poor prognosis in the era of effective HIV therapy. Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent, and ∼80% of tumors are coinfected with Epstein-Barr virus (EBV). A better understanding of how KSHV-related immune dys...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2019-01-893339
更新日期:2019-04-18 00:00:00
abstract::Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease defined by transcriptional classifications, specific signaling and survival pathways, and multiple low-frequency genetic alterations. Preclinical model systems that capture the genetic and functional heterogeneity of DLBCL are urgently needed. Here, we g...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-09-672352
更新日期:2016-05-05 00:00:00
abstract::We developed a risk score to predict event-free survival (EFS) after allogeneic hematopoietic cell transplantation for sickle cell disease. The study population (n = 1425) was randomly split into training (n = 1070) and validation (n = 355) cohorts. Risk factors were identified and validated via Cox regression models....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005687
更新日期:2020-07-30 00:00:00
abstract::Angiotensin I-converting enzyme (ACE) inhibitors can affect hematopoiesis by several mechanisms including inhibition of angiotensin II formation and increasing plasma concentrations of AcSDKP (acetyl-N-Ser-Asp-Lys-Pro), an ACE substrate and a negative regulator of hematopoiesis. We tested whether ACE inhibition could ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-11-3828
更新日期:2004-08-15 00:00:00
abstract::Using quantitative fluorescence in situ hybridization and flow cytometry, the telomere length of telomere repeat sequences after stem cell transplantation (SCT) were measured. The study included the telomeres of peripheral blood monocytes that should reflect the length of telomeres in stem cells and the telomeres of T...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v97.2.575
更新日期:2001-01-15 00:00:00
abstract::Expression of inhibitory killer cell immunoglobulin-like receptors (KIRs) specific for self-major histocompatibility complex (MHC) class I molecules provides an educational signal that generates functional natural killer (NK) cells. However, the effects of activating KIRs specific for self-MHC class I on NK-cell educa...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-09-245746
更新日期:2010-02-11 00:00:00
abstract::Tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 are proteins with proteinase-inhibiting and cytokine properties. TIMP-1 is active primarily in B cells and B-cell lymphomas, whereas TIMP-2 expression is restricted to T cells. The expression of TIMP-1 and TIMP-2 in lymph nodes from patients with Hodgkin disea...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.1.258
更新日期:2002-01-01 00:00:00
abstract::Von Willebrand disease (VWD)-type 2B originates from a gain-of-function mutation in von Willebrand factor (VWF), resulting in enhanced platelet binding. Clinical manifestations include increased bleeding tendency, loss of large multimers, thrombocytopenia, and circulating platelet aggregates. We developed a mouse mode...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-11-254193
更新日期:2010-06-10 00:00:00
abstract::The p21-activated kinases (Paks) are serine/threonine kinases that are major effectors of the Rho guanosine 5'\x{2011}triphosphatase, Rac, and Cdc42. Rac and Cdc42 are known regulators of hematopoietic stem and progenitor cell (HSPC) function, however, a direct role for Paks in HSPCs has yet to be elucidated. Lin(-)Sc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-10-460709
更新日期:2013-03-28 00:00:00
abstract::Using highly sensitive 2-site immunoradiometric assays, we examined the relationship between iron absorption from closed intestinal loops and transferrin and ferritin concentrations in isolated duodenal mucosal cells. As in prior studies, mucosal ferritin correlates inversely with iron absorption and directly with bod...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of myeloid neoplasms with eosinophilia. The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, "Myeloid/lymphoid neoplasms with eosinophil...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-10-695973
更新日期:2017-02-09 00:00:00
abstract::Chronic active EBV disease (CAEBV) is a lymphoproliferative disorder characterized by markedly elevated levels of antibody to EBV or EBV DNA in the blood and EBV RNA or protein in lymphocytes in tissues. We present our experience with CAEBV during the last 28 years, including the first 8 cases treated with hematopoiet...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-316745
更新日期:2011-06-02 00:00:00
abstract::The Leukemia and Lymphoma Molecular Profiling Project recently published results from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four gene expression "signatures" were identified as correlated with patient outcome, including the major histocompatibility complex (MHC) class II genes (eg, HL...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-07-2365
更新日期:2004-06-01 00:00:00
abstract::Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell-mediated diseases. As a part of a phase 1, multicenter, dose-escalating trial of humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), the autoimmune response to gl...
journal_title:Blood
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1182/blood-2003-06-2167
更新日期:2004-02-15 00:00:00
abstract::In this issue of Blood, Bartel and colleagues report the independent predictive value of the PET/CT and of the FDG suppression before transplantation in newly diagnosed myeloma patients who were treated using the TT3 regimen. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2009-06-224196
更新日期:2009-09-03 00:00:00
abstract::Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)--fractionated human cord blood cells were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice. High levels of multilineage engraftment, including myeloid and lymphoid lineages, were obtained with 80% of the donor samples as asse...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::This article reports a Glanzmann thrombasthenia (GT) patient, N.M., with a point mutation in the third cysteine-rich repeat of beta3-integrin or platelet glycoprotein (GP) IIIa, leading to the expression of a constitutively activated fibrinogen receptor. The diagnosis of GT was based on a severely reduced platelet-agg...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.8.2432
更新日期:2001-10-15 00:00:00