Abstract:
:Erythropoietin (EPO) is required for the survival and expansion of red blood cell progenitor cells and supports continued differentiation of these committed progenitors to mature red blood cells. After binding to its cognate receptor, EPO promotes receptor homodimerization, activation of receptor-associated JAK2, subsequent receptor tyrosine phosphorylation, and transduction of signal. EPO is also internalized and degraded in lysosomes. The contribution of EPO-induced receptor internalization to modulation of EPO signals has not been determined. To examine this question, we generated a panel of hematopoietic cell lines containing progressively truncated isoforms of the erythropoietin receptor (EPO-R) and determined the rate and extent of EPO internalization and receptor downregulation. We demonstrated that a membrane-proximal domain of the cytoplasmic tail of the EPO-R was the minimal region required for EPO-induced receptor internalization. This cytoplasmic domain is also the minimal domain required for activation of JAK2, a cytosolic tyrosine kinase essential for the function of the EPO-R. However, neither EPO activation of cytosolic JAK2 tyrosine kinase activity nor tyrosine phosphorylation of the EPO-R cytoplasmic tail was required for EPO-induced receptor downregulation. Both functional and nonfunctional cell surface receptor isoforms were internalized equally. These results suggest that, for downregulation of cell surface ligand occupied EPO-R and possibly for signaling receptors of the cytokine receptor superfamily in general, internalization of cell surface ligand occupied receptors may follow a pathway distinct from signaling receptors of the receptor tyrosine kinase (RTK) family.
journal_name
Bloodjournal_title
Bloodauthors
Beckman DL,Lin LL,Quinones ME,Longmore GDsubject
Has Abstractpub_date
1999-10-15 00:00:00pages
2667-75issue
8eissn
0006-4971issn
1528-0020journal_volume
94pub_type
杂志文章相关文献
BLOOD文献大全abstract::Previous studies on patients with storage pool deficiency (SPD) who are specifically deficient in platelet dense granules (delta-SPD) have suggested a role for dense granule substances, in all likelihood adenosine diphosphate (ADP), in mediating thrombus formation on subendothelium at high shear rates. The role of den...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-05-15 00:00:00
abstract::STI571 induces sustained hematologic remission in patients with chronic myeloid leukemia (CML) in chronic phase. However, in advanced phases, especially blast crisis, the leukemia usually becomes resistant within months. It has been investigated whether resistance to STI571 is stable and immutable or whether it can be...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.13.3864
更新日期:2001-12-15 00:00:00
abstract::The study of central nervous system (CNS) leukemia has been hampered by the lack of a suitable animal model. We report that severe combined immunodeficiency (SCID) mice invariably develop rapidly progressive fatal CNS leukemia within 3 weeks after intravenous injection of NALM-6 pre-B acute lymphoblastic leukemia (ALL...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-05-01 00:00:00
abstract::To evaluate the association between fetal hemoglobin (HbF) levels and morbidity in β-thalassemia intermedia (TI), we analyzed data from 63 untransfused patients who had also never received HbF induction therapy. Patient records were reviewed for any history of 10 predefined morbidities. Laboratory measurements for mar...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2011-09-382408
更新日期:2012-01-12 00:00:00
abstract::We analyzed the expression of myelomonocytic-associated antigens on lymphocytes from B cell chronic lymphocytic leukemia (B-CLL) patients. Blood mononuclear cells were depleted of monocytes by one-step Percoll density gradient centrifugation and tested for antigen expression by fluorescent microscopy and flow cytometr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Factor XIII is the fibrin-stabilizing factor that covalently cross-links fibrin monomers to form a highly organized, stable fibrin clot. The plasma form of factor XIII is a heterodimer, a2b2, consisting of two a-chains and two b-chains; the intracellular form, such as in platelets and placenta, is a dimer, a2, consist...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::Measurements of hepatic iron concentration (HIC) are important predictors of transfusional iron burden and long-term outcome in patients with transfusion-dependent anemias. The goal of this work was to develop a readily available, noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2) and R2* ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-10-3982
更新日期:2005-08-15 00:00:00
abstract::We used a sensitive, quantitative bisulfite PCR assay, methylation sensitive single nucleotide primer extension (Ms-SNuPE), to measure methylation of the 5' CpG islands of c-abl and p15 in chronic myelogenous leukemia (CML) patients during progression. We found that the Pa promoter of c-abl was methylated in 81% (17/2...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
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
更新日期:2011-09-22 00:00:00
abstract::Between February 1996 and December 2004, the German Leukemia Study Initiative registered 1766 consecutive patients for the acute myeloid leukemia (AML) 96 study, all of whom were diagnosed by central cytomorphology according to the French-American-British (FAB) and the new World Health Organization (WHO) classificatio...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2007-08-101162
更新日期:2008-02-15 00:00:00
abstract::Drug-induced immune thrombocytopenia (DITP) is caused by antibodies that react with specific platelet-membrane glycoproteins when the provoking drug is present. More than 100 drugs have been implicated as triggers for this condition, quinine being one of the most common. The cause of DITP in most cases appears to be a...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-04-639351
更新日期:2015-10-29 00:00:00
abstract::We have identified and cloned a novel human cytokine with homology to cytokines of the interleukin-17 (IL-17) family, which we have termed human IL-17E (hIL-17E). With the identification of several IL-17 family members, it is critical to understand the in vivo function of these molecules. We have generated transgenic ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-01-0012
更新日期:2002-10-01 00:00:00
abstract::Anaplastic large cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive anaplastic lymphoma kinase (ALK) fusion protein. ALK inhibitors, such as crizotinib, provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by nucleophosmin 1...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019003793
更新日期:2020-10-01 00:00:00
abstract::Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Autologous stem cell transplantation (ASCT) is considered the gold standard in the frontline therapy of younger patients with multiple myeloma because it results in higher complete remission (CR) rates and longer event-free survival than conventional chemotherapy. The greatest benefit from ASCT is obtained in patients...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2009-08-238196
更新日期:2010-05-06 00:00:00
abstract::Homing of blood-borne lymphocytes to peripheral lymph nodes (PLNs) is a multistep process dependent on the sequential engagement of L-selectin, which mediates lymphocyte rolling along the luminal surface of high endothelial venules (HEVs), followed by activation of lymphocyte integrins and transmigration through HEVs....
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-03-0841
更新日期:2003-01-01 00:00:00
abstract::Understanding the molecular pathogenesis of lymphoma has led to paradigm-changing treatment opportunities. One example involves tailoring specific agents based on the cell of origin in aggressive lymphomas. Germinal center (GC)-derived diffuse large B-cell lymphoma (DLBCL) is known to be driven by an addiction to Bcl6...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-02-485441
更新日期:2013-09-19 00:00:00
abstract::Pediatric arterial ischemic stroke (AIS) is increasingly diagnosed and carries significant risks of recurrence, morbidity, and mortality. Anticoagulant therapy (ACT) is commonly prescribed in childhood AIS. Hemorrhagic complication rates in pediatric stroke are unknown, and adult safety data are of limited applicabili...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-06-361535
更新日期:2012-01-26 00:00:00
abstract::High-molecular weight DNAs of fresh bone marrow cells from 32 patients with fresh leukemia were assayed for the presence of transmissible activated transforming genes by a DNA-mediated gene transfer technique using NIH/3T3 cells. DNAs of bone marrow cells from four of the 32 patients induced transformation of NIH/3T3 ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::Healthy blood neutrophils are functionally quiescent in the bloodstream, have a short lifespan, and exit the circulation to carry out innate immune functions, or undergo rapid apoptosis and macrophage-mediated clearance to mitigate host tissue damage. Limitation of unnecessary intravascular neutrophil activation is al...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-11-751636
更新日期:2017-06-08 00:00:00
abstract::Bcr-abl fusion peptide-specific CD4+ T-lymphocyte clones have recently been shown to augment colony formation by chronic myelogenous leukemia (CML) cells in a bcr-abl type-specific and HLA class II-restricted manner without addition of exogenous antigen. These findings suggest that CML cells can naturally process and ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.5.1498
更新日期:2001-09-01 00:00:00
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:
更新日期:2000-01-01 00:00:00
abstract::Erdheim-Chester disease (ECD) pathophysiology remains largely unknown. Its treatment is not codified and usually disappointing. Interferon (IFN)-α therapy lacks efficacy for some life-threatening manifestations and has a poor tolerance profile. Because interleukin (IL)-1Ra synthesis is naturally induced after stimulat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-279240
更新日期:2010-11-18 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::Fanconi anemia (FA) is an autosomal recessive syndrome characterized by progressive bone marrow failure and cancer predisposition. Eight FA complementation groups have been identified. The FANCA, FANCC, FANCE, FANCF, and FANCG proteins form a nuclear complex required for the monoubiquination of the FANCD2 protein. To ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-11-3517
更新日期:2003-07-01 00:00:00
abstract::Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and its human homologue GOS19.1/LD78 are members of the C-C chemokine/intercrine family of secreted proteins. They have proinflammatory properties and also inhibit cell cycle progression of hematopoietic stem cells. Characterization of MIP-1 alpha receptor(s) has b...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-09-15 00:00:00
abstract::Allogeneic hematopoietic stem cell transplantation (HSCT) is widely used to treat hematopoietic cell disorders but is often complicated by graft-versus-host disease (GVHD), which causes severe epithelial damage. Here we have investigated longitudinally the effects of induction chemotherapy, conditioning radiochemother...
journal_title:Blood
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1182/blood-2013-11-536888
更新日期:2014-07-31 00:00:00
abstract::CD44 is a widely expressed, multifunctional, cell-surface glycoprotein that has been implicated in the regulation of normal hematopoiesis. In addition, expression of particular isoforms of CD44 has been associated with malignant transformation and/or the acquisition of metastatic potential. In this study, we used two ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-10-15 00:00:00
abstract::As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known cli...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-01-261396
更新日期:2010-06-10 00:00:00
abstract::To define the role of the alpha2beta1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and alpha2-null mice. Our findings reveal that the alpha2beta1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-06-094680
更新日期:2008-02-15 00:00:00