• IL-3 is a T cell-derived, pluripotent and hematopoietic factor required for survival and proliferation of hematopoietic progenitor cells. (wikipedia.org)
  • The signal transducer and activator of transcription 5 (STAT5) regulates differentiation, survival, proliferation and transformation of hematopoietic cells. (nature.com)
  • Expression of CBLDeltaexon8 and CBLDeltaexon8+9 in FLT3-WT-Ba/F3 cells induced growth factor-independent proliferation associated with autophosphorylation of FLT3 and activated the downstream targets signal transducer and activator of transcription 5 (STAT5) and protein kinase B (AKT). (jax.org)
  • Del exon8 results in ligand-independent Flt3 autophosphorylation, and activation of Stat5 and Akt, and leads to increased ligand-dependent proliferation, and IL-3 independent proliferation of cells in culture ( PMID: 19276253 ). (jax.org)
  • FLT3 ITD triggers the proliferation of the quiescent hematopoietic stem cell (HSC) pool but fails to directly transform HSCs. (biomedcentral.com)
  • BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. (oncotarget.com)
  • Subsequent results confirmed that RUNX1, as an independent prognostic factor for LGG, may target interferon-gamma receptor 2 (IFNGR2) to regulate glioma cell proliferation, invasion, and migration. (bjbms.org)
  • FGF-2 expands murine hematopoietic stem and progenitor cells via proliferation of stromal cells, c-Kit activation, and CXCL12 down-regulation. (mpg.de)
  • These factors stimulate proliferation, differentiation, and survival signals, as well as specialized functions in host resistance to pathogens. (sagepub.com)
  • Tyrosine 343 in the erythropoietin receptor positively regulates erythropoietin‐induced cell proliferation and Stat5 activation. (sagepub.com)
  • The type I IFN-induced CrkL pathway is critical for the proliferation of both hematopoietic and non-hematopoietic cells. (scientificarchives.com)
  • This study suggests that dihydrotanshinone I inhibits MV4-11 proliferation by apoptosis via antagonizing FLT3-ITD/STAT5/Mcl-1 path-way, which might provide a novel therapy for acute myeloid leukemia. (banglajol.info)
  • Duan P, Huang Y, Chen K, Cheng C, Wu Z, Wu Y. 15,16-dihydrotanshinone I inhibits EOMA cells proliferation by interfering in posttranscriptional processing of hypoxia-inducible factor 1. (banglajol.info)
  • The signal transducer and activator of transcription 5A (STAT5A) and STAT5B transcription factors have a conserved functional domain structure organized in N-terminal oligomerization, Coiled-coil, DNA-binding, Linker, SH2 and C-terminal transactivation domain. (nature.com)
  • Until now several members of the Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway have been implicated as being relevant for BAT physiology. (bvsalud.org)
  • Signal transduction and activator of transcription 5 (STAT5) is a member of the Jak/STAT signal transduction pathway and is activated by a variety of cytokines (IL22, IL6, IFN-α). (rndsystems.com)
  • A high-throughput assay for signal transducer and activator of transcription 5b based on fluorescence polarization. (mpg.de)
  • Studies have shown that all type I IFNs exclusively bind to and signal through ubiquitously expressed heterodimeric transmembrane (TM) receptors composed of two subunits-IFNAR1 and IFNAR2 [ 3 ], which are constitutively associated with tyrosine kinases TYK2 and JAK1/STAT2 (signal transducer and activator of transcription 2), respectively, under normal physiological conditions [ 4 , 5 ]. (scientificarchives.com)
  • 3 STAT5 regulated signaling controls important functions of innate and acquired immunity, hematopoiesis, and also growth and survival of many cell types in different organs responding to extracellular cytokines. (nature.com)
  • In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. (thermofisher.com)
  • Although the expression of MHC class I and II molecules can be upregulated by MSC exposure to inflammatory cytokines interferon-gamma (IFN- γ ) and tumor necrosis factor-alpha (TNF- α ), they are still unable to induce an immunological response [ 18 ]. (hindawi.com)
  • IL-5, IL-3, and GM-CSF are hematopoietic cytokines that are key mediators of the allergic inflammatory response. (tamu.edu)
  • O'Shea, John J. 1998-04-01 00:00:00 ▪ Abstract Cytokines and interferons are molecules that play central roles in the regulation of a wide array of cellular functions in the lympho-hematopoietic system. (sagepub.com)
  • Furthermore, senescent cells, with the secretory features known as the senescence-associated secretory phenotype (SASP), could produce proinflammatory cytokines, such as tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), and monocyte chemoattractant protein1 (MCP-1), to greatly affect the neighboring cells [ 17 , 18 ]. (hindawi.com)
  • STAT5 is activated by FLT3-ITD, which is a constitutively active TK driving the pathogenesis of acute myeloid leukemia (AML). (bvsalud.org)
  • While the inflammatory transcription factor nuclear factor of activated T-cells 2 ( NFAT2 , NFATC1 ) is overexpressed in AML, it is unknown whether it plays a role in FLT3 ITD -induced HSC transformation. (biomedcentral.com)
  • We generated a triple transgenic mouse model, in which tamoxifen-inducible Cre-recombinase targets expression of a constitutively nuclear transcription factor NFATC1 to FLT3 ITD positive HSC. (biomedcentral.com)
  • Interleukin 3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells. (wikipedia.org)
  • Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways. (ca.gov)
  • Dlx1&2 and Mash1 transcription factors control striatal patterning and differentiation through parallel and overlapping pathways. (ca.gov)
  • Runt-related transcription factors (RUNXs), RUNX1-3, are the master regulators of development and differentiation and are all important to the development of immune cells. (bjbms.org)
  • IL-7 is necessary to specify CD8 lineage differentiation during CD4/CD8 cell fate choice in the thymus by inducing expression of the transcription factor Runx3. (biolegend.com)
  • Signal transducers and activators of transcription as targets for small organic molecules. (mpg.de)
  • It can stimulate transcription factor c‑myc (activation of gene expression) and Ras pathway (suppression of apoptosis). (wikipedia.org)
  • Post-translational modifications might contribute to enhanced STAT5 activation in the context of transformation, but the strength and duration of pYSTAT5 are incompletely understood. (nature.com)
  • 7 The JAKs also trigger the activation and tyrosine phosphorylation of STAT5, causing parallel dimerization, nuclear translocation and tetramerization of STAT5. (nature.com)
  • AC-4-130 directly binds to STAT5 and disrupts STAT5 activation, dimerization, nuclear translocation, and STAT5-dependent gene transcription. (bvsalud.org)
  • Accordingly, differential activation of the downstream signaling by four mutants was observed and constitutively active STAT5 or AKT instead of STAT3 partially compensated MPL515/625/630 function. (biomedcentral.com)
  • Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2. (jak-stat.at)
  • Activation of STAT5 alpha in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. (thermofisher.com)
  • Formation of the cytokine receptor / JAK signaling complex and activation of JAK kinases leads to the phosphorylation of receptor chains, which creates docking sites for STAT ( S ignal T ransducers and A ctivators of T ranscription) transcription factors. (openrheumatologyjournal.com)
  • Upon cytokine activation receptor chain- bound STATs are then phosphorylated on the tyrosine residues, which results in dimerisation of STAT proteins that translocate to the nucleus and activate gene transcription. (openrheumatologyjournal.com)
  • They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
  • Lastly, IL-21 also promotes activation of the STAT3 promoter and other transcriptional factors. (intechopen.com)
  • Activation of FLT3, STAT5, and Mcl-1 expression was analyzed by western blotting. (banglajol.info)
  • JAK2 dependent phosphorylation and activation of the transcription factor STAT5 is a prominent outcome of TPOR activation, and it is the signaling pathway exploited by the reporter cells included in this assay. (indigobiosciences.com)
  • IL-3/Receptor complex induces JAK2/STAT5 cell signalization pathway. (wikipedia.org)
  • We hypothesize that IL-3 activates a JAK2/Raf-1 signaling pathway that is required for DUB-1 induction and is independent of STAT5. (ox.ac.uk)
  • CBL exon 8/9 mutants activate the FLT3 pathway and cluster in core binding factor/11q deletion acute myeloid leukemia/myelodysplastic syndrome subtypes. (jax.org)
  • FLT3 ligand-dependent hyperproliferation of CBL mutant cells could be abrogated by treatment with the FLT3 PTK inhibitor PKC412 (midostaurin).CBL exon8/9 mutants occur in genetically defined AML/MDS subtypes and transform hematopoietic cells by constitutively activating the FLT3 pathway. (jax.org)
  • The Type I IFN-induced PI3K pathway is involved in the production of antiviral effectors and in the regulation of the transcription and translation of ISGs [ 19 ]. (scientificarchives.com)
  • Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. (biomedcentral.com)
  • Type I IFN- activated STAT1 can also form a homodimer known as IFNγ-Activated Factor (GAF), which migrates into the nucleus, and binds to IFNγ-Activated Sequences (GAS), to induce proinflammatory genes [ 10 , 11 ]. (scientificarchives.com)
  • This STAT5-CrkL complex translocates into the nucleus, binds to GAS elements, and induces growthinhibitory genes [ 17 , 18 ]. (scientificarchives.com)
  • Activated STAT5 binds to its consensus GREs to initiate the formation of a complete transduction complex that drives expression of the Luc reporter gene. (indigobiosciences.com)
  • Erythropoietin (EPO), Granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-6. (wikipedia.org)
  • The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. (biomedcentral.com)
  • IL-7 induces anti-apoptotic factors Bcl2 and Bcl-xL and inhibiting pro-apoptotic factors such as Bad and Bax. (biolegend.com)
  • We found that O-GlcNAcylation and tyrosine phosphorylation act together to trigger pYSTAT5 levels and oncogenic transcription in neoplastic cells. (nature.com)
  • The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. (nature.com)
  • Our data show that O-GlcNAcylation of STAT5 is an important process that contributes to oncogenic transcription through enhanced STAT5 tyrosine phosphorylation and oligomerization driving myeloid transformation. (nature.com)
  • The oncogenic potential of identified mutants was evaluated in hematopoietic cells.We identified 3 of 279 AML/MDS patients expressing CBL exon 8/9 deletion mutants. (jax.org)
  • Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia. (childrensmercy.org)
  • The activated JAK proteins in turn phosphorylate specific residues on the IL-7R creating docking sites for signaling molecules such as STAT5 and to a lesser extent STAT1 and STAT3. (biolegend.com)
  • Type I IFN activated STAT1 and STAT2 also form other heterodimers, including STAT1-STAT3, STAT1-STAT4, STAT1-STAT5, and STAT2-STAT3 in specific cell types such as endothelial cells or cells of lymphoid origin [ 3 , 12 - 14 ]. (scientificarchives.com)
  • Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. (ca.gov)
  • Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. (ca.gov)
  • Thrombopoietin (TPO), the physiological activator of TPOR, is a glycoprotein that regulates thrombopoiesis, the process of platelet production, as well as hematopoietic stem cell maintenance. (indigobiosciences.com)
  • Hematopoietic colony-stimulating factor priming does not influence survival in acute myeloid leukemia: a meta-analysis of randomized trials. (childrensmercy.org)
  • High expression of myocyte enhancer factor 2C (MEF2C) is associated with adverse-risk features and poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group. (childrensmercy.org)
  • In the early 1960s Ginsberg and Sachs discovered that IL-3 is a potent mast cell growth factor produced from activated T cells. (wikipedia.org)
  • The cytokine was originally discovered via the observation that it induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3 (IL-3). (wikipedia.org)
  • Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. (nature.com)
  • O-GlcNAcylation of STAT5 could be required for nutrient sensing and metabolism of cancer cells. (nature.com)
  • 18 Both enzymes, OGT and OGA as well as multiple O-GlcNAcylated proteins are enriched at sites of active transcription in human cells. (nature.com)
  • Since STAT5 is a critical mediator of diverse malignant properties of AML cells, direct targeting of STAT5 is of significant clinical value. (bvsalud.org)
  • The mouse counterpart of STAT5 alpha is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this protein in cells. (thermofisher.com)
  • One such TF is the nuclear factor of activated T-cells ( NFAT ). (biomedcentral.com)
  • Therefore, damaging the MECs layer resulted in the release of various factors (such as SDF1/CXCL12, CXCL14, MMP, and tenascin) [ 11 , 12 ] with a potential to modify the tumour microenvironment and facilitate the paracrine communication between the tumour epithelial cells and the enclosed stroma enhancing the tumour aggressiveness [ 11 , 13 ]. (biomedcentral.com)
  • Mouse IL-7 was initially described as a pre B-cell grow factor expressed in bone marrow stromal cells. (biolegend.com)
  • In adult mice, IL-7/IL-7R signaling up regulates expression of early B cell factor (EBF), and EBF in turn regulates expression of B cell-specific genes required for the transition from lymphoid progenitor to pro-B cells. (biolegend.com)
  • Another negative regulator of hematopoietic cell development and function is SHP-1 (SRC homology 2 (SH2)-containing tyrosine phosphatase 1), that is mainly expressed in hematopoietic and lymphoid cells [ 8 ]. (biomedcentral.com)
  • Debierre-Grockiego F. Anti-apoptotic role of STAT5 in haematopoietic cells and in the pathogenesis of malignancies. (banglajol.info)
  • These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. (explorationpub.com)
  • Mock' reporter cells, which contain the STAT5-Luc reporter gene, but lack expression of TPOR, were similarly treated with TPO. (indigobiosciences.com)
  • Specifically, INDIGO's Reporter Cells contain the luciferase reporter gene functionally linked to an engineered minimal promoter sequence with upstream tandem STAT5 genetic response element (GRE) sequences. (indigobiosciences.com)
  • O-GlcNAcylation regulates the transcriptional activity of p53, c-Myc, FoxO1 and CREB, as well as components of the basal transcription machinery, for example, the C-terminal domain of RNA polymerase II. (nature.com)
  • 15 The dynamic addition and removal of O-GlcNAc has been described for multiple cytoplasmic and nuclear proteins and it affects the function of various signaling molecules and transcription factors. (nature.com)
  • The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. (cancerindex.org)
  • In astrocytes the OGD enhanced the nuclear translocation of hypoxia-inducible factor 1 (HIF-1), the major transcription factor regulating EPO expression. (jneurosci.org)
  • IL-3 shares the β subunit with IL-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF). (wikipedia.org)
  • Over the last decade it has become clear that EPO acts as growth and survival factors for multiple tissues expressing the EPO receptor [ 1 ]. (biomedcentral.com)
  • A dominant-negative form of STAT5 (truncated at amino acid 650) inhibited the induction of GAS-luc but not DUB-1-luc. (ox.ac.uk)
  • The amino acid sequences of STAT5 alpha and STAT5 beta show 96% sequence similarity, and both proteins are co expressed in most tissues in virgin and lactating mice. (thermofisher.com)
  • STAT5 has two isoforms (A and B) that share 93% amino acid identity and bind the DNA consensus site TTCN3GAA. (rndsystems.com)
  • MECs were found to express numerous proteinase inhibitors, anti-angiogenic factors, and tumour suppressors proteins. (biomedcentral.com)
  • Discovery of chromone-based inhibitors of the transcription factor STAT5. (mpg.de)
  • The transcription factor STAT5 is an essential downstream mediator of many tyrosine kinases (TKs), particularly in hematopoietic cancers. (bvsalud.org)
  • Both are linked to transformation due to deregulated kinase/phosphatase signaling or STAT5 gain-of-function (GOF) mutations. (nature.com)
  • Using primary hippocampal neurons from Stat5a/b knock-out mice we have recently shown that the presence of functional Stat5 is required for the trophic but not for the protective effect of EPO against glutamate-induced toxicity [ 9 ]. (biomedcentral.com)
  • No aberrations were found in normal hematopoietic tissues. (jax.org)
  • The binding of a growth factor brings the multiple monomeric receptor chains into close proximity resulting into the trans-phosphorylation of their cytoplamic domains, which consequently activates downstream signaling cascades. (openrheumatologyjournal.com)
  • 2010 ). The majority of SCN patients with leukemic progression show the appearance of hematopoietic clones with somatic mutations in CSF3R , resulting in a truncated form of CSF3R with defective internalization and aberrant signaling properties ( Touw, 2015 ). (molcells.org)
  • While some signals are mitogenic and proosteogenic, others function to inhibit osteogenesis and increase bone resorption, and it appears that a well-controlled, delicate balance of inflammatory factors is necessary for proper fracture repair [ 3 - 6 ]. (hindawi.com)
  • This β subunit sharing explains the biological functional similarities of different hematopoietic growth factors. (wikipedia.org)
  • Here, we describe the development and preclinical evaluation of a novel, potent STAT5 SH2 domain inhibitor, AC-4-130, which can efficiently block pathological levels of STAT5 activity in AML. (bvsalud.org)
  • Increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic markers including uncoupling protein 1 (UCP1), while decreased stimulated lipolysis was linked to decreased protein kinase A (PKA) activity. (bvsalud.org)
  • We have recently identified a hematopoietic cell-specific immediate-early gene, DUB-1, that encodes a growth-regulatory deubiquitinating enzyme. (ox.ac.uk)
  • Western blot analysis of STAT5 alpha was performed by loading 20 µg of NIH/3T3 (lane1), A431 (lane2), K562 (lane3) and Ramos (lane4) cell lysate using Novex® NuPAGE® 4-12 % Bis-Tris gel (Product # NP0321BOX), XCell SureLock™ Electrophoresis System (Product # EI0002), Novex® Sharp Pre-Stained Protein Standard (LC5800), and iBlot® Dry Blotting System (IB21001). (thermofisher.com)
  • In hematopoietic cell lines 60% of the internalized EPO is re-secreted [ 29 ]. (biomedcentral.com)
  • Activated STAT1 and STAT2 monomers dimerize and interact with IRF9 (IFN-regulatory factor 9) in the cytoplasm, which is known as the ISGF3 (IFN-stimulated gene (ISG) factor 3) complex [ 1 , 7 ]. (scientificarchives.com)
  • Cellular aging or cellular senescence is the critical factor for the process of aging. (hindawi.com)
  • Additional post-translational modifications, such as ubiquitination, sumoylation, acetylation and glycosylation have been detected in STAT5. (nature.com)
  • RESULTS: We found that STAT5 is necessary for acute cold-induced temperature maintenance and the induction of lipid mobilization in BAT following ß3-adrenergic stimulation. (bvsalud.org)
  • As part of civil aviation safety research into aeromedical factors impacting flight safety, we have undertaken a time course study on the effects of acute ethanol exposure to the legal intoxication level of blood alcohol concentration (BAC), 0.08 g/dL (0.08% wt/vol), on human gene expression in non-chronic users. (biomedcentral.com)
  • Previous reports indicate that the mechanisms of DN involve a multifactorial interaction of metabolic and hemodynamic factors such as high blood glucose, advanced glycation end-products (AGEs), and the renin-angiotensin system (RAS). (hindawi.com)
  • STAT5 alpha is critically involved in a variety of physiological functions, including reproduction, lactation, immune function and somatic growth. (thermofisher.com)
  • It also opens a new way of thinking for biomedical scientists, whether RNA modification will be another important factor to regulate the biological development of neoplastic diseases. (biomedcentral.com)