• Phosphorylation on tyrosine 705 by JAK1 and JAK2 is essential for STAT3 dimer formation, nuclear translocation, and DNA binding activity. (thermofisher.com)
  • Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. (neobiotechnologies.com)
  • Upon leptin stimulation the phosphorylation of STAT3 is one of the key events in JAK2-STAT3 pathway, followed by the dimerization and nuclear translocation of this molecule. (biomedcentral.com)
  • This review comprehends literatures on leptin and leptin resistance and especially discusses what STAT3 phosphorylation would contribute to central leptin resistance. (biomedcentral.com)
  • Intersecting analysis, molecular docking, and pathway validation analysis showed that risperidone influences the adipocytokine signaling pathway by targeting MAPK14 (mitogen-activated protein kinase 14), MAPK8 (mitogen-activated protein kinase 8), and RXRA (retinoic acid receptor RXR-alpha), thereby inhibiting long-chain fatty acid β-oxidation by decreasing STAT3 (signal transducer and activator of transcription 3) expression and phosphorylation. (frontiersin.org)
  • Risperidone inhibits leptin-mediated phosphorylation of STAT3-Y705, leading to weight gain ( 26 ). (frontiersin.org)
  • In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. (vinomis.com)
  • Canonically, the binding of ligands to their cognate receptors leads to the recruitment and phosphorylation of tyrosine kinases, which in turn recruit and phosphorylate STAT3 at Tyr705 (4). (abwizbio.com)
  • Upon phosphorylation, STAT3 proteins dimerize and translocate to the nucleus where they bind to promoter elements of target genes and modulate their transcription (4). (abwizbio.com)
  • In addition ot Tyr705 phosphorylation, Ser727 is required for maximal activation although Tyr705 phopsohrylation plays a key activating role (7,8). (abwizbio.com)
  • Ser727 phosphorylation can also stimulate mitochondrial STAT3, where it may trigger oxidative phosphorylation (9), confer stress protection by reducing reactive oxygen species (ROS) accumulation and apoptosis (10,11) and support Ras-induced malignant transformation (12). (abwizbio.com)
  • Mechanistically, knockdown resulted in decreased activation from the JAK2/STAT3 pathway, inhibition of STAT3 phosphorylation and decreased transcription of STAT3 focus on genes [85]. (morainetownshipdems.org)
  • We found that cutaneous T-cell lymphoma cells display activation of the interleukin-2 receptor/cytokine common chain-associated Jak/STAT signal transduction pathway that is transient in the early stage of the lymphoma and constitutive in the late stage of the disease progression. (upenn.edu)
  • Leptin-activated leptin receptor (LepRb) signals in hypothalamus via several pathways, in which JAK2-STAT3 pathway, the most extensively investigated one, is considered to mediate the major action of leptin in energy regulation. (biomedcentral.com)
  • We also discovered that hsa_circ_0017728 might serve as a ceRNA to sponge miR-149 and indirectly regulated the IL-6/STAT3 signaling pathway in GC cell proliferation and apoptosis. (archivesofmedicalscience.com)
  • They also block STAT activation and target multiple components of the Jak/STAT pathway for Ubiquitin-mediated proteasomal degradation. (creativebiomart.net)
  • Fig.1 JAK-STAT pathway activation and its negative regulators. (creativebiomart.net)
  • Increased expression of miR-223 promotes abnormal activation of the Akt/mTOR pathway in several diseases, including pancreatic cancer and colorectal cancer [ 24 ]. (biomedcentral.com)
  • Six weeks post vaccination, PBMCs isolated from three individuals with the most extreme responses in each HR and LR groups and 3 unvaccinated controls, were either stimulated with phytohaemagglutinin, challenged with the vaccine or mock treated for 24 h, prior conducting transcriptional studies, gene ontology and pathway analyses. (biomedcentral.com)
  • Since the discovery of the JAK-STAT pathway over two decades ago, research investigations have clearly demonstrated that the JAK-STAT pathway plays a major role in many biological processes including proliferation, immunity, cellular activation, and differentiation to name just a few. (innspub.net)
  • While the JAK-STAT pathway is indispensable for normal cellular functions, it was also discovered that abnormal activation of the JAK-STAT signaling pathway significantly contributes to the formation and progression of many human carcinomas. (innspub.net)
  • However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. (arigobio.com)
  • They indicate that pathways involving STAT3, PI3K/AKT and, apparently, STAT5 are constitutively activated by this kinase. (upenn.edu)
  • Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. (innspub.net)
  • An increasing body of literature indicates that the activation of signal transducer and activator of transcription (STAT) family of nuclear transcriptional factors such as STAT3 may be deeply involved in the development of a number of tumours due to the deregulation of their intracellular pathways and successive acquirement of incapacity of cells to enter in apoptosis. (univr.it)
  • SPR (Surface Plasmon Resonance) analysis to study the direct interaction between these compounds and proteins deeply involved in STAT3/5 pathways such as cytokine-receptors, JAKs/Tyk or STAT3 proteins. (univr.it)
  • The small GTPase Rac1 has been shown to bind and regulate the activity of STAT3 while the PIAS3 protein is a specific inhibitor of STAT3. (thermofisher.com)
  • Conversely, the STAT3-shRNA attenuated the increased tumor angiogenesis caused by the miR-874-inhibitor. (oncotarget.com)
  • Regulation and function of STAT3 in the ALK+ T-cells and testing an ALK-inhibitor small molecule candidate are the main focus of the ongoing investigation. (upenn.edu)
  • Effect of the STAT3 inhibitor STX-0119 on the proliferation of cancer stem-like cells derived from recurrent glioblastoma. (innspub.net)
  • the first vector was either the IKK-3 Inhibitor or mutants augmented STAT5 transcriptional activity and neither nor inspired STAT5 activation in cooperation using the mutants. (mergullo.net)
  • These elements are frequently found near gene enhancers and interact with nuclear matrix proteins to provide a unique nuclear microenvironment for transcriptional regulation. (wikipedia.org)
  • STAT3 belongs to the family of STAT (signal transducers and activators of transcription) proteins which are phosphorylated by receptor associated kinases, translocate to the nucleus, and act as transcription factors in response to cytokines and growth factors. (thermofisher.com)
  • 8, 9] STAT3 is one of 7 human STAT (signal transducer and activator of transcription) proteins, which are critical second messengers for many cytokine, hormone, and growth factor receptors. (medscape.com)
  • As proteins that interact with STAT3 may be key in addressing how STAT3 contributes to cancer pathogenesis, we took a proteomics approach to identify novel STAT3-interacting proteins. (unh.edu)
  • miRNAs are small, non-coding and single-stranded RNAs (approximately 22 nucleotides) and function as post-transcriptional regulators to modulate gene expression by sequence-specific interaction with their 3′-untranslated regions (3′-UTRs) [ 14 ]. (archivesofmedicalscience.com)
  • They are important post-transcriptional regulators of gene expression in plants, metazoans, and mammals, and are predicted to control the activity of 30% of all protein-coding genes [ 2 ]. (biomedcentral.com)
  • Coactivators such as CREB-binding protein are required for the transcriptional activation by STAT3. (thermofisher.com)
  • The transcription factors associated with STAT3 are c-Jun and cyclic AMP-responsive enhancer binding protein (CREB). (thermofisher.com)
  • Furthermore, the levels of miR-874 were inversely correlated with those of STAT3 protein in GC tissues. (oncotarget.com)
  • At 6 h after MCAO, IL-6RA administration had resulted in a significant reduction in the amount of phosphorylated signal transducer and activator of transcription-3 (Stat3) protein in the peri-infarct area of the cortex. (elsevierpure.com)
  • Granulin, a novel STAT3-interacting protein, enhances STAT3 transcriptional function and correlates with poorer prognosis in breast cancer. (unh.edu)
  • We identified granulin (GRN) as a novel STAT3-interacting protein that was necessary for both constitutive and maximal leukemia inhibitory factor (LIF)induced STAT3 transcriptional activity. (unh.edu)
  • These studies identify GRN as a functionally important STAT3-interacting protein that may serve as an important prognostic biomarker and potential therapeutic target in breast cancer. (unh.edu)
  • Additionally, STATT can recruit protein phosphatases to dephosphorylate and inactivate STAT3, further attenuating its activity. (creativebiomart.net)
  • We recognize Fam3a, a cytokine-like protein, as a significant Stat3 downstream effector in muscle tissue stem cells. (mdm-inhibitors.com)
  • Since STAT3 are nuclear factors regulating the expression of genes intricately involved in neoplasia, analysis of gene/protein profiles before and after treatment with anti-STAT3 pro-apoptotic phytocompounds will also be performed either by qRT-PCR methods or proteomics, this latter in a strict collaboration with Roman group. (univr.it)
  • Chromatin immunoprecipitation (ChIP) assay in C2C12 myoblasts demonstrated that Stat3 is certainly recruited to the site upon IL-6 excitement, which promotes Stat3 activation and translocation in to the nucleus (Fig.?2e). (mdm-inhibitors.com)
  • Its roles include regulation of proliferation, promotion of immune system and activation of apoptosis in B cells. (intechopen.com)
  • Taken together, these findings indicate that down-regulation of miR-874 contributes to tumor angiogenesis through STAT3 in GC, highlighting the potential of miR-874 as a target for human GC therapy. (oncotarget.com)
  • In the nucleus is involved in transcriptional regulation. (neobiotechnologies.com)
  • The major events in the regulation of the host response on a transcriptional level occur within the first 3 days after infection. (biomedcentral.com)
  • The LXXLL motif represents the minimal requirement for the interaction with the NFκB p65 subunit and for the inhibition of NFκB transcriptional activity. (wikipedia.org)
  • STAT3 inhibition suppressed the differentiation of osteopontin-producing MerTK + galectin-3 hi macrophages, however, STAT3 activation was insufficient at inducing Spp1 transcriptional activity. (elsevierpure.com)
  • ERK inhibition suppressed Spp1 transcriptional activation without affecting MerTK or galectin-3 expression. (elsevierpure.com)
  • The inhibition of Pin1 expression or its activity selectively reduced the transcriptional activities of full-length AR and AR-V7. (bcgsc.ca)
  • From many different viruses it really is renowned that they employ various apoptotic signaling elements inside the host cell for inhibition or activation of your endogenous suicide program. (pkainhibitors.com)
  • Whereas in the acute phase of the disease immunoregulatory processes prevail in the hippocampus and the cortex, we observed a strong activation of neurogenic processes in the hippocampal dentate gyrus, both by gene expression and immunohistology starting as early as 3 days after infection. (biomedcentral.com)
  • His research aimed to look at gene expression and gene reprogramming of transcriptional events using RNA sequencing to examine the changes found from deletion and activation for AML cells. (targetedonc.com)
  • We decided to dig deeper into a gene expression and gene reprogramming of transcriptional events in those myeloid cells using RNA sequencing analysis and looking at changes that are caused by a start with deletion, as well as by triggering activation of this receptor TLR9 that we use as a gateway into those cells, and by a combination of those 2 effects. (targetedonc.com)
  • Since the neoplastic phenotype of a cell is largely driven by aberrant gene expression patterns, increasing attention has been focused on transcription factors that regulate critical mediators of tumorigenesis such as signal transducer and activator of transcription 3 (STAT3). (unh.edu)
  • In primary breast cancer samples, GRN mRNA levels were positively correlated with STAT3 gene expression signatures and with reduced patient survival. (unh.edu)
  • Hence, STAT3 transcriptional activity is inhibited by the physical prevention of its binding to target genes. (wikipedia.org)
  • STAT3 mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. (thermofisher.com)
  • Abnormal STAT3-mediated signal transduction has been observed in a large number of neoplasms, in which it induces anti-apoptotic and cell cycle progression mediating genes transcription. (pbkom.eu)
  • Signal transducer and activator of transcription 3 (STAT3) was initially showed to control acute-phase genes in response to interleukin-6 (IL-6) and epidermal growth factor (EGF) during inflammatory processes (1). (abwizbio.com)
  • More recently we determined that the constitutive Jak/STAT activation is due, at least in part, to the lack of expression of SHP-1 phosphatase, which normally down-regulates IL-2R/ c-mediated cell activating signals. (upenn.edu)
  • They are induced by STAT activation and act as a negative feedback loop to inhibit further signaling. (creativebiomart.net)
  • By attenuating the Jak/STAT signaling, they prevent excessive inflammation and immune cell activation. (creativebiomart.net)
  • STAT3 belongs to the STAT family of cytoplasmic transcription factors that induces cell membrane-mediated nuclear signal transduction in various cellular activities (2). (abwizbio.com)
  • Lastly, IL-21 also promotes activation of the STAT3 promoter and other transcriptional factors. (intechopen.com)
  • Non-canonically, STAT3 may function independent of Tyr705 and nuclear localization. (abwizbio.com)
  • By examining dysfunctional intracellular activation events researchers may identify specific molecular regulators of disease and develop interventions to prevent and treat particular diseases. (innspub.net)
  • MerTK + galectin-3 hi macrophages showed a strong activation of both STAT3 and ERK (extracellular signal-regulated kinase). (elsevierpure.com)
  • 2005. A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells. (innspub.net)
  • It competes with STAT3 for binding to cytokine receptors, preventing the activation of STAT3 signaling. (creativebiomart.net)
  • Upon cytokine and growth factor stimulation STAT3, a transcription factor, is activated. (abwizbio.com)
  • Originally, PIAS3 was found to interact specifically with phosphorylated STAT3 in Interleukin -6 (IL-6) activated murine myeloblast M1 cells. (wikipedia.org)
  • This interaction is mediated via PIAS3 binding to the STAT3 DNA binding domain. (wikipedia.org)
  • Within the PINIT domain, the PIAS382-132 region was isolated and characterized as an inhibitory domain that binds and inhibits both the MITF and STAT3 transcription factors. (wikipedia.org)
  • Interleukin-10 and macrophage colony-stimulating factor synergistically activated STAT3 and ERK and promoted the differentiation of osteopontin-producing MerTK + galectin-3 hi macrophages in bone marrow-derived macrophages. (elsevierpure.com)
  • The human proto-oncogene STAT3 encodes transcriptional factor that is essential for embryo- genesis, proliferation and differentiation of many cell types, in addition to organ regeneration and involu- tion. (pbkom.eu)
  • STAT3 plays role in early embryonic development, growth and differentiation of various adult tissues (4). (abwizbio.com)
  • Together, these results indicate that Fam3a is certainly a Stat3-governed secreted aspect that promotes muscle tissue stem cell oxidative fat burning capacity and differentiation, and shows that Fam3a is certainly a potential device to modulate cell fate options. (mdm-inhibitors.com)
  • We further noticed upregulation of on the mRNA level in MuSCs during myogenic differentiation in vitro, mirroring the appearance design of Stat3 (Fig.?2d). (mdm-inhibitors.com)
  • The induction of MerTK on galectin-3 hi macrophages is essential for their functional maturation including efferocytosis and Spp1 transcriptional activity. (elsevierpure.com)
  • CONCLUSIONS: Interleukin-10 and macrophage colony-stimulating factor act synergistically to activate STAT3 and ERK in cardiac macrophages, which in turn upregulate the expression of galectin-3 and MerTK, leading to the functional maturation of osteopontin-producing macrophages. (elsevierpure.com)
  • Brevilin A, a novel natural product, inhibits janus kinase activity and blocks STAT3 signaling in cancer cells. (innspub.net)
  • 2002. Stat3 activation in prostatic carcinomas. (innspub.net)
  • The following product was used in this experiment: STAT3 Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-86074, RRID AB_2802874. (thermofisher.com)
  • Flow cytometric analysis of Jurkat cells secondary antibody only negative control (blue) untreated (red) treated with IFNα IL-4 and pervanadate (green) treated + blocked with phospho-peptide (brown) using Phospho-Stat3 (Tyr705) antibody Stat3Y705-B12 (5 ng/mL) Cat. (abwizbio.com)
  • Deletion of the STAT3 gene in knock-out mice was lethal at the early embryonic stage. (thermofisher.com)
  • What was really interesting was that RNA sequencing data has basically shown us that neither of these effects alone, so TLR9 activation nor STAT3 deletion alone, had the same effect as a combination of these 2 effects. (targetedonc.com)
  • Blocking androgen receptor (AR) transcriptional activity by androgen deprivation therapy (ADT) improves the response to radiotherapy for intermediate and high risk prostate cancer. (bcgsc.ca)
  • Recently, we have identified two terpenes isolated from laurel leaves, custunolide and dehydrocostus lactone, with a strong anti-STAT3 activity. (univr.it)
  • We also have identified certain plant extracts with anti-STAT3 activity and we are going to identify the responsible compounds. (univr.it)
  • This study is aimed to correlate pro-apoptotic activity of some phytocompounds to their anti-STAT3/5 activity. (univr.it)
  • Phosphorylated STAT3 (p-STAT3), as a transcription factor, binds to and regulates its target gene such as POMC gene, playing the physiological function of leptin. (biomedcentral.com)
  • We present that myogenic cells secrete Fam3a, and publicity of Stat3-ablated muscle tissue stem cells to recombinant Fam3a in IDO-IN-5 vitro and in vivo rescues their defects in mitochondrial respiration and myogenic dedication. (mdm-inhibitors.com)
  • We performed mass spectrometry-based profiling of STAT3-containing complexes from breast cancer cells that have constitutively active STAT3 and are dependent on STAT3 function for survival. (unh.edu)
  • Citation: Ding Z, Cao J, Shen Y, Zou Y, Yang X, Zhou W, Guo Q and Huang C (2018) Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury. (vinomis.com)
  • Right here we demonstrate that Stat3 promotes muscle tissue stem cell myogenic lineage development by stimulating mitochondrial respiration in mice. (mdm-inhibitors.com)
  • Regarding POMC gene in hypothalamus however little is known about the detail of its interaction with STAT3. (biomedcentral.com)
  • Synthetic peptide, corresponding to amino acids 680-720 of Human Stat3. (thermofisher.com)
  • Mutations in the STAT3 gene cause most cases of AD-HIES. (medscape.com)
  • In 2007, autosomal dominant mutations in signal transducer and activator of transcription-3 (STAT3) gene were identified as the molecular cause of this disease. (medscape.com)
  • STAT3 gene is diagrammed with depiction of hotspots (areas where higher numbers of patients were noted to have mutations). (medscape.com)
  • Mutations in the STAT3 gene have been identified in almost all cases of clinically verified autosomal dominant hyper-IgE syndrome (AD-HIES). (medscape.com)
  • STAT3 mutations have been found in persons of Asian, African, Caucasian, and Hispanic descent and correlate well with HIES disease. (medscape.com)
  • Due to AML always progressing and being very heterogeneous, a molecule targeting STAT3 in AML cells was developed. (targetedonc.com)
  • These results suggest that endogenous IL-6 plays a critical role in preventing damaged neurons from undergoing apoptosis in the acute phase of cerebral ischemia and that its role may be mediated by Stat3 activation. (elsevierpure.com)
  • Marcin Kortylewski, PhD, discusses some of the goals and findings of his research on blocking STAT3 in acute myeloid leukemia cells. (targetedonc.com)
  • Marcin Kortylewski, PhD, a professor in the Department of Immuno-Oncology at the City of Hope Comprehensive Cancer Center, discusses some of the goals and findings of his research on blocking STAT3 in acute myeloid leukemia (AML) cells. (targetedonc.com)
  • Overexpression of STAT3 rescued the loss of tumor angiogenesis caused by miR-874. (oncotarget.com)
  • What Kortylewski found was that a rapid regression in leukemia was linked to blocking STAT3 in these AML cells, caused by immune mediated circulating tumor DNA responses. (targetedonc.com)
  • Three alternatively spliced transcript variants encoding distinct isoforms of STAT3 have been described. (thermofisher.com)
  • miRNA-132 acts as an angiogenic switch by suppressing endothelial p120RasGAP expression, leading to Ras activation and the induction of neovascularization [ 9 ]. (oncotarget.com)
  • Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting? (mdpi.com)
  • GRN enhanced STAT3 DNA binding and also increased the time-integrated amount of LIF-induced STAT3 activation in breast cancer cells. (unh.edu)
  • Emerging evidence provided insight into the role of signal transducer and activator of transcription 3 (STAT3) in energy metabolism. (biomedcentral.com)
  • Interleukin-10- STAT3 (signal transducer and activator of transcription 3)- galectin-3 axis is essential for Spp1 (encoding osteopontin) transcriptional activation in cardiac macrophages after MI. (elsevierpure.com)
  • These changes seem to be a driver of immune activation that we see in this model. (targetedonc.com)
  • Augmented STAT3 activation has been found in both irreversibly committed B cell lineage precursors and plasmacy- tes. (pbkom.eu)
  • Moreover the status of p-STAT3 and its significance in hypothalamus of DIO mice needs to be well elucidated. (biomedcentral.com)
  • In addition, STAT3 is shown to promote pathogenic roles in cancer initiation, progression, metastasis, chemoresistance and immunoevasion (5). (abwizbio.com)
  • Through reporter gene and western blot assays, STAT3 was shown to be a direct target of miR-874. (oncotarget.com)
  • In parallel we will study the molecular mechanism of anti-STAT3 action of these compounds by identifying their direct target molecules. (univr.it)