• STAT3
  • Large-scale screening of cancer cell lines with a JAK2 inhibitor that blocks STAT3 function revealed a more than 30-fold range in sensitivity in PDAC, and showed a close correlation of sensitivity with levels of tyrosine-phosphorylated STAT3 and of the gp130 receptor, an upstream signaling component. (aacrjournals.org)
  • Correspondingly, upregulation of the IL6/LIF-gp130 pathway accounted for the strong STAT3 activation in PDAC subsets. (aacrjournals.org)
  • Moreover, our work suggests that gp130 and phospho-STAT3 expression may be effective biomarkers for predicting response to JAK2 inhibitors. (aacrjournals.org)
  • 2018-04-13 00:00:00 Abstract Tumor necrosis factor receptor-associated factor 2 (TRAF2) and TRAF5 constitutively bind to glycoprotein 130 kDa (gp130) and inhibit IL-6-driven activation of signal transducer and activator of transcription 3 (STAT3) in CD4+ T cells, which limits the differentiation of pro-inflammatory IL-17-producing helper T cells that require IL-6-receptor (IL-6R) signals for their development. (deepdyve.com)
  • However, it is not known how the interaction between TRAF and gp130 negatively regulates STAT3 activity in the IL-6R complex. (deepdyve.com)
  • We hypothesized that TRAF proteins associated with gp130 might limit the activation of Janus kinase that is needed for the activation of STAT3. (deepdyve.com)
  • TRAF2 and TRAF5 constitutively bind to gp130 and inhibit IL-6-driven phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3). (deepdyve.com)
  • In naive CD4+ T cells, TRAF2 and TRAF5 work as negative regulators in the IL-6-receptor (IL-6R) signaling complex and limit the generation of pro-inflammatory IL-17-producing helper T cells (Th17 cells) that require activation of the IL-6-IL-6R-gp130-STAT3 signaling axis for their development (8, 9). (deepdyve.com)
  • The activated JAKs then phosphorylate the cytoplasmic tail of gp130 on specific tyrosine residues, generating binding sites for STAT transcription factors including STAT3. (deepdyve.com)
  • Recruitment of a STAT3 to the phosphorylated gp130 brings the STAT3 close to the activated JAK, which then phosphorylates a tyrosine residue of the STAT3 (10, 11). (deepdyve.com)
  • The signaling action of the OSM receptor has been defined by the suppression of proliferation through mediating G1 arrest in part by the induction of cyclin kinase inhibitors and to trigger induction as well as suppression of genes through transcription factors that include STAT3 and STAT5, AP-1/ATFs, C/EBP and CREB. (roswellpark.org)
  • 4 All IL-6 cytokines are potent activators of signal transducer and activator of transcription 3 (STAT3). (ahajournals.org)
  • Role of the gp130 receptor system and downstream mediator STAT3 in cardioprotection. (ahajournals.org)
  • Genes transcriptionally upregulated by STAT3 include SOCS proteins-1 and -3, which interact with the kinase domain of JAK proteins or cytoplasmic phosphotyrosine residue (phospho-Tyr759) of the receptor, resulting in inhibition of STAT protein phosphorylation and negative-feedback regulation of STAT activation. (ahajournals.org)
  • CT-1 (cardiotrophin 1) activates gp130 transducing components determine the interaction with members of the Jak / STAT pathway Janus kinase family, gp130 preferentially activated STAT1 and STAT3 , a consequence of imbalanced signals causes unexpected results . (wordpress.com)
  • IL-27 acts through a heterodimer receptor consisting of IL-27R α (WSX1) and gp130 chains, which mediate signaling predominantly through STAT1 and STAT3. (hindawi.com)
  • Stat3 is recruited to the activated LIF receptor and phosphorylated by Janus Kinase. (wikipedia.org)
  • proteins
  • The STAT proteins were originally identified as factors required for downstream signaling in response to interferon and other inflammatory cytokines ( 8 ). (aacrjournals.org)
  • CXCR1 and CXCR2 are proteins expressed on cells, including CSCs, which respond to the aforementioned cytokines in a deleterious manner. (blogspot.com)
  • Therefore, our results demonstrate that gp130-associated TRAF2 and TRAF5 inhibit the interaction between two JAK proteins in the IL-6R complex that is essential for initiating the JAK-STAT signaling pathway. (deepdyve.com)
  • The altered profile of cytokine responses in cancer cell types compared to the normal counterparts has allowed the identification of changes in the expression of signaling proteins (as in the case of myeloid leukemias) and cytokine receptors (as in the case of lung epithelial cells) as function of malignant transformation. (roswellpark.org)
  • Studies indicate that suppressors of cytokine signaling (SOCS) proteins CIS, SOCS1, and SOCS3 can be considered the third immunocheckpoint molecules since they regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells. (nih.gov)
  • The complex of these two proteins then associates with gp130. (wikipedia.org)
  • There are many other proteins which associate with gp130, such as cardiotrophin 1 (CT-1), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and IL-11. (wikipedia.org)
  • There are also several other proteins which have structural similarity to gp130 and contain the WSXWS motif and preserved cysteine residues. (wikipedia.org)
  • B, Tyrosine phosphorylation of JAKs and recruitment of STAT proteins to the gp130 receptor. (ahajournals.org)
  • Molecules currently under study include receptors of the immune system involved in autoimmune disorders (T cell receptors, co-receptors, MHC, cytokines), proteins involved in host-pathogen interactions and molecular mimicry (CMV and Toxoplasma surface antigens), proteins of nervous system (peptide hormone receptors, neural guidance proteins), and membrane proteins (chemokine receptors). (stanford.edu)
  • molecules
  • The cytokine-specific action determining the expression of intercellular adhesion molecules (ICAM), cytokines and chemokines in endothelial, stromal and epithelial cells as part of inflammation and fever response is identified in collaboration with members on the program for hyperthermia and photodynamic therapy. (roswellpark.org)
  • Title: Suppressors of cytokine signaling: Potential immune checkpoint molecules for cancer immunotherapy. (nih.gov)
  • chemokines
  • We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS. (paperity.org)
  • pathway
  • Cardiotrophin-1 and leukemia inhibitory factor act through the JAK/STAT pathway induced by gp130 to mediate cardiac hypertrophy and antiapoptosis. (ahajournals.org)
  • Many cytokines involved in RA, such as interleukin-18 (IL-18), IL-1, IL-6, and IL-17, exert their biologic effect through the JAK/STAT signaling pathway. (wiley.com)
  • soluble IL-6 recept
  • The ' extracellular region' comprises six units of a fibronectin type III module consists of three extracellular domains several immunoglobulin-like and the third membrane the proximal fibronectin-like domain in the presence of soluble IL-6 receptor ( sIL-6R - gp80 ). (wordpress.com)
  • membrane
  • These receptors are also known under the name hemopoietin receptors, and share a common amino acid motif (WSXWS) in the extracellular portion adjacent to the cell membrane. (wikipedia.org)
  • Once bound to IL-6, the resulting sIL-6R/IL-6 complex acts as an agonist that is capable of activating cells through membrane-bound gp130. (rupress.org)
  • regulators
  • Cytokines are major regulators of those evolutionarily conserved processes that determine, among others, the tissue response to injury, mediate inflammation, activate systemic acute phase reaction and fever, and direct the innate and adaptive immune responses. (roswellpark.org)
  • LIFR
  • citation needed] LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the inner cell mass. (wikipedia.org)
  • Cell Proliferation
  • The studies address two questions: (1) What are the mechanisms by which the heteromeric receptors for the interleukin 6 class cytokines - namely IL-6, IL-31, leukemia inhibitory factor (LIF) and oncostatin M (OSM) - control cell proliferation and the expression of differentiated genes? (roswellpark.org)
  • IL-27 was initially reported as an immune-enhancing cytokine that supports CD4 + T cell proliferation, T helper (Th)1 cell differentiation, and IFN- γ production, acting in concert with IL-12. (hindawi.com)
  • Structurally
  • Structurally, gp130 is composed of five fibronectin type-III domains and one immunoglobulin-like C2-type (immunoglobulin-like) domain in its extracellular portion. (wikipedia.org)
  • IL-27 is a pleiotropic two-chain cytokine, composed of EBI3 and IL-27p28 subunits, which is structurally related to both IL-12 and IL-6 cytokine families. (hindawi.com)
  • JAK1
  • In accordance with this, upon stimulation of endogenous gp130 with a complex of IL-6 and IL-6R, Traf5−/− CD4+ T cells displayed significantly higher amounts of phosphorylated JAK1 than did their wild-type counterparts. (deepdyve.com)
  • Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. (wikipedia.org)
  • Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. (wikipedia.org)
  • pleiotropic
  • These disappointing results may be due to several reasons, such as the multiplicity of cellular targets and the pleiotropic effects of these cytokines. (hindawi.com)
  • cardiotrophin
  • There is limited information available on biological effects of other IL-6-type cytokines, namely OSM, LIF, ciliary neurotrophic factor, neurotrophin-1, and cardiotrophin-1, in prostate cancer cells. (aacrjournals.org)
  • preferentially
  • Previous studies have shown that complexation of IL-2 with the JES6-1 Ab preferentially biases cytokine activity toward TReg cells through a unique mechanism whereby IL-2 is exchanged from the Ab to IL-2Ralpha. (stanford.edu)
  • inflammatory
  • IL-6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. (guidetopharmacology.org)
  • The information gain on inflammatory mediators and receptor functions in tissue culture model system are currently applied to the identification of regulatory processes in complex reconstituted systems using 3-dimensional cultures of primary cells isolated from the lung. (roswellpark.org)
  • Since the inflammatory potential of IL-6 is modulated through binding the sIL-6R, identifying physiological mediators of sIL-6R generation is of central importance to understanding the significance of this soluble receptor in disease. (rupress.org)
  • tumor
  • IL-8, another cytokine, is released after tumor cell death, subsequently stimulating CSCs to regrow the tumor and resist chemotherapy. (blogspot.com)
  • The first program has the overall goal of characterizing the cellular and molecular action of cytokines that mediated the local and systemic response to tissue damage and modulated tumor growth. (roswellpark.org)
  • The tumor-specific expression of cytokine receptor subunits is in part correlated with epigenetic alterations in DNA methylation and histone acetylation. (roswellpark.org)
  • Administration of anti-human IL11 receptor (R) α blocking antibody dramatically reduced HEC1A-derived tumor growth in both models and reduced peritoneal metastatic lesion spread in the orthotopic model, compared with IgG. (aacrjournals.org)
  • cellular
  • Curcumin has been found to not only block cytokine release, but their binding to these two cellular targets. (blogspot.com)
  • Splenic cellular responses were analyzed by measuring cytokine production, using Luminex multi-analyte technology. (wiley.com)
  • growth
  • Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bone metabolism, cachexia, neural development, embryogenesis and inflammation. (wikipedia.org)