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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Signal transduction in eukaryotic cells is a complex process mediated, normally, by the interaction of soluble extrinsic protein factors and their cognate receptors. One example of this phenomena is the inflammatory cytokine interleukin-6 and the IL-6 receptor. However, the IL-6 receptor, once its ligand is bound, associates with another membrane glycoprotein, gp130, to potentiate the cytokine response. To further understand the basis of this interaction, and its possible implications in cellular transforming events, the corresponding gene(s) must be studied. Here we find that the human gp130 gene product is homologous to two distinct chromosomal loci on chromosomes 5 and 17. Furthermore, the presence of two distinct gp130 gene sequences is restricted to primates and is not found in other vertebrates.
Somat Cell Mol Genet 1992 Sep
PMID:Chromosomal localization of the IL-6 receptor signal transducing subunit, gp130 (IL6ST). 147 13

Interleukin-6 (IL-6) relays an important signal to hepatocytes during the early stages of an acute inflammatory response, causing an alteration in the expression of several major defense proteins. Additional regulation of this signal could occur either by altering the number of IL-6 receptors (IL-6-R) or of the signal transducing protein, gp130. We employed ribonuclease protection assays to measure the expression of IL-6-R and gp130 mRNA in primary rat hepatocytes in response to IL-6, interleukin-1, dexamethasone, and combinations thereof. Dexamethasone increases receptor mRNA levels 2.7-fold above controls but has no detectable effect on that of gp130. Such treatment increased surface expression of IL-6-R from 600 receptors per cell to greater than 6000, without a change in Kd (2.5-4.6 x 10(-10) M). In contrast to the stimulatory effect of the steroid signal, the inflammatory cytokines, individually and together, down-modulated both the mRNA and the cell surface expression of IL-6-R. These findings demonstrate for the first time that a sensitive control system exists between inflammatory mediators and IL-6-R.
Mol Biol Cell 1992 Jan
PMID:Differential regulation of interleukin-6 receptor and gp130 gene expression in rat hepatocytes. 155 Sep 52

DNA sequences encoding a human melanoma membrane-bound sialoglycoprotein of 130,000 molecular weight (gp130) were introduced into a clonal derivative of mouse B-16 melanoma cells with the selectable neomycin resistance gene (aminoglycoside phosphotransferase). Mouse transfectants were identified by a rapid and precise screening method with mouse monoclonal antibodies and erythrocyte rosetting. The frequency of gp130 transfectants was approximately 1 in 2,000 to 5,000 colonies with neo+ cells. Analysis of secondary mouse transfectants has revealed that the transfected gp130 has a molecular weight, isoelectric point, intracellular processing, peptide map, and spatial orientation of surface-exposed epitopes indistinguishable from those seen with gp130 from human melanoma cells. In contrast to primary transfectants, secondary transfectants expressing gp130 lack demonstrable human repetitive sequences.
Mol Cell Biol 1985 Apr
PMID:DNA-mediated transfer of human melanoma cell surface glycoprotein gp130: identification of transfectants by erythrocyte rosetting. 399 Jun 90

Ciliary neurotrophic factor (CNTF) is a cytokine sharing structural and functional similarities with interleukin-6 (IL-6) and other helical cytokines that utilize the common signalling chain gp130. While IL-6 induces gp130 dimerization, CNTF, after the initial interaction with the specific, non-signalling receptor subunit, CNTFR, induces the formation of gp130/LIF-receptor heterodimers. Through immunoprecipitation experiments with tagged soluble receptor molecules, we recently demonstrated that IL-6 drives the formation of a hexameric receptor complex with a defined topology and composed of two IL-6, two IL-6R alpha and two gp130 molecules. Here, we apply the same strategy to study the assembly in vitro of the CNTF receptor complex. We present evidence that both the cytokine and the specific binding chain undergo dimerization in the presence of gp130. Furthermore, although gp130 and LIFR are able to bind independently to the CNTF/CNTFR sub-complex, they never form homodimers but only heterodimers. We propose that CNTF assembles a hexameric receptor complex composed of two CNTF, two CNTFR, one gp130 and one LIFR molecule, and present a model of the reciprocal interaction of these molecules based on similarities with the IL-6 hexameric complex.
J Mol Biol 1995 Dec 15
PMID:In vitro binding of ciliary neurotrophic factor to its receptors: evidence for the formation of an IL-6-type hexameric complex. 750 Mar 50

In addition to specific ligand binding elements, receptor assembly for interleukin(IL)-6, oncostatin-M, leukaemia inhibitory factor, ciliary neurotrophic factor and IL-11 includes an additional unit, gp130. This molecule is a transmembrane glycoprotein of 130 kDa. In this paper, reviewing molecular, biochemical and functional data on gp130, we describe the dissimilar action of IL-3 on the expression of the binding unit of the IL-6 receptor and that of gp130. According to FACS studies, resting basophils express only IL-6 receptors and no gp130 molecules on the plasma membranes. After incubation with IL-3, the surface appearance and de novo transcription of gp130 was shown by FACS and mRNA polymerase chain reaction analysis.
J Mol Recognit 1994 Dec
PMID:Separate regulation of a membrane protein, gp130, present in receptor complex specific for interleukin-6 and other functionally related cytokines. 773 54

Oncostatin M belongs to the subfamily of hematopoietin cytokines that binds a receptor complex containing gp130. To date, only the human form of oncostatin M has been identified, and its evolutionary conservation is unresolved. We have isolated a bovine gene whose open reading frame encodes a precursor protein that is 58% identical to human oncostatin M. A comparison of the bovine and human amino acid sequences predicts significant similarity, including the four-alpha-helical-bundle structure and the placement of disulfide bridges. As with the human protein, bovine oncostatin M binds specific receptors on human H2981 cells and inhibits the proliferation of human A375 tumor cells and mouse M1 leukemia cells. To identify activities regulated in vivo, we injected bovine oncostatin M fusion genes containing various tissue-specific promoters into mouse embryos. The frequencies of transgenic mice were reduced significantly, suggesting that overexpression of the bovine cytokine is detrimental to normal mouse development. In addition to deaths associated with expression in neurons and keratinized epithelia, bovine oncostatin M caused abnormalities in bone growth and spermatogenesis, stimulated fibrosis surrounding islets in the pancreas, and disrupted normal lymphoid tissue development. This work establishes the existence of a nonprimate oncostatin M gene and provides the first demonstration that this cytokine can function in a pleiotropic manner in vivo. Information regarding bovine oncostatin M may help characterize the structure and function of this cytokine in other vertebrate species.
Mol Cell Biol 1995 May
PMID:Developmental abnormalities in mice transgenic for bovine oncostatin M. 773 18

Recent evidence has shown that members of the Jak kinase family are activated after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6 cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in different cell types. Using monospecific antibodies to gp130, Jak2 kinase, and phosphotyrosine, we investigated the kinetics of IL-6 stimulation of members of this pathway in primary hepatocytes. Our findings show that Jak 2 is maximally activated within 2 min of exposure to IL-6, followed by gp130 phosphorylation that reaches its peak in another 2 min then declines to basal level by 60 min. In vitro phosphorylation experiments show that activated Jak 2 is able to phosphorylate both native gp130 and a fusion peptide containing its cytoplasmic domain, demonstrating gp130 is a direct substrate of Jak 2 kinase. Experiments designed to explore the cell surface expression of gp130 show that > or = 2 h are required to get a second round of phosphorylation after the addition of more cytokines. This finding suggests that activated gp130 is internalized from the cell surface after IL-6 stimulation. Additional experiments using protein synthesis inhibitors reveal that new protein synthesis is required to get a second cycle of gp130 phosphorylation indicating gp130 must be synthesized de novo and inserted into the membrane. These findings provide strong evidence that down regulation of the IL-6 signal in hepatocytes involves the internalization and cytosol degradation of gp130.
Mol Biol Cell 1994 Jul
PMID:Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes. 781 50

Gonadotropin regulation of granulosa cell (GC) differentiation can be modulated by non-steroidal factors, including cytokines. Interleukin-6 (IL-6), a broad spectrum cytokine, has been previously demonstrated to be produced by GCs and to directly influence follicle stimulating hormone (FSH) differentiated functions of ovarian GCs. In the present study, primary cultures of GCs were prepared from prepubertal sow ovaries. No significant amount of biological active IL-6 was detected in these cultures using the B9 cell growth bioassay. Although our findings suggest that GCs are not source of IL-6 in the porcine ovary, this cytokine may be released by leukocytes present in the ovary and modulate ovarian functions by acting on GCs. Here, adding recombinant human (rh)IL-6 to GC cultures inhibited differentiated functions induced by FSH such as aromatase activity, LH receptor (LHr) expression measured by specific 125I-hCG binding and progesterone (P) production. On the opposite, rhIL-6 did not modulate stimulatory human chorionic hormone (hCG) effects on P release by GCs and did not prevent hCG binding to LHr. These preliminary results clearly showed that IL-6 acted differently on FSH and hCG induced functions although these gonadotropins act primarily through the same transduction pathway involving generation of cyclic AMP. We suggest that IL-6 might act more likely by reducing FSH binding capacity than by modulating transduction pathways. Inhibitory IL-6 effects on FSH-induced functions were not neutralized by adding to culture media a monoclonal antibody against the human IL-6 signal transducer gp130, previously reported to inhibit IL-6 mediated effects in human cell lines.
Cell Mol Biol (Noisy-le-grand) 1994 May
PMID:Comparative IL-6 effects on FSH and hCG-induced functions in porcine granulosa cell cultures. 792 Jan 81

Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotropic factor are a family of cytokines and neuronal differentiation factors which bind to composite plasma membrane receptors sharing the signal transducing subunit gp130. We have shown recently that IL-6 and leukemia inhibitory factor rapidly activate a latent cytoplasmic transcription factor, acute-phase response factor (APRF), by tyrosine phosphorylation, which then binds to IL-6 response elements of various IL-6 target genes. Here we demonstrate that APRF is activated by all cytokines acting through gp130 and is detected in a wide variety of cell types, indicating a central role of this transcription factor in gp130-mediated signaling. APRF activation is also observed in vitro upon addition of IL-6 to cell homogenates. Protein tyrosine kinase inhibitors block both the tyrosine phosphorylation and DNA binding of APRF. The factor was purified to homogeneity from rat liver and shown to consist of a single 87-kDa polypeptide, while two forms (89 and 87 kDa) are isolated from human hepatoma cells. As reported earlier, the binding sequence specificity of APRF is shared by gamma interferon (IFN-gamma) activation factor, which is formed by the Stat91 protein. Partial amino acid sequence obtained from purified rat APRF demonstrated that it is likely to be related to Stat91. In fact, an antiserum raised against the amino-terminal portion of Stat91 cross-reacted with APRF, suggesting the relatedness of APRF and Stat91. Altogether, these data indicate that APRF belongs to a growing family of Stat-related proteins and that IFN-gamma and IL-6 use similar signaling pathways to activate IFN-gamma activation factor and APRF, respectively.
Mol Cell Biol 1994 May
PMID:The interleukin-6-activated acute-phase response factor is antigenically and functionally related to members of the signal transducer and activator of transcription (STAT) family. 816 74

The receptor for leukemia inhibitory factor (LIFR), in combination with the signal-transducing subunit for interleukin-6-type cytokine receptors, gp130, and LIF, activates transcription of acute-phase plasma protein genes in human and rat hepatoma cells and the vasoactive intestinal peptide gene in a human neuroblastoma cell line. To identify the regions within the cytoplasmic domain of LIFR that initiate signal transduction independently of gp130, we constructed a chimeric receptor by linking the extracellular domain of the granulocyte colony-stimulating factor receptor (G-CSFR) to the transmembrane and cytoplasmic domain of human LIFR. The function of the chimeric receptor protein in transcriptional activation was assessed by G-CSF-mediated stimulation of cotransfected cytokine-responsive reporter gene constructs in hepatoma and neuroblastoma cells. By using the full-length cytoplasmic domain and mutants with progressive carboxy-terminal deletions, internal deletions, or point mutations, we identified the first 150 amino acid residues of LIFR as the minimal region necessary for signaling. The signaling reaction appears to involve a cooperativity between the first 70-amino-acid region containing the two sequence motifs conserved among hematopoietin receptors (box 1 and box 2) and a critical sequence between residues 141 and 150 (box 3). Analogous analyses of the cytoplasmic domains of G-CSFR and gp130 indicated similar arrangements of functional domains in these receptor subunits and the requirement of a box 3-related motif for signaling.
Mol Cell Biol 1994 Jan
PMID:Multiple regions within the cytoplasmic domains of the leukemia inhibitory factor receptor and gp130 cooperate in signal transduction in hepatic and neuronal cells. 826 82


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