Disease relevance of Il6st

• Similarly, CNTFR3alpha specifically antagonizes the induction of gp130 and LIFRbeta tyrosine phosphorylation observed in response to CNTF and wild type soluble CNTFRalpha in the HepG2 hepatoma cell line, as well as the subsequent events leading to haptoglobin synthesis [1].
• Exogenous LIF attenuates ischemic brain injury by activating cytokine signaling through LIFR/gp130 [2].
• Spatiotemporal distribution of gp130 cytokines and their receptors after status epilepticus: comparison with neuronal degeneration and microglial activation [3].
• At the early stages of regeneration (from 3 hr to Day 2 post contusion), significant signals for gp130 and LIFR mRNAs were detected in myonuclei and/or nuclei of muscle precursor cells (mpcs) and in mononuclear cells located in extracellular spaces between myofibers after muscle contusion, but IL-6R mRNA was expressed only in mononuclear cells [4].
• By quantitative real-time PCR, the mRNA expression of Rasa, Pi3kr1, Ccnh, and Il6st in carcinomas was, respectively, 22-, 20-, three- and threefold higher in carcinomas than in control mammary gland tissues (P<0.05, Student's t-test) [5].

High impact information on Il6st

• Primary osteoblasts constitutively expressed mRNAs for both IL-11 receptor (IL-11R alpha) and gp130 [6].
• These results suggest a central role of gp130-coupled cytokines, especially IL-11, in osteoclast development [6].
• We explored the signals required for neurite outgrowth of PC12 cells by using a series of mutants of a chimeric receptor consisting of the extracellular domain of the granulocyte-colony stimulating factor (G-CSF) receptor and the cytoplasmic domain of gp130, a signal-transducing subunit of the IL-6 receptor [7].
• POMC-specific gp130 knockout mice exhibit unaltered numbers of POMC cells and normal energy homeostasis under standard and high fat diet [8].
• Regulation of CCAAT/Enhancer binding protein, interleukin-6, interleukin-6 receptor, and gp130 expression during myocardial ischemia/reperfusion [9].

Biological context of Il6st

• These data indicate that ligands activating the gp130 pathway have the ability to profoundly alter neuronal cell shape and polarity by selectively causing the retraction of dendrites [10].
• When both forms of gp130 are deglycosylated the resulting core peptides migrate to identical positions in a denatured protein gel, indicating that the principal difference between the two forms resides in the extent of their glycosylation [11].
• The kinetics of gp130 maturation and surface expression were determined [11].
• Signals through gp130 upregulate Wnt5a and contribute to cell adhesion in cardiac myocytes [12].
• The nucleotide sequence of gp130 from a human B-cell line has been reported [13].

Anatomical context of Il6st

• We speculate that gp130 cytokines play a paracrine, neuromodulatory role in the hippocampus since both before and after seizure, principal cells appear to be the major cell type expressing the receptors for these cytokines [3].
• A progressive and chronic induction of gp130 was observed in cells that appeared to be associated with blood vessels [3].
• Blockade of LIFRbeta inhibited the sweat gland differentiation activity in neuron/gland co-cultures, and extracts of gland-containing footpads stimulated tyrosine phosphorylation of LIFRbeta and gp130 [14].
• We conclude that, by interacting with membrane gp130 and possibly by activating Janus kinase/STAT pathways, IL6RIL6 chimera induces OPCs to differentiate into mature oligodendrocytes, promotes their survival, and could deserve investigation as a therapeutic strategy for enhancing remyelination [15].
• Ribonuclease protection analyses demonstrated the presence of gp130 mRNA in four different nontransformed cell types: hepatocytes, astrocytes, fibroblasts, and endothelial cells [13].

Associations of Il6st with chemical compounds

• Positions 268 and 269 of CNTFRalpha appear to be critical for its interaction with gp130 and LIFRbeta, whereby alanine substitution of the residues at these positions results in antagonism of the CNTF-induced response [1].
• This interaction leads to the association and activation of a second membrane glycoprotein, gp130, which is the IL-6 signal transducing molecule [13].
• The effect of gp130 stimulation on glutamate-induced excitotoxicity in primary hippocampal neurons [16].
• Dexamethasone increases receptor mRNA levels 2.7-fold above controls but has no detectable effect on that of gp130 [17].
• Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1beta [18].

Physical interactions of Il6st

• CONCLUSIONS: Array analysis revealed changes in mRNA levels of several genes not previously associated with activation of the gp130/LIF receptor complex [19].

Regulatory relationships of Il6st

• CONCLUSIONS: These results demonstrate for the first time that a JAK-STAT pathway and a MAPK pathway are present down-stream of gp130 in cardiac myocytes and are rapidly activated by LIF both in vitro and in vivo [20].
• AngII induced phosphorylation of gp130 in the late stage, which was temporally in parallel with the delayed phosphorylation of STAT3 [21].
• In that regard, cardiotrophin-1 (CT-1) activates several signaling pathways via gp130, and induces hypertrophy in neonatal rat cardiomyocytes [22].

Other interactions of Il6st

• Leukemia inhibitory factor receptor and gp130 were expressed in neurons, and the ischemic damage of these proteins was rescued in the high-LIF group [2].
• By contrast, the mRNA and protein levels for CT-1 and the mRNA level for gp130 did not vary in these two models [23].
• A supershift was observed with anti-C/EBP-beta but not with anti-alpha or anti-delta antibodies. mRNA and protein levels of IL-6 and gp130 were detected at low levels in controls, increased at 1 hour of reperfusion, and remained high until 6 hours of reperfusion [9].
• Like primary decidual cells in culture, GG-AD cells express IL-6, IL-6R, and gp130 mRNA [24].
• Thus, GATA-5 may be involved in gp130 signaling in cardiac myocytes [25].

Analytical, diagnostic and therapeutic context of Il6st

• Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that IL-11 and its receptor, CNTF and its receptor, LIFR, and gp130 were constitutively expressed throughout the culture period [26].
• Immunoprecipitation and metabolic labeling experiments demonstrate, in addition to a mature surface expressed gp130, the presence of a major immature form of the molecule within the cell [11].
• We report here the cloning and sequence analysis of the gp130 molecule derived from rat liver [13].
• Molecular cloning and characterization of the rat liver IL-6 signal transducing molecule, gp130 [13].
• The expression of glycoprotein 130 (gp130) was studied in rat primary Sertoli cells by Northern blot analysis [27].

References