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Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways. That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3. In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop. Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3. Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism. Has a role in embryonic development. Essential for survival of motor and sensory neurons and for differentiation of astrocytes. Required for expression of TRPA1 in nociceptive neurons. Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation. Required for normal trabecular bone mass and cortical bone composition.
Gene References into Functions
This functional mouse model of PMM2-CDG, in vitro assays and identification of the novel gp130 biomarker all shed light on the human disease, and moreover, provide the essential tools to test potential therapeutics for this untreatable disease.PMID:27053713
Results suggest that the protective role of gp130-dependent STAT3 activation in experimental colitis involves the expansion and activation of mucosal myeloid-derived suppressor cells.PMID:26848037
gp130-mediated adipose tissue lipolysis promotes hepatic steatosis and insulin resistance.PMID:26384383
Deregulation of gp130/STAT3 signalling augments the acute phase reponse and macrophage infiltration during atherosclerosis without impacting on the development of aortic plaques.PMID:25545330
Significant differential expression (both increases and decreases) of multiple IL-6/gp130 cytokines, such as LIF, oncostatin-M, and ciliary neurotrophic factor, occurred after Muller cell ablationPMID:25722214
GP130 signaling collaborated with MYC to induce MM and was responsible and sufficient for directing the plasma cell phenotype.PMID:25384216
gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3PMID:25731159
osteocytic gp130 signaling is required for normal trabecular bone mass and proper cortical bone composition.PMID:24339143
Osteocytic gp130 is required to maintain PTH1R expression in the osteoblast lineage, and for the stimulation of osteoblast differentiation that occurs in response to PTH.PMID:25228504
study concludes that in a setting of islet inflammation and pathophysiology modeling type 2 diabetes, activation of alpha-cell gp130 receptor signaling has deleterious effects on alpha-cell function, promoting hyperglycemia.PMID:24812426
In small sensory neurons, gp130 has an essential role in mechanonociception and in the regulation of transient receptor potential ankyrin (TRPA)1 expression.PMID:25057188
Omega-3 fatty acids do not affect surface or total cell expression of GP130 in isolated mouse splenic CD4 T cells.PMID:24944284
GP130 and STAT3 are critical for uterine receptivity and implantation.PMID:23885093
excessive CXCL1 expression in gp130-deficient endothelial cells augments neutrophil adhesion but hinders migration, most likely by disrupting chemotactic gradientsPMID:24081661
These results reveal that gp130 cytokines (particularly IL-27) are key regulators of CD4+ T cell responses during an established chronic viral infection, empowering both humoral and cytotoxic immunity.PMID:23993651
Il6st gene mRNA and gp130 protein distribution in the brain structures in mice differing in exagerrated freezing reaction (catalepsy)PMID:23888778
Kupffer cells are essential to the viability of liver sinusoidal endothelial cells, which appears to be mediated through glycoprotein 130 expression in sepsis.PMID:23306157
The first study of the role of a relatively new member of the gp130 family, IL-11, in spinal cord injury is presented.PMID:22715999
Analysis of the innate immune response and the regulation of hepatic antibacterial pathways showed that the LPS-triggered hepatocellular response via the Toll-like receptor-4 pathway was regulated differentially by HGF/c-Met and IL-6/gp130.PMID:22986785
An interleukin-6 receptor-dependent molecular switch mediates signal transduction of the IL-27 cytokine subunit p28 (IL-30) via a gp130 protein receptor homodimer.PMID:23209286
Soluble interleukin-6 receptor induces motor stereotypies and co-localizes with gp130 in regions linked to cortico-striato-thalamo-cortical circuitsPMID:22911828
Data unravel a vital function of IL-6/gp130-STAT1/3 signals for BM engraftment and haematopoiesis, as well as for host survival after transplantation.PMID:22745821
These findings indicate a crucial protective function of gp130-expressing neurons in a model of chronic encephalitis.PMID:22640806
Taking into account the gene penetrance, this can indicate effect of the gene i16st on choice of the active ("regulated") or passive ("dependent") way of the organism reacting to temperature actions.PMID:22567975
both LIFR and gp130 protein expression were increased in the sciatic nerve and gastrocnemius muscle of diabetic mice.PMID:21565387
Results point to a role of sgp130 in the blockade of classic signaling and indicate that in vivo only low therapeutic concentrations of sgp130Fc guarantee blockade of IL-6 trans-signaling without affecting IL-6 classic signaling.PMID:21990364
Hyper-interleukin-11 novel designer molecular adjuvant directly targets gp130 leading to induction of specific and long lasting anticancer immune response.PMID:21995459
SOCS3 has an important role in regulation of cardiac gp130 signaling in the pathogenesis of contractile dysfunction and ventricular arrhythmias.PMID:22082679
These data suggest that Muller cell activation of gp130 is not essential for photoreceptor protection.PMID:20238070
Data show that gp130-dependent astrocyte activation is crucial to ameliorate EAE.PMID:21515788
gp130 is expressed in human oocyte but not in mouse.PMID:21079661
Data suggest that NPY, PACAP, galanin, and VIP are regulated by gp130 and may play an important role in cardiac and neuronal remodeling after ischemia-reperfusion.PMID:21035185
It was suggested that a high predisposition to catalepsy in mice can be defined by the Map3k1, Il6st, Gzmk, and Hspb3 genes' coexpression network.PMID:21162133
Result indicates an association between gp130 and hereditary catalepsy, increased functional activity rather than expression of gp130 and the involvement of gp130 in the mechanism of lipopolysaccharide-induced alteration of behavior.PMID:20707873
1) the participation of gp130 in the regulation of TPH2, 5-HT(1A)- and 5-HT(2A)-receptor genes and 2) association of this protein in the genetically determined sensitivity to LPS.PMID:21090245
gp130/STAT3 signaling in hepatocytes provides protection in a cholestatic hepatitis mousePMID:20382701
Ligand-independent constitutively active heterodimers for all known gp130-receptor complexes based on IL-15/IL-15R alpha-sushi fusion proteins, were generated.PMID:20554759
sgp130 may have a beneficial effect during intestinal virus infection by disrupting interleukin-6 trans-signallingPMID:20353422
Impaired downregulation of gp130-mediated STAT3 activation in subacute infarction promotes cardiac inflammation, adverse remodeling, and heart failure, suggesting a potential causative role of high interleukin-6 serum levels after myocardial infarction.PMID:20585009
studies demonstrate that stimulation of enhanced growth of sympathetic neurons after a conditioning lesion is dependent on gp130 cytokine signaling and is blocked in the absence of signaling by these cytokines in spite of an increase in ATF3PMID:20144891
p38, activated by IL-1beta, TNFalpha or environmental stress, impairs IL-6-induced JAK/STAT signalling through phosphorylation of the common cytokine receptor subunit gp130 and its subsequent internalisation and degradation.PMID:20200229
the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.PMID:20348091
Data demonstrate that the gp130/Stat3 axis represents an essential effector of activated Rac1 for the regulation of key cellular functions.PMID:19852956
gp130 activation in photoreceptors had a general protective role independent of whether stress was caused by light or genetic mutationsPMID:19948961
results suggest that the Y759 point mutation in gp130 attenuates the early phase of defense against Listeria infection, possibly owing to insufficient elevation of IFNgamma levels, and thus gp130 is a possible candidate gene for Listeria susceptibilityPMID:12070777
The Role of gp130 in cerebral cortical developmentPMID:12097503
gp130-mediated STAT1/3 activation is needed for the normal balance of hematopoietic progenitors during fetal & adult life. This activation has 2 roles, 1) restricting production of immature progenitors; 2) promoting megakaryocyte maturation.PMID:12423677
its abnormal signaling causes autoimmune diseases--reviewPMID:12518458
gp130 plays an indispensable role in the expansion of hematopoietic precursor cells in the fetal mouse aorta-gonad-mesonephrosPMID:12691915
SOCS3 regulates the plasticity of gp130 signaling.PMID:12754506
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Subcellular Location
Cell membrane; Single-pass type I membrane protein.
Protein Families
Type I cytokine receptor family, Type 2 subfamily
Tissue Specificity
Expression not restricted to IL6-responsive cells. Found in tissues such as brain, heart, thymus, spleen, kidney, lung and liver. Found in all the cell lines tested except BaF-B03. Expressed paraventricular nucleus of the hypothalamus.