Ignet

Gene Information

Gene symbol: SOCS3

Gene name: suppressor of cytokine signaling 3

HGNC ID: 19391

Synonyms: SSI-3, CIS3, SOCS-3, Cish3

Related Genes

#	Gene Symbol	Number of hits
1	ADIPOQ	1 hits
2	AKT1	1 hits
3	APOB	1 hits
4	BCL2L1	1 hits
5	CASP3	1 hits
6	CDK9	1 hits
7	CISH	1 hits
8	CNTF	1 hits
9	GSTP1	1 hits
10	HBB	1 hits
11	IFNA1	1 hits
12	IFNG	1 hits
13	IGF1R	1 hits
14	IL1B	1 hits
15	IL4	1 hits
16	IL6	1 hits
17	INS	1 hits
18	INSR	1 hits
19	IRS1	1 hits
20	JAK2	1 hits
21	LBP	1 hits
22	LEP	1 hits
23	MAP3K7	1 hits
24	MAPK1	1 hits
25	MAPK8	1 hits
26	NFE2L2	1 hits
27	NFKB1	1 hits
28	NOS2A	1 hits
29	NPY	1 hits
30	NQO1	1 hits
31	NR1H3	1 hits
32	OSM	1 hits
33	PIK3CA	1 hits
34	PIK3R1	1 hits
35	PPP1R13B	1 hits
36	PRL	1 hits
37	PTGS2	1 hits
38	RPS27A	1 hits
39	SREBF1	1 hits
40	STAT3	1 hits
41	STAT5A	1 hits
42	STAT5B	1 hits
43	TNF	1 hits
44	TRAF6	1 hits

Related Sentences

#	PMID	Sentence
1	10799542	We furthermore investigated the mechanisms by which LRb controls downstream ERK activation and c-fos and SOCS3 message accumulation.
2	10799542	Thus, the two LRb tyrosine residues that are phosphorylated during receptor activation mediate distinct signaling pathways as follows: SHP-2 binding to Tyr(985) positively regulates the ERK --> c-fos pathway, and STAT3 binding to Tyr(1138) mediates the inhibitory SOCS3 pathway.
3	11149898	Expression of a candidate leptin resistance factor, suppressor of cytokine signaling 3 (SOCS-3), was compared in the hypothalamus and white adipocytes of young and old rats before and after induction of hyperleptinemia; hypothalamic SOCS-3 mRNA was approximately 3x higher in old rats before, whereas it was 3x higher in WAT after, hyperleptinemia.
4	12228220	We show that SOCS1 or SOCS3 targeted IRS1 and IRS2, two critical signaling molecules for insulin action, for ubiquitin-mediated degradation.
5	12228220	SOCS1 or SOCS3 bound both recombinant and endogenous IRS1 and IRS2 and promoted their ubiquitination and subsequent degradation in multiple cell types.
6	12560330	IL-6 induced SOCS-3 transcript at 30 min with a maximum effect at 1 h.
7	12560330	SOCS-3 induction by IL-6 paralleled IL-6-dependent inhibition of IR signal transduction.
8	12560330	Ectopically expressed SOCS-3 associated with the IR and suppressed insulin-dependent receptor autophosphorylation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, and activation of Akt.
9	12560330	SOCS-3 was also a direct inhibitor of insulin receptor autophosphorylation in vitro.
10	12560330	In mice exposed to IL-6 for 60-90 min, hepatic SOCS-3 expression was increased.
11	15143188	Mutation of Tyr(570) does not alter the ability of SOCS3 to bind or inhibit Jak2, however.
12	16289036	In vitro experiments demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression and STAT5 activation.
13	16289036	Our results suggest that, in vivo, PRL stimulates SOCS3 expression in stromal adipocytes, independently of STAT5a stimulation.
14	16289036	In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation.
15	16306356	Transcriptional activation of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced STAT3 and STAT5b DNA binding to specific promoter regions.
16	16306356	These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic beta-cells.
17	16389635	Finally, by inducing the expression of the regulatory protein SOCS-3, angiotensin II may impose a late control on the insulin signal.
18	16505233	In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake.
19	16505233	Moreover, SOCS3 is required for tumor necrosis factor-alpha full inhibition of insulin-stimulated IRS-1 and -2 phosphorylation, phosphatidylinositol 3 kinase activity, and glucose uptake.
20	16505233	Whether SOCS3 also inhibits adipocyte insulin signaling in vivo and whether this action further affects systemic insulin sensitivity is not clear.
21	16505233	Overexpression of SOCS3 in adipocytes decreases IRS1 protein levels and subsequent insulin-stimulated IRS-1 and -2 phosphorylation, decreases p85 binding to IRS-1, and leads to decreased insulin-stimulated glucose uptake in adipocytes.
22	17505151	Suppressor of cytokine-3 (SOCS-3) has been proposed as a possible mediator of insulin-induced leptin resistance.
23	17505151	In summary, hyperinsulinemia can induce leptin resistance in L6 myoblasts and this may be mediated via a SOCS-3-dependent mechanism.
24	17513737	SOCS-3/IL-4 receptor complexes, however, were increased in db/db mouse macrophages compared with db/+ mice macrophages as was db/db mouse macrophage SOCS-3 expression.
25	17513737	These results indicate that in the db/db mouse model of T2D, macrophage expression of SOCS-3 is increased, and impaired IL-4-dependent IRS-2/PI3K formation induces a state of IL-4 resistance that disrupts IL-4-dependent production of IL-1RA.
26	17562326	The islets from cKO mice demonstrated hyperactivation of STAT3 and higher induction of Bcl-xL than did islets from WT mice, and SOCS3-deficient beta-cells were more resistant to apoptosis induced by STZ in vitro than were WT beta-cells.
27	18648765	Neither glucose-stimulated insulin release, insulin content or glucose oxidation were affected by SOCS3.
28	18648765	SOCS3 inhibits IL-1-induced signalling through the nuclear factor-kappaB and MAPK pathways and apoptosis induced by cytokines in primary beta cells.
29	18796617	Three mechanisms seem to operate in IL-6-induced insulin resistance: activation of c-Jun NH(2)-terminal kinase 1/2 (JNK1/2), accumulation of suppressor of cytokine signaling 3 (socs3) mRNA, and an increase in PTP1B activity.
30	18796617	When using a pharmacological approach, liver X receptor agonists overcome IL-6-induced insulin resistance by producing downregulation of socs3 and ptp1b gene expression.
31	19008912	Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling.
32	19284081	Leptin, adiponectin, TNF alfa, the hepatic expression of suppressor of cytokine signalling 3 (SOCS3), and hyperinsulinemia have been considered as heavily influencing fibrosis extension and nonresponsiveness to the IFN-alpha.
33	19284081	The adipokines increased hepatic expression of SOCS3, and hyperinsulinemia has been proposed as heavily influencing non-responsiveness to the IFN-alpha and fibrosis extension by maintaining the hepatic stellate cells activated phenotype in patients with chronic hepatitis C and insulin resistance-related obesity.
34	19118408	Compared to NGT group, interleukin-6, tumor necrosis factor-alpha (TNF-alpha), p(22)Phox NADPH oxidase, and thioredoxin interacting protein (TXNIP) mRNA levels were higher and suppressor of cytokine signaling (SOCS-3) mRNA was lower in subjects with IGT and diabetes.
35	19755625	The novel changes described after the HFHC meal elucidate further the mechanisms underlying postprandial inflammation and also provide the first evidence explaining the pathogenesis of insulin and leptin resistance mediated by SOCS-3 after such meals.
36	19875458	Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin.
37	20651008	Increased suppressor of cytokine signaling (SOCS) 3 expression negated IL-6 and OSM effects and significantly reduced cellular apoB mRNA abundance.
38	20683642	The results showed that 100�nM insulin could induce SOCS3 mRNA expression but not protein expression, and overexpression of SOCS3 decreased IRS1 protein level, insulin-stimulated IRS1 tyrosine phosphorylation, PI3K activation, and Akt phosphorylation, but increased IRS1 serine phosphorylation in porcine primary adipocytes.
39	20683642	These results indicate that SOCS3 is an important negative regulator of insulin signaling in porcine adipocytes.
40	20813836	In this report, we show that phenylmethimazole (C10) blocks basal IL6 and leptin production as well as basal Socs-3 expression in fully differentiated 3T3L1 cells (3T3L1 adipocytes) without affecting insulin-stimulated AKT signaling.
41	21249428	While SOCS-3 mRNA levels increased, plasma TNF? and IL-6 levels were also significantly higher in patients with type 2 diabetes. miR-146a expression was negatively correlated to glycated hemoglobin, insulin resistance, TRAF6, and NF?B mRNA levels and circulatory levels of TNF? and IL-6.
42	20068134	Hypothalamic leptin resistance is found in most common forms of obesity, such as diet-induced obesity, and is associated with increased expression of suppressor of cytokine signaling 3 (Socs3) in the hypothalamus of diet-induced obese animals.
43	20068134	This study aims to determine the functional consequence of Socs3 upregulation on leptin signaling and obesity, and to investigate whether Socs3 upregulation affects energy balance in a cell type-specific way.
44	20068134	Unexpectedly, Socs3 upregulation in leptin receptor neurons results in increased expression of STAT3 protein in mutant hypothalami, but does not lead to obesity.
45	20068134	Our study establishes that Socs3 upregulation alone in POMC neurons is sufficient to cause leptin resistance and obesity.
46	20068134	Our study indicates that POMC neurons are important mediators of Socs3's effect on leptin resistance and obesity, but that other cell types or alteration of other signaling regulators could contribute to the development of obesity.
47	21400856	These inflammatory mediators inhibit insulin signaling with several mechanisms, such as serine-phosphorylation of IRS-1, the induction of SOCS3 and the activation of JNK or NFkappaB signaling in insulin-target tissues.
48	20067961	Indexes of inflammation including nuclear factor-kappaB (NF-kappaB) binding, and the expression of SOCS3, tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-1beta in MNCs, increased significantly after glucose and cream intake, but TLR-4 expression and plasma LPS concentrations increased only after cream intake.
49	20067961	Although both glucose and cream induce NF-kappaB binding and an increase in the expression of SOCS3, TNF-alpha, and IL-1beta in MNCs, only cream caused an increase in LPS concentration and TLR-4 expression.
50	21289251	Indices of oxidative stress, inflammation, Nrf-2 binding activity, the concentrations of endotoxin (lipopolysaccharide) and lipoprotein binding protein (LBP), and the expression of toll-like receptor 4 (TLR-4), CD14, IL-1?, TNF?, SOCS-3, Keap-1, NAD(P)H:quinone oxidoreductase-1 (NQO-1), and GST-P1 were measured.
51	21289251	The intake of the supplement suppressed the meal-induced elevations of plasma endotoxin and LBP concentrations, the expression of p47(phox), TLR-4, CD14, SOCS-3, IL-1?, and Keap-1, while enhancing Nrf-2 binding activity and the expression of NQO-1 and GST-P1 genes.
52	21289251	A supplement containing resveratrol and muscadine polyphenols suppresses the increase in oxidative stress, lipopolysaccharide and LBP concentrations, and expression of TLR-4, CD14, IL-1? and SOCS-3 in mononuclear cells after an HFHC meal.
53	20415688	Morphometric studies on arcuate nucleus (ARC) and determinations of circulating parameters and hypothalamic levels of neuropeptide Y (NPY), proopiomelanocortin (POMC), long-form leptin receptor (ObRb), insulin receptor (InsR) and suppressor of cytokine signalling-3 (SOCS-3) mRNA were performed.
54	20415688	Under fed conditions, CR animals presented lower circulating leptin and ghrelin levels (decreases of 37 and 43% in males, and 15 and 34% in females respectively); furthermore, hypothalamic POMC, NPY (only in females), ObRb and InsR mRNA levels were reduced (39, 16 and 26% in males, and 112, 33, 61 and 56% in females), and those of SOCS-3 were increased (86% in males and 74% in females).
55	21599458	Retinal histology was examined and quantified using light microscopy; Apoptosis of retinal neural cells was determined by terminal dUTP nick-end labeling assay; Retinal ultrastructure was examined by transmission electron microscopy; Proteins levels of cleaved caspase-3, signal transduction and activators of transcription-3 (STAT3), phospho-STAT3 (p-STAT3), and suppressors of cytokine signaling 3 (SOCS3) in the retinal tissues were also determined by western blotting.
56	16226915	Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1.
57	16226915	Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3.
58	11078456	To comparatively assess the roles of CNTF and leptin in reversing the starvation-induced changes of hypothalamic neuropeptides and endocrine function and in inducing expression of hypothalamic inhibitors of leptin and CNTF signaling (suppressor of cytokine signaling 3 [SOCS-3]) and mediators of energy expenditure (cyclo-oxygenase 2 [COX-2]), we studied the effect of CNTF and leptin administered by intraperitoneal injections (1 microg/g twice daily) in C57Bl/6J mice fasted for 48 h.
59	11078456	Both leptin and CNTF administration in fasted mice resulted in an induction of SOCS-3 mRNA expression.
60	21519329	OSM in turn attenuated insulin-dependent Akt activation and, as a downstream target, glucokinase induction in hepatocytes, most likely by inducing suppressor of cytokine signaling 3 (SOCS3).
61	21873554	The improvement of insulin resistance is associated with decreased expression of Socs3 and induction of adiponectin.
62	11593036	Suppressor of cytokine signaling 3 (SOCS-3) is a negative feedback regulator of IFN-gamma signaling, shown up-regulated in mouse bone marrow cells by the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma.
63	11593036	Using a doxycycline-inducible SOCS-3 expression system in the rat beta-cell line INS-1, we demonstrate that the toxic effect of both IL-1beta or IFN-gamma at concentrations that reduced the viability by 50% over 3 days, was fully preventable when SOCS-3 expression was turned on in the cells.
64	11593036	Whereas SOCS-3-mediated inhibition of IFN-gamma signaling is described in other cell systems, SOCS-3 mediated inhibition of IL-1beta signaling has not previously been described.
65	11593036	In addition we show that SOCS-3 prevention of IL-1beta-induced toxicity is accompanied by inhibited transcription of the inducible nitric oxide synthase (iNOS) by 80%, resulting in 60% decreased formation of the toxic nitric oxide (NO).
66	16543409	We show here that SOCS-3 inhibits NFkappaB-dependent transcription induced by overexpression of the upstream IL-1 signaling molecules MyD88, IL-1R-activated kinase 1, TNF receptor-associated factor (TRAF)6, and TGFbeta-activated kinase (TAK)1, but not when the MAP3K MAPK/ERK kinase kinase-1 is used instead of TAK1, indicating that the target for SOCS-3 is the TRAF6/TAK1 signaling complex.
67	16543409	By coimmunoprecipitation, it was shown that SOCS-3 inhibited the association between TRAF6 and TAK1 and that SOCS-3 coimmunoprecipitated with TAK1 and TRAF6.
68	16543409	Furthermore, SOCS-3 inhibited the IL-1-induced catalytic activity of TAK1.
69	16543409	Because ubiquitination of TRAF6 is required for activation of TAK1, we analyzed the role of SOCS-3 on TRAF6 ubiquitination and found that SOCS-3 inhibited ubiquitin modification of TRAF6.
70	16543409	These results indicate that SOCS-3 inhibits IL-1 signal transduction by inhibiting ubiquitination of TRAF6, thus preventing association and activation of TAK1.
71	17223256	In summary, leptin induced SOCS-3 expression and its association with the insulin receptor in rat skeletal muscle cells but functional significance of this increase was not apparent upon measuring glucose uptake.