Ignet

Gene Information

Gene symbol: STAT3

Gene name: signal transducer and activator of transcription 3 (acute-phase response factor)

HGNC ID: 11364

Synonyms: APRF

Related Genes

#	Gene Symbol	Number of hits
1	AATF	1 hits
2	ADIPOQ	1 hits
3	AGT	1 hits
4	ANG	1 hits
5	ANPEP	1 hits
6	ATHS	1 hits
7	BBS2	1 hits
8	BCL2L1	1 hits
9	CD40	1 hits
10	CISH	1 hits
11	CNTF	1 hits
12	COL1A1	1 hits
13	COL4A4	1 hits
14	CRP	1 hits
15	EGFR	1 hits
16	EPHB2	1 hits
17	FASN	1 hits
18	FGF21	1 hits
19	FOXM1	1 hits
20	FOXO1	1 hits
21	G6PC	1 hits
22	GSK3B	1 hits
23	HSP90AA1	1 hits
24	HTR2B	1 hits
25	IL10	1 hits
26	IL17A	1 hits
27	IL6	1 hits
28	INS	1 hits
29	INSR	1 hits
30	IRS2	1 hits
31	JAK2	1 hits
32	LEP	1 hits
33	LEPR	1 hits
34	MAPK1	1 hits
35	MKKS	1 hits
36	MMP7	1 hits
37	NOX1	1 hits
38	NOX4	1 hits
39	NOX5	1 hits
40	PCK1	1 hits
41	POMC	1 hits
42	PPARA	1 hits
43	PRKAA1	1 hits
44	PTPN11	1 hits
45	RAC1	1 hits
46	SLC38A2	1 hits
47	SOCS1	1 hits
48	SOCS3	1 hits
49	SPP1	1 hits
50	STAT1	1 hits
51	TNF	1 hits
52	VEGFA	1 hits

Related Sentences

#	PMID	Sentence
1	10799542	By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling; Tyr(985) controls the tyrosine phosphorylation of SHP-2, and Tyr(1138) controls STAT3 activation.
2	10799542	Tyr(985)-mediated recruitment of SHP-2 does not alter tyrosine phosphorylation of Jak2 or STAT3 but results in GRB-2 binding to tyrosine-phosphorylated SHP-2 and is required for the majority of ERK activation during LRb signaling.
3	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.
4	11018044	Phosphorylated Tyr(1138) binds STAT3 to mediate its tyrosine phosphorylation and transcriptional activation, while phosphorylated Tyr(985) binds the tyrosine phosphatase SHP-2 and reportedly mediates both activation of ERK kinases and inhibition of LRb-mediated STAT3 activation.
5	11416024	Immunoblot analysis of hypothalamic lysates with a phospho-specific STAT3 antibody showed a 6- to 7-fold stimulation of STAT3 tyrosine phosphorylation in response to both leptin and TNFalpha.
6	11416024	In contrast to its action in the brain, leptin was unable to produce STAT3 phosphorylation in the liver, either alone or in combination with TNFalpha.
7	11416024	These data show that TNFalpha, independently of leptin, activates hypothalamic STAT signaling pathways and enhances leptin action at the level of STAT3.
8	11967010	We found that Ang II-induced JAK2, STAT1, STAT3, STAT5A/B and SHP-2 phosphorylations were enhanced by HG, whereas that of SHP-1 was reduced.
9	12424252	Moreover, we demonstrated that CNTF can activate STAT 3 in adipose tissue and skeletal muscle in vivo.
10	12921973	Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats.
11	15240880	In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity.
12	15601754	Treatment of rat VSMCs with 5-HT (10(-6) M) resulted in time-dependent activation ( approximately 2-fold) of JAK2, JAK1, and STAT1, but not STAT3 (maximal at 5 min, returned to baseline by 30 min).
13	15601754	Treatment of streptozotocin-induced diabetic rats with ketanserin (5 mg.kg-1.day-1) reduced activation of JAK2 and STAT1 but not STAT3 in endothelium-denuded thoracic aorta in vivo. 5-HT (10(-6) M) treatment resulted in increased cell proliferation and increased DNA synthesis, which were inhibited by the JAK2 inhibitor AG490.
14	15749807	Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone.
15	15749807	Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels.
16	15913829	In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity.
17	16026757	The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor.
18	16289036	In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation.
19	16306356	Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 beta-cells.
20	16721034	However, DEX reduced leptin-induced STAT3 phosphorylation in the cortex and hypothalamus, and it increased AMP-activated protein kinase (AMPK) phosphorylation only in the hypothalamus.
21	16876574	Leptin activates Janus-activating kinase2 (Jak2) and STAT 3, resulting in stimulation of anorexigenic peptides, e.g., alpha-MSH and CART, and inhibition of orexigenic peptides, e.g., NPY and AGRP.
22	17023536	Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese.
23	17023536	We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription.
24	17023536	These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response.
25	17063460	While the early actions of FGF-21 on 3T3-L1 adipocytes involve rapid accumulation of intracellular calcium and phosphorylation of Akt, GSK-3, p70(S6K), SHP-2, MEK1/2, and Stat3, continuous treatment for 72 h induces an increase in PPARgamma protein expression.
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	18171429	In order to understand leptin action we have explored the physiological function of LRb signalling pathways, defining important roles for signal transducer and activator of transcription-3 (STAT3) in positive signalling and for LRbTyr(985)-mediated feedback inhibition in leptin signal attenuation.
28	18178618	Up-regulation of cyclin D1 and D2 by ICA512-CCF is affected by knockdown of STAT3 and STAT5, respectively, whereas it does not require insulin signaling.
29	18268048	The aim of our study was to examine the role of the signal transducers and activators of transcription 3 (STAT3) in insulin signaling.
30	18268048	These data indicate that STAT3 sensitizes insulin signaling by negatively regulating GSK-3beta.
31	18268048	Inactivation of STAT3 in the liver contributes significantly to the pathogenesis of insulin resistance.
32	19258740	Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase.
33	19258740	The hepatic abundance of mRNAs for fatty acid synthase and acetyl-CoA carboxylase, both of which catalyze the synthesis of fatty acids, was increased by overexpression of STAT3, whereas that of mRNAs for sterol regulatory element-binding proteins 1a, 1c, or 2 was unaffected.
34	19066310	Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase).
35	19205029	Indeed, pioglitazone prevented aberrant increases in signal transducers and activators of transcription (STAT)3 phosphorylation and suppressor of cytokine signaling (SOCS)-3 mRNA in the liver in KK-A(y) mice.
36	19661066	This study revealed a novel role of ERK in Th17 differentiation through down-regulation of STAT3 phosphorylation and RORgamma t expression.
37	19741197	In cells transfected with small interfering RNA (siRNA) targeting STAT3, the RNA and protein expression of SNAT2, but not SNAT1, was reduced and the stimulating effect of IL-6 on system A activity was abolished.
38	19875458	Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells.
39	19875458	Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect.
40	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.
41	19875458	In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling.
42	18378570	Prior studies have implicated oxidative stress and NADPH oxidase-mediated activation of signal transducer and activator of transcription 3 (STAT3) in diabetes-induced increases in expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1 and breakdown of the blood-retinal barrier (BRB).
43	19911006	We show that AATF is induced by ER stress through the PERK-eIF2alpha pathway and transcriptionally activates the v-akt murine thymoma viral oncogene homolog 1 (AKT1) gene through signal transducer and activator of transcription 3 (Stat3), which sustains Akt1 activation and promotes cell survival.
44	20652679	The intracellular signalling pathway mediating the effect of AMPK on IL-6-stimulated acute-phase marker expression was characterised by assessing the phosphorylation levels of the candidate protein signal transducer and activator of transcription 3 (STAT3) in response to AMPK agonists.
45	20652679	For the first time we show that AMPK appears to regulate IL-6 signalling by directly inhibiting the activation of the main downstream target of IL-6, STAT3.
46	20846165	Adenoviral delivery of an IL-10 receptor construct to the cells restored IL-10 responsiveness as assessed by signal transducer and activator of transcription-3 (STAT-3) phosphorylation.
47	21103795	IL-17 could activate Src/PI3K, MAPK, Stat3, and PKC, resulting in carcinogenesis.
48	21056997	Leptin receptor-free tumor cells display reduced STAT3 tyrosine phosphorylation on residue Y705 but have increased serine phosphorylation on residue S727, consistent with preserved mitochondrial function in the absence of the leptin receptor.
49	20870968	Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ?50 and ?20 ng/ml, respectively.
50	20870968	The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor.
51	20978825	In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues.
52	20978825	Phosphorylated STAT3 then activates CRP gene transcription.
53	20978825	CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot.
54	20978825	Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues.
55	20978825	Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway.
56	21459325	We show here that adiponectin upregulates IRS-2 through activation of signal transducer and activator of transcription-3 (STAT3).
57	16449352	We found that pretreatment with simvastatin significantly inhibited HG- and ANG II-induced collagen IV production, JAK2 activation, and phosphorylation of STAT1 and STAT3 in GMC.
58	20068134	Upregulation of Socs3 in POMC neurons leads to impairment of STAT3 and mammalian target of rapamycin (mTOR)-S6K-S6 signaling, with subsequent leptin resistance, obesity, and glucose intolerance.
59	20068134	Unexpectedly, Socs3 upregulation in leptin receptor neurons results in increased expression of STAT3 protein in mutant hypothalami, but does not lead to obesity.
60	20185635	SOCS gene delivery also decreased the activation of STAT1 and STAT3 and the expression of proinflammatory and profibrotic proteins in the diabetic kidney.
61	21481787	Using a Kras-driven mouse model of PDA, we establish that the inflammatory mediator Stat3 is a critical component of spontaneous and pancreatitis-accelerated PDA precursor formation and supports cell proliferation, metaplasia-associated inflammation, and MMP7 expression during neoplastic development.
62	20332345	Moreover, inhibition of Nox4 attenuated hypoxia-induced upregulation of HIF-1alpha and high-glucose-elicited phosphorylation of STAT3.
63	21602511	Treatment with MEDICA analog resulted in total body sensitization to insulin, suppression of lipopolysaccharide-induced hCRP and interleukin-6-induced acute phase reactants and robust decrease in FoxO1 transcriptional activity and in coactivation of STAT3.
64	21617181	It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3).
65	21617181	Moreover, GW501516 prevented IL-6-dependent induction of extracellular signal-related kinase (ERK)1/2, a serine-threonine-protein kinase involved in serine STAT3 phosphorylation.
66	21617181	Several steps in STAT3 activation require its association with heat shock protein 90 (Hsp90), which was prevented by GW501516 as revealed in immunoprecipitation studies.
67	21298325	The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction.
68	21298325	However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus.
69	21298325	Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription.
70	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.
71	16226915	This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins.
72	16226915	Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins.
73	16226915	These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver.
74	21267512	Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice.
75	21633715	Eleven inflammation- and microvascular-related genes previously demonstrated to be upregulated in young diabetic rats (complement component 1 s subcomponent [C1s], chitinase 3-like 1 [Chi3L1], endothelin 2 [Edn2], guanylate nucleotide binding protein 2 [Gbp2], glial fibrillary acidic protein [Gfap], intracellular adhesion molecule 1 [Icam1], janus kinase 3 [Jak3], lipopolysaccharide-induced TNF factor [Litaf], complement 1-inhibitor [Serping1], signal transducer and activator of transcription 3 [Stat3], tumor necrosis factor receptor subfamily member 12a [Tnfrsf12a]) demonstrated progressively increasing retinal expression in aged normoglycemic rats.
76	20107108	Moreover, we report OPN as a novel negative regulator for the activation of hepatic signal transducer and activator of transcription 3 (STAT3), which is essential for glucose homeostasis and insulin sensitivity.
77	16123338	Basal and insulin-stimulated glucose uptake in heart was significantly reduced in the MHC-PPARalpha mice, and cardiac insulin resistance was mostly attributed to defects in insulin-stimulated activities of insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase, Akt, and tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3).
78	16123338	Overall, these findings indicate that increased activity of PPARalpha, as occurs in the diabetic heart, leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, subsequently leading to reduced cardiac function.
79	21747171	ER activation inhibited ? cell lipid synthesis by suppressing the expression (and activity) of fatty acid synthase via a nonclassical pathway dependent on activated Stat3.
80	18096691	Leptin binding to its receptor triggers multiple signaling pathways, including signal transducer and activator of transcription 3 (Stat 3), phosphatidylinositol-3-kinase, and ERK.
81	20484139	The reduced hepatic glucose output coincided with decreased expression of the gluconeogenic genes G6pc and Pck1 and enhanced hepatic STAT3 phosphorylation and PI3K/Akt signaling in the fasted state.
82	21912612	Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2), reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3) and endothelial nitric oxide synthase (eNOS) but increased IL-6 and TNF-? (all P<0.05 vs.
83	21912612	ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats.
84	18997673	In vitro, Q223R did not affect leptin signaling as reflected by activation of STAT3.
85	21733838	Supported with the facts that Rac1 binds and activates STAT3, which are significantly upregulated in inflammatory bowel disease (IBD) as well as CAC, but 8-hydroxydeoxyguanosine (8-oxo-7,8-dihydrodeoxyguanosine or 8-OHdG) paradoxically can block Rac1 activation and subsequent NADPH oxidase (NOX) inactivation in various inflammation models, we hypothesized that attenuated Rac1-STAT3 and COX-NF-?B pathway by exogenous 8-OHdG administration may ameliorate inflammatory signaling in dextran sodium sulfate (DSS)-induced colitis and can prevent CAC.
86	17192474	The GSK3beta mediators, P-Akt, P-extracellular signal-related kinase (ERK)1, and P-signal transducer and activator of transcription (STAT)3, were also significantly reduced in untreated DBR compared with NDBR rats.
87	21822824	Mechanisms that link these two processes are not completely understood, but transcription factors of the NF-?B family and signal transducer and activator of transcription 3 (STAT3), cytokines such as IL-6 and IL-1? and ligands of the epidermal growth factor receptor (EGFR) family are clearly pivotal players.
88	19150989	In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice.