Gene interactions and pathways from curated databases and text-mining

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IL6 — JAK2

Pathways - manually collected, often from reviews:

Text-mined interactions from Literome

Wang et al., Oncogene 2000 : PD180970 did not affect MAPK activation by PDGF or the JAK dependent activation of Stat3 by interleukin-6
Iwamoto et al., Oncogene 2000 (Acute-Phase Reaction) : Furthermore, in vitro kinase assay indicated that JAB suppressed hyperactivation of JAK1/JAK2 and JAK1 induced by IFNgamma and IL-6 plus sIL-6R respectively, but not v-Src induced basal JAK1/JAK2 activity
Schieffer et al., Circ Res 2000 : Inhibition of JAK2 by its inhibitor AG490 ( 10 micromol/L ) blocked not only JAK2 activation but also IL-6 synthesis
Song et al., Zhonghua Xue Ye Xue Za Zhi 2000 (Multiple Myeloma) : The biological function of IL-6 on Sko-007 cells is mediated by the activation of Jak/STAT and Ras/NF-IL-6 signal transduction pathways
Kuo et al., Oncogene 2001 : In Hep3B cells, the JAK/STAT3 , ERK, and PI 3-K/Akt pathways were activated by IL-6 stimulation
Song et al., Zhonghua Zhong Liu Za Zhi 2001 (Multiple Myeloma) : ( 1 ) IL-6 could promote the proliferation of U266 cells, ( 2 ) both JAK/STAT and Ras/NF-IL-6 signal transduction pathways were activated by IL-6 in the U266 cells and ( 3 ) Cell proliferation and activation of the two IL-6 signal transduction pathways were inhibited by Forskolin ; down regulating the actiration of these two signal transduction pathways at the same time
Legendre et al., J Biol Chem 2003 : JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes ... In the present study, we show for the first time that interleukin-6 (IL) , in the presence of its soluble receptor ( sIL-6R ), induces activation of JAK1, JAK2 , and STAT1/STAT3 proteins in bovine articular chondrocytes
Okugawa et al., Am J Physiol Cell Physiol 2003 (Gram-Negative Bacterial Infections) : Finally, we show that JAK2 is involved in the production of IL-1beta and IL-6
Fasshauer et al., Biochem Biophys Res Commun 2004 : Studies using pharmacological inhibitors suggested that the positive effects of GH and IL-6 on MCP-1 synthesis are at least in part mediated by janus kinase 2 and p44/42 mitogen activated protein kinase
Fasshauer et al., J Endocrinol 2004 (Insulin Resistance) : Furthermore, stimulation experiments and studies using pharmacologic inhibitors suggested that the positive effect of TNFalpha, GH and IL-6 on SOCS-1 mRNA is, at least in part, mediated by Janus kinase (Jak) 2
Watanabe et al., Am J Nephrol 2004 (Arteriosclerosis) : Rat VSMC were stimulated with IL-6 in the presence or absence of a JAK 2 inhibitor, and the activation of STAT 3 ( by Western ), MCP-1 ( by ELISA ) and DNA synthesis ( by ( 3 ) H-thymidine incorporation ) was determined
Siavash et al., Br J Cancer 2004 (Carcinoma, Squamous Cell...) : Abrogation of IL-6 mediated JAK signalling by the cyclopentenone prostaglandin 15d-PGJ ( 2 ) in oral squamous carcinoma cells ... Importantly, 15d-PGJ ( 2 ) selectively abrogated constitutive and IL-6 mediated JAK phosphorylation without affecting EGFR activated levels ... Our findings provide the first evidence for 15d-PGJ ( 2 ) -mediated downregulation of constitutive and IL-6 induced JAK signalling in cancer and support that JAK inhibition and suppression of EGFR independent Stat3 activation by 15d-PGJ ( 2 ) represent a promising approach for induction of apoptosis in oral SCC cells
To et al., Br J Cancer 2004 (Cell Transformation, Neoplastic...) : The interleukin mediated Janus kinase ( JAK ) /STAT pathway plays a crucial role in carcinogenesis
Dawn et al., Cardiovasc Res 2004 (Myocardial Infarction...) : Myocardial IL-6 protein expression, activation of Janus kinase (JAK) 1 and JAK2 , and signal transducers and activators of transcription ( STAT ) 1 and STAT3 after ischemic PC protocol were examined
Fasshauer et al., J Endocrinol 2004 (Acute-Phase Reaction) : Inhibitor studies suggested that the positive effect of IL-6 on SAA3 expression is at least in part mediated by Janus kinase 2
Kimura et al., Proc Natl Acad Sci U S A 2005 : Suppressor of cytokine signaling-1 selectively inhibits LPS induced IL-6 production by regulating JAK-STAT
Karadag et al., Blood 2006 (MAP Kinase Signaling System...) : Furthermore, inhibitors of p38 MAPK and cPLA2, but not NF-kappaB and JAK2 , signaling pathways inhibited ADAM-9 induced IL-6 production by hOBs ( P < .01 )
Shouda et al., Cancer Lett 2006 (Histiocytoma, Malignant Fibrous) : The JAK2 kinase inhibitor, tyrphostin AG490, suppressed the growth of MFH cells and inhibited the secretion of IL-6
Lee et al., Mol Cancer Ther 2006 (Carcinoma, Squamous Cell...) : We conclude that SOCS-1 methylation status can differentially affect STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and response to pharmacologic antagonists
O'Hara et al., Biochem J 2007 : Inhibition with siRNA ( small interfering RNA ) targeting the SFK Lck, but not dominant negative JAK ( Janus kinase ), prevented Cr ( VI ) -stimulated phosphorylation of both STAT3 isoforms and induction of IL-6
Muto et al., Mol Cancer Ther 2007 (Multiple Myeloma) : Emodin inhibited interleukin-6 induced activation of Janus activated kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 ( STAT3 ), followed by the decreased expression of Mcl-1
Yu et al., Int J Biochem Cell Biol 2008 : SOCS 3 and PPAR-gamma ligands inhibit the expression of IL-6 and TGF-beta1 by regulating JAK2/STAT3 signaling in pancreas
Suh et al., J Cell Physiol 2009 : IL-6 increased Janus Kinase (JAK)-2 , signal transducer and activator of transcription ( STAT ) -3 phosphorylation, intracellular Ca ( 2+ ) concentration, and PKC phosphorylation
Gong et al., Mol Nutr Food Res 2009 (Prostatic Neoplasms) : Moreover, an antioxidant reagent, N-acetyl-L-cysteine (NAC) which suppresses reactive oxygen species ( ROS ) generation, reversed the early inhibitory effects of PEITC on cell proliferation, constitutive or IL-6 mediated JAK-STAT3 phosphorylation in PCa cells
Radtke et al., J Cell Sci 2010 : We show that 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
Tanabe et al., Journal of neuroinflammation 2010 (Glioma) : The Janus family of tyrosine kinase ( JAK ) inhibitor I, an inhibitor of JAK 1, 2 and 3, attenuated TNF-alpha induced phosphorylation of STAT3 and significantly reduced TNF-alpha stimulated IL-6 release
Nakaya et al., Leuk Res 2011 (Multiple Myeloma) : Further, AF inhibited constitutive and IL-6 induced activation of JAK2 and phosphorylation of STAT3 followed by the decreased expression of Mcl-1
Tseng et al., Cytokine 2010 : We conclude that primary human thymic epithelial cells produce GRO-alpha and that its expression is regulated primarily by autocrine IL-6 and IL-6 activated Jak2 signaling
Liu et al., Neurotox Res 2011 : These results suggest that IL-6 protects neurons against NMDA induced apoptosis, and that the IL-6 neuroprotection is jointly mediated by JAK-STAT3 and PI3K-Akt signaling pathways
Huang et al., Molecular cancer 2010 (Adenocarcinoma...) : Our biochemical and genetic studies clearly demonstrated that Jak2/Stat3 , in combination with other IL-6 downstream pathways, contributed frequently and substantially to IL-6 autocrine production in a broad spectrum of cancer cell lines as well as in clinical cancer samples
Ngo et al., Nature 2011 (Burkitt Lymphoma...) : The L265P mutant promoted cell survival by spontaneously assembling a protein complex containing IRAK1 and IRAK4, leading to IRAK4 kinase activity, IRAK1 phosphorylation, NF-?B signalling, JAK kinase activation of STAT3, and secretion of IL-6 , IL-10 and interferon-ß
Tanabe et al., Journal of neuroinflammation 2011 : The IL-1ß stimulated levels of IL-6 were suppressed by wedelolactone ( an inhibitor of I?B kinase ), SP600125 ( an inhibitor of SAPK/JNK ), and JAK inhibitor I ( an inhibitor of JAK 1, 2 and 3 )
Migita et al., J Rheumatol 2011 (Acute-Phase Reaction...) : Our data indicated that CP690,550 blocked IL-6 induced JAK2/STAT3 activation , as well as the induction of A-SAA
Betts et al., Blood 2011 : JAK2 inhibition also reduces the production of IL-6 and TNF-a in allogeneic MLRs, impairing the activation of central and effector memory T cells as well as the expansion of responder Th1 and Th17 cells
Gu et al., Molecular cancer 2011 (Carcinoma, Hepatocellular...) : Then, IL-6 in turn activated JAK2/STAT3 signaling and subsequently up-regulated its downstream targets IL-8, MMP2, and VEGF
Ge et al., Prostate 2012 (Prostatic Neoplasms) : IL-6 activated JAK2 and STAT3 pathways in LNCaP-C3 cells but not in LNCaP-S17 cells
Yang et al., Cancer Biol Ther 2012 (Neuroblastoma) : Sorafenib inhibits endogenous and IL-6/S1P induced JAK2-STAT3 signaling in human neuroblastoma, associated with growth suppression and apoptosis
Dittrich et al., Molecular bioSystems 2012 : Misregulated interleukin-6 (IL-6) induced Jak/STAT signaling contributes to many diseases
Nam et al., J Pept Sci 2012 : Inhibition of JAK ( STAT1/STAT5 kinase ) with AG490 markedly reduced the production of IL-6 and TNF-a in macrophages
Tian et al., PloS one 2012 (Melanoma) : Accordingly, SOID-8 inhibited IL-6 induced activation of STAT3 and JAK2 in melanoma cells
Soth et al., J Med Chem 2013 : Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1 dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2 dependent IL-6 stimulated pathway
Russell et al., Islets 2013 : Differential effects of interleukin-13 and interleukin-6 on Jak/STAT signaling and cell viability in pancreatic ß-cells
Andrés et al., Exp Dermatol 2013 (MAP Kinase Signaling System...) : Tyr705 phosphorylation was induced by IL-6 and IL-20 in a Jak2 dependent manner, and moreover, phosphorylation of Tyr705 produced a strong increase in STAT3 transcriptional activity
Muraoka et al., Clin Exp Rheumatol 2013 (Arthritis, Rheumatoid) : Effects of inhibitors of janus kinase 2 (JAK2) , phosphatidylinositol 3-kinase (PI3K), and mitogen activated protein kinase ( MAPK ) on IL-6 production were evaluated
Fang et al., PloS one 2013 : Further investigation of the underlying mechanism revealed simvastatin could exert the anti-tumor effects by suppressing IL-6 induced phosphorylation of JAK2 and STAT3
Lai et al., PloS one 2013 : Additionally, IL-6 mediated angiotensinogen expression through the Janus kinase ( JAK ) /signal transducer and activator of transcription 3 ( STAT3 ) and JAK/p38 signaling ... IL-6 mediated signaling, JAK2 , STAT3 and p38 inhibitors reduced angiotensinogen expression in the partially hepatectomized mice
King et al., Endocrinology 1995 : Dexamethasone does not inhibit induction of tyrosyl phosphorylation of ERK proteins by epidermal growth factor or phorbol myristate acetate, nor does it block induction of tyrosyl phosphorylation of Stat3/APRF by leukemia inhibitory factor or interleukin-6 , or induction of JAK2 by leukemia inhibitory factor or interferon-gamma
Xu et al., J Clin Invest 1995 (Cell Transformation, Viral) : Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6
Berger et al., Blood 1997 (Multiple Myeloma) : Prior treatment of U266 cells with IFN-beta downregulated IL-6 induced tyrosine phosphorylation of gp130, Jak2 , PTP1D/Syp, Shc, and Erk2, and GTP loading of p21ras
Faris et al., Immunology 1997 : We have previously shown that IL-6 induces activation of JAK1 and JAK2 in human B cell lines
Leven et al., Blood Cells Mol Dis 1997 : Studies on protein phosphorylation revealed that IL6 , but not TPO, stimulated phosphorylation of JAK1, JAK2 and MAP kinase ... Studies on protein phosphorylation revealed that IL6 , but not TPO, stimulated phosphorylation of JAK1, JAK2 and MAP kinase
Sengupta et al., Proc Natl Acad Sci U S A 1998 : These results demonstrate an ERK mediated mechanism for inhibiting IL-6 induced Jak-STAT signaling that is rapid and inducible, and thus differs from previously described mechanisms for downmodulation of the Jak-STAT pathway