INT116950

Context Info Confidence 0.57 First Reported 2004 Last Reported 2011 Negated 1 Speculated 1 Reported most in Body Documents 103 Total Number 104 Disease Relevance 44.48 Pain Relevance 17.53

cytosol (MAPK8) nucleoplasm (MAPK8) mitochondrion (MAPK8) nucleus (MAPK8) response to stress (MAPK8) cytoplasm (MAPK8)

Anatomy Link Frequency fibroblasts 5 pericytes 1 MCF-7 1 cleavage 1 joint 1 MAPK8 (Homo sapiens)

Pain Link Frequency Relevance Heat Kappa opioid receptor 8 100.00 Kinase C 49 99.92 neuralgia 6 99.80 aspirin 29 99.76 Nicotine 480 99.40 antagonist 108 99.34 allodynia 13 99.24 Leflunomide 46 99.20 Inflammatory stimuli 36 98.86 Spinal nerve ligature 20 98.60

Disease Link Frequency Relevance Heat Stress 541 100.00 Metastasis 157 99.92 Toxicity 30 99.82 Breast Cancer 194 99.76 Apoptosis 1267 99.40 Disease 1093 99.32 Neuropathic Pain 34 99.24 Carcinoma 96 99.14 Shock 48 99.12 Colon Cancer 23 98.88

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Finally, a p38 MAPK and a JNK1/2 inhibitor were also used but failed to inhibit SHP mRNA induction by TCA (data not shown).

Negative_regulation (inhibitor) of JNK1

1) Confidence 0.57 Published 2010 Journal Journal of Lipid Research Section Body Doc Link PMC2903791 Disease Relevance 0.06 Pain Relevance 0.03

Selective inhibitors of ERK, p38 MAPK, and JNK suppressed the induction of GRP78, CHOP, and PPAR-beta, attenuated indomethacin-induced cytotoxicity and reduced increased caspase activity.

Negative_regulation (inhibitors) of JNK

2) Confidence 0.45 Published 2007 Journal Eur. J. Pharmacol. Section Abstract Doc Link 17341418 Disease Relevance 0.85 Pain Relevance 0.11

In addition, significant upregulation of VEGF-C mRNA (Figure 7B) and a decreased level of phosphorylated JNK (Figure 7C) were also induced in H157 cells treated with siRNA-podoplanin.

Negative_regulation (decreased) of JNK

3) Confidence 0.42 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2987985 Disease Relevance 0.17 Pain Relevance 0

As a result, significant upregulation of VEGF-C mRNA (Figure 6C) and a decreased level of phosphorylated JNK (Figure 6D) were induced in EBC1-P4 cells treated with siRNA-podoplanin.

Negative_regulation (decreased) of JNK

4) Confidence 0.42 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2987985 Disease Relevance 0.07 Pain Relevance 0

This correlated with inhibition of the downstream target of MEKK1 activity, i.e. the SAPK/JNK kinase.

Negative_regulation (inhibition) of JNK

5) Confidence 0.42 Published 2007 Journal BMC Cancer Section Abstract Doc Link PMC2071920 Disease Relevance 0.05 Pain Relevance 0

Another set of experiments, developed to test the hypothesis that Akt kinase confers resistance to endocrine therapy through suppression of ASK1/JNK pathway, showed that combining RAD001 with letrozole restored activation of the ASK/JNK pathway and increased the sensitivity of MCF-7 cells with constitutively active Akt to endocrine therapy [48].

Negative_regulation (suppression) of JNK in MCF-7

6) Confidence 0.41 Published 2007 Journal Breast Cancer Res Treat Section Body Doc Link PMC2001220 Disease Relevance 0.20 Pain Relevance 0

Consistently, pretreatment with JNK inhibitor SP600125 also decreased JNK activation (Fig. 5B, lane 4).

Negative_regulation (inhibitor) of JNK

7) Confidence 0.39 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2427353 Disease Relevance 0.20 Pain Relevance 0

Furthermore, silencing of JNK expression by siJNKs (24), which efficiently reduced the endogenous JNK protein level (Fig. 5E) but not the control siRNA, decreased H2O2-induced AICD level (Fig. 5E, compare lanes 4 and 6 to lane 2).

Neg (not) Negative_regulation (reduced) of JNK

8) Confidence 0.39 Published 2008 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2427353 Disease Relevance 0.10 Pain Relevance 0

Therefore, we hypothesized that leflunomide may protect from drugs that induce the mitochondrial permeability transition (mPT) by blocking the JNK signaling pathway.

Negative_regulation (blocking) of JNK associated with leflunomide

9) Confidence 0.39 Published 2006 Journal Toxicol. Appl. Pharmacol. Section Abstract Doc Link 16979204 Disease Relevance 0.65 Pain Relevance 0.70

In the absence of JNK inhibition, the response of normal control fibroblasts after oxidative stress amounted to at most 30% apoptotic nuclei at both 250 µM (Figure 16A) and 500 µM (Figure 14) H2O2 by 10 hr after oxidative stress.

Negative_regulation (inhibition) of JNK in fibroblasts associated with stress and apoptosis

10) Confidence 0.34 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 1.70 Pain Relevance 0

Blockade of JNK did not significantly enhance apoptosis in normal control fibroblasts that were not subjected to oxidative stress, confirming the specificity of the JNK effect for the stress state.

Negative_regulation (Blockade) of JNK in fibroblasts associated with stress and apoptosis

11) Confidence 0.34 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 1.45 Pain Relevance 0

Overexpression of Galphat in COS-7 cells clearly suppressed kappa-opioid receptor-stimulated JNK activity, indicating that the pathway is primarily regulated by Gbetagamma.

Negative_regulation (suppressed) of JNK associated with kappa opioid receptor

12) Confidence 0.34 Published 2004 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 14996948 Disease Relevance 0.13 Pain Relevance 0.44

Only the dual inhibitor of p38 and JNK and the use of combined siRNA silencing of p38 and cJun abrogated the ability of NO-aspirin to block cell growth.

Negative_regulation (inhibitor) of JNK associated with aspirin

13) Confidence 0.33 Published 2006 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 16169935 Disease Relevance 0.47 Pain Relevance 0.41

Furthermore, Trolox attenuated indomethacin-induced increased phosphorylation in ERK, p38 MAPK, JNK, and AKT.

Negative_regulation (attenuated) of JNK

14) Confidence 0.32 Published 2007 Journal Eur. J. Pharmacol. Section Abstract Doc Link 17341418 Disease Relevance 0.61 Pain Relevance 0.05

Moreover, the podoplanin-mediated downregulation of the VEGF-C gene via JNK (the podoplanin-JNK-VEGF-C axis) was newly found as one of the possible underlying mechanisms.

Negative_regulation (downregulation) of JNK

15) Confidence 0.31 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2987985 Disease Relevance 1.18 Pain Relevance 0

A decreased level of phosphorylated JNK but not of total JNK was induced by siRNA-mediated podoplanin knockdown (Figures 6D and 7C), suggesting that podoplanin could induce JNK phosphorylation.

Negative_regulation (decreased) of JNK

16) Confidence 0.31 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2987985 Disease Relevance 0.27 Pain Relevance 0.04

Real-time RT-PCR revealed that the VEGF-C gene expression level in EBC1-Ps treated with sp600125, a JNK inhibitor, was significantly improved, nearly to the level found in EBC1-Vs (Figure 6A), whereas no change in the VEGF-C expression was observed in EBC1-Ps treated with the ROCK inhibitor Y-27632 (data not shown).

Negative_regulation (inhibitor) of JNK

17) Confidence 0.31 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2987985 Disease Relevance 0.17 Pain Relevance 0

The body of our findings is that podoplanin in LSCCs can induce VEGF-C downregulation via the JNK signaling pathway(s), and can impair tumor-associated lymphangiogenesis and lymphogenous metastasis

Negative_regulation (downregulation) of JNK in body associated with cancer and metastasis

18) Confidence 0.31 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2987985 Disease Relevance 0.81 Pain Relevance 0

Using either parental NCTC2544 or vector expressing cells (not shown) we found no equivalent inhibition of JNK activity (Panel A) at any concentration of peptide tested.

Negative_regulation (inhibition) of JNK

19) Confidence 0.30 Published 2010 Journal Cellular Signalling Section Body Doc Link PMC2806525 Disease Relevance 0 Pain Relevance 0.08

have not revealed a specific isoform to date responsible for JNK inhibition (not shown).

Negative_regulation (inhibition) of JNK

20) Confidence 0.30 Published 2010 Journal Cellular Signalling Section Body Doc Link PMC2806525 Disease Relevance 0 Pain Relevance 0

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