INT104121

Context Info Confidence 0.61 First Reported 2002 Last Reported 2010 Negated 0 Speculated 0 Reported most in Abstract Documents 8 Total Number 8 Disease Relevance 4.84 Pain Relevance 1.41

mitochondrion (MAP2K1) Golgi apparatus (MAP2K1) cytoplasm (MAP2K1) cytosol (MAP2K1) signal transduction (MAP2K1) mitosis (MAP2K1)

Anatomy Link Frequency colon 1 neurons 1 epithelial cells 1 MAP2K1 (Homo sapiens)

Pain Link Frequency Relevance Heat alcohol 10 98.98 COX-2 inhibitor 2 94.24 cINOD 14 92.56 Inflammation 6 81.68 cytokine 4 80.64 dopamine receptor 2 70.44 gABA 3 67.04 Clonidine 1 58.48 agonist 1 56.96 Morphine 1 55.24

Disease Link Frequency Relevance Heat Colon Cancer 16 98.84 Stress 12 98.76 Apoptosis 42 98.40 Death 24 92.92 Cancer 34 89.84 Shock 6 83.44 INFLAMMATION 14 81.68 Polyps 2 76.56 Breast Cancer 28 73.64 Aids-related Complex 1 44.76

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Key:

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Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

HT29-MEK1(R4F) clones displayed a 10- to 20-fold increase in MEK1 activity compared with control HT29-pCEP4 clones.

Positive_regulation (increase) of MEK1

1) Confidence 0.61 Published 2004 Journal Cancer Res. Section Abstract Doc Link 15548677 Disease Relevance 1.19 Pain Relevance 0.13

To determine whether inhibition of MEK/ERK activity is necessary for sulindac-induced apoptosis of human colon cancer cells, stable transfectants were created that express an activated MEK1 gene in HT29 cells.

Positive_regulation (activated) of MEK1 in colon associated with colon cancer and apoptosis

2) Confidence 0.61 Published 2004 Journal Cancer Res. Section Abstract Doc Link 15548677 Disease Relevance 1.23 Pain Relevance 0.14

Finally, blockade of ERK 1/2 phosphorylation with the mitogen-activated protein kinase (MEK) 1/2 inhibitor SL327 blocked alcohol-induced c-Fos expression, suggesting that alcohol induces c-Fos in Edinger-Westphal neurons through activation of the MEK1/2-ERK1/2-Stat3 pathway.

Positive_regulation (activation) of MEK1 in neurons associated with alcohol

3) Confidence 0.49 Published 2002 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 12130710 Disease Relevance 0 Pain Relevance 0.47

Sulindac sulfide treatment was associated with activation of ERKp44/42 and p38 MAPK in a dosage- and time-dependent manner, and also activated upstream MEK.

Positive_regulation (activated) of MEK

4) Confidence 0.14 Published 2005 Journal Mol. Cancer Ther. Section Abstract Doc Link 15657353 Disease Relevance 0.80 Pain Relevance 0.27

In conclusion, MEK/ERK and p38 MAPK activation mediate COX-2 induction by sulindac sulfide.

Positive_regulation (activation) of MEK

5) Confidence 0.14 Published 2005 Journal Mol. Cancer Ther. Section Abstract Doc Link 15657353 Disease Relevance 0.68 Pain Relevance 0.33

induces cell transformation in multiple cell types including human embryonic kidney and human mammary epithelial cells expressing hTERT, the SV40 Early Region, and constitutively active MEK (Fig. 6A), as well as in NIH 3T3 mouse fibroblasts (data not shown).

Positive_regulation (active) of MEK in epithelial cells

6) Confidence 0.06 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813871 Disease Relevance 0.36 Pain Relevance 0

PD98059 is a selective inhibitor of MEK1 activation and the ERK cascade, as it binds to the inactive forms of MEK1 and prevents activation by upstream activators.

Positive_regulation (activation) of MEK1

7) Confidence 0.04 Published 2010 Journal BMC Microbiol Section Body Doc Link PMC3022711 Disease Relevance 0.08 Pain Relevance 0

It directly phosphorylates and activates the SEK1 protein kinase, leading to activation of the stress activated protein kinase/jun N terminal kinase (SAPK/JNK) [1,2].

Positive_regulation (activates) of SEK1 protein kinase associated with stress

8) Confidence 0.03 Published 2007 Journal BMC Cancer Section Body Doc Link PMC2071920 Disease Relevance 0.51 Pain Relevance 0.08

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