INT98647

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Context Info
Confidence 0.59
First Reported 2001
Last Reported 2010
Negated 0
Speculated 5
Reported most in Body
Documents 65
Total Number 70
Disease Relevance 32.93
Pain Relevance 15.67

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cell differentiation (Mdk) extracellular region (Mdk)
Anatomy Link Frequency
neurons 6
epithelial cells 4
liver 3
adipocytes 2
hepatocyte 1
Mdk (Mus musculus)
Pain Link Frequency Relevance Heat
Kinase C 108 100.00 Very High Very High Very High
addiction 72 100.00 Very High Very High Very High
unmyelinated 42 100.00 Very High Very High Very High
Delta opioid receptors 3 100.00 Very High Very High Very High
Cannabinoid receptor 2 100.00 Very High Very High Very High
Rostral ventrolateral medulla 165 99.68 Very High Very High Very High
qutenza 20 99.64 Very High Very High Very High
cytokine 527 99.60 Very High Very High Very High
Hyperalgesia 11 99.56 Very High Very High Very High
substance P 584 99.44 Very High Very High Very High
Disease Link Frequency Relevance Heat
Death 309 99.90 Very High Very High Very High
Hepatocellular Cancer 298 99.90 Very High Very High Very High
Obesity 1069 99.82 Very High Very High Very High
Colon Cancer 252 99.68 Very High Very High Very High
Metastasis 112 99.62 Very High Very High Very High
Hyperalgesia 77 99.56 Very High Very High Very High
Apoptosis 730 99.44 Very High Very High Very High
Malignant Neoplastic Disease 32 99.44 Very High Very High Very High
Nociception 74 99.34 Very High Very High Very High
Polycystic Kidney Disease 63 99.18 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We next investigated whether the reduced inflammatory nociception was associated with reduced ERK activation in the DN MEK mice.
Spec (whether) Positive_regulation (activation) of DN MEK associated with nociception and inflammation
1) Confidence 0.59 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.85 Pain Relevance 0.70
The increased number of unmyelinated fibers in the DN MEK mice could be a result of reduced ERK activity during development.
Positive_regulation (increased) of DN MEK associated with unmyelinated
2) Confidence 0.43 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.39 Pain Relevance 0.61
Although basal phosphorylated ERK is minimal in mouse spinal cords without noxious stimuli, we investigated whether expression of the DN MEK transgene would alter basal ERK activation in the DN MEK mice.
Spec (whether) Positive_regulation (activation) of DN MEK in spinal cords
3) Confidence 0.40 Published 2006 Journal Mol Pain Section Body Doc Link PMC1382249 Disease Relevance 0.50 Pain Relevance 0.40
As the downstream target of AC1, cyclic-AMP(cAMP)-dependent protein kinase (PKA) has been well documented, which may activate MEK and ERK/MAPK via the activation of AC1.
Positive_regulation (activate) of MEK
4) Confidence 0.38 Published 2007 Journal Mol Pain Section Body Doc Link PMC2245920 Disease Relevance 0 Pain Relevance 0.55
The effects of BDNF were mediated by receptor tyrosine kinase B (TrkB) and mitogen-activated protein kinase kinase (MEK) activation since culturing neurons with either (9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'- kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (K252a) or 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) blocked the augmentation in synaptic activity induced by the neurotrophin.
Positive_regulation (activation) of MEK in neurons
5) Confidence 0.32 Published 2007 Journal Neuroscience Section Abstract Doc Link 17306467 Disease Relevance 0 Pain Relevance 0.29
These effects are executed through a heterotrimeric G protein-coupled receptor, which mediates Ang II transactivated epidermal growth factor (EGF)-induced activation of MEK (MAPK kinase 1) and ERK [12].
Positive_regulation (activation) of MEK
6) Confidence 0.28 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2846883 Disease Relevance 0.59 Pain Relevance 0
Activation of the Raf/MEK/ERK cascade leads to changes in metabolism, transcription, and intracellular cytoskeletal arrangements (Marais et al 1997).
Positive_regulation (Activation) of MEK
7) Confidence 0.24 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661649 Disease Relevance 0.67 Pain Relevance 0
The presence of highly activated MEK1/2 in high grade HCCs suggests that MEK activation may tie into malignant progression of liver cancer.
Positive_regulation (activation) of MEK in liver associated with liver cancer and malignant neoplastic disease
8) Confidence 0.24 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 1.12 Pain Relevance 0
It was reasoned that MEK-MAPK activation in HCCs might enhance tumor cell proliferation and survival.
Positive_regulation (activation) of MEK associated with cancer
9) Confidence 0.24 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 0.76 Pain Relevance 0.03
To examine whether activated MEK was associated with the growth and survival of liver cancer cells, HepG2 cells were transfected with 5 ?
Spec (whether) Positive_regulation (activated) of MEK in liver associated with liver cancer
10) Confidence 0.24 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 0.15 Pain Relevance 0
Since constitutive MEK1 activation contributes to cell survival (Reviewed in [12]), we wished to determine if constitutive activation of MEK-MAPK in HepG2 cells would make the cells more resistant to U0126-induced apoptosis.
Positive_regulation (activation) of MEK associated with apoptosis
11) Confidence 0.24 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 0.40 Pain Relevance 0
In that regard, Kwak et al. [77] showed that AG-490, an inhibitor of Jak2/Jak3 activity, actually induced osteoclast survival by activating both the MEK/ERK and PI3K/PTEN/Akt cell survival pathway.
Positive_regulation (activating) of MEK in osteoclast
12) Confidence 0.22 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.47 Pain Relevance 0.38
Sorafenib inhibited activation of the Raf/MEK/ERK pathway in a number of cell lines in Western blot assays and pERK immunoassays (Wilhelm et al 2004).
Positive_regulation (activation) of MEK
13) Confidence 0.17 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661649 Disease Relevance 0.28 Pain Relevance 0
However, the role of MEK-MAPK activation in hepatogenesis and survival of hepatoma cells was not well understood.
Positive_regulation (activation) of MEK associated with hepatocellular cancer
14) Confidence 0.17 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 0.79 Pain Relevance 0.03
In parallel experiments, mice similarly treated with sorafenib were culled and Western blotting to investigate MEK and ERK activation was performed.
Spec (investigate) Positive_regulation (activation) of MEK
15) Confidence 0.16 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661649 Disease Relevance 0.61 Pain Relevance 0
Although activation of the MEK-MAPK is often associated with cellular growth, the role of MEK-MAPK in growth and survival of hepatocarcinoma cells has not been established.


Positive_regulation (activation) of MEK
16) Confidence 0.16 Published 2003 Journal BMC Gastroenterol Section Abstract Doc Link PMC317301 Disease Relevance 0.55 Pain Relevance 0
Treatment of human liver cancer cells with MEK1/2 inhibitor U0126 or PD98059, which inhibits MEK-MAPK activation, leads to a time- and dose-dependent reduction in cell proliferation and viability.
Positive_regulation (activation) of MEK in liver associated with liver cancer
17) Confidence 0.16 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 0.89 Pain Relevance 0.03
The immunohistochemistry and Western blot analysis of HCC samples suggested an important link between HCC and activation of the MEK-MAPK pathway.
Positive_regulation (activation) of MEK associated with hepatocellular cancer
18) Confidence 0.16 Published 2003 Journal BMC Gastroenterol Section Body Doc Link PMC317301 Disease Relevance 0.79 Pain Relevance 0.04
MEK is the key regulatory protein kinase activation in the Ras/Raf/MEK/ERK pathway (Figure 3).
Positive_regulation (activation) of MEK
19) Confidence 0.15 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.28 Pain Relevance 0.25
MEK is the key regulatory protein kinase activation in the Ras/Raf/MEK/ERK pathway (Figure 3).
Positive_regulation (activation) of MEK
20) Confidence 0.15 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.28 Pain Relevance 0.23

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