INT264972

Context Info Confidence 0.65 First Reported 2009 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 4 Total Number 14 Disease Relevance 6.92 Pain Relevance 3.68

cytosol (MAP2K3) nucleoplasm (MAP2K3) signal transduction (MAP2K3)

Anatomy Link Frequency chondrocytes 7 A549 1 MAP2K3 (Homo sapiens)

Pain Link Frequency Relevance Heat Osteoarthritis 1133 99.60 Arthritis 89 83.92 Opioid 67 75.60 analgesia 20 75.28 metalloproteinase 66 65.36 IPN 19 65.36 Inflammation 214 64.12 cytokine 92 60.80 agonist 17 54.88 rheumatoid arthritis 44 54.56

Disease Link Frequency Relevance Heat Osteoarthritis 1144 99.60 Carcinoma 2 94.24 Arthritis 102 83.92 Disease 85 79.36 Inflammatory Pain 19 65.36 Stress 11 64.76 INFLAMMATION 192 64.12 Rheumatoid Arthritis 44 54.56 Targeted Disruption 42 53.44 Nociception 24 50.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

-induced phosphorylation/activation of both MKK3 and MKK6, but the effect was more pronounced on MKK3 in primary human OA chondrocytes.

Positive_regulation (phosphorylation/activation) of MKK3 in chondrocytes associated with osteoarthritis

1) Confidence 0.65 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.54 Pain Relevance 0.24

-induced activation of MKK3 and MKK6 in human OA chondrocytes, cells were pretreated with PE (6.25 to 100 ?

Positive_regulation (activation) of MKK3 in chondrocytes associated with osteoarthritis

2) Confidence 0.65 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.71 Pain Relevance 0.33

-induced activation of MKK3 and MKK6 in human OA chondrocytes

Positive_regulation (activation) of MKK3 in chondrocytes associated with osteoarthritis

3) Confidence 0.65 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.60 Pain Relevance 0.30

-induced activation of MKK3 and MKK6 in primary human OA chondrocytes.

Positive_regulation (activation) of MKK3 in chondrocytes associated with osteoarthritis

4) Confidence 0.65 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.49 Pain Relevance 0.24

Thus, treatment with PE affects particularly the activation of MKK3 which in turn has an impact on the activation of p38-MAPK downstream (summarized in Figure 6).

Positive_regulation (activation) of MKK3

5) Confidence 0.47 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.68 Pain Relevance 0.25

Expression and activation of MKK3 and MKK6 in human OA chondrocytes

Positive_regulation (activation) of MKK3 in chondrocytes associated with osteoarthritis

6) Confidence 0.43 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.43 Pain Relevance 0.22

Thus, our results suggest that PE or PE-derived compounds may be useful in blocking the activation of MKK3 and might provide the benefit of p38-MAPK inhibition and its downstream targets such as RUNX-2 without the direct inhibition of p38-MAPK in OA.

Positive_regulation (activation) of MKK3 associated with osteoarthritis

7) Confidence 0.43 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.78 Pain Relevance 0.41

-induced activation of MKK3/6, p38-MAPK isoforms and the activation of transcription factor RUNX-2 in primary human OA chondrocytes.

Positive_regulation (activation) of MKK3 in chondrocytes associated with osteoarthritis

8) Confidence 0.43 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2991031 Disease Relevance 0.53 Pain Relevance 0.27

preferentially activates MKK3 in human OA chondrocytes.

Positive_regulation (activates) of MKK3 in chondrocytes associated with osteoarthritis

9) Confidence 0.43 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.59 Pain Relevance 0.29

preferentially activates MKK3 ?

Positive_regulation (activates) of MKK3

10) Confidence 0.43 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.62 Pain Relevance 0.31

-induced activation of MKK3, p38?

Positive_regulation (activation) of MKK3

11) Confidence 0.43 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2991031 Disease Relevance 0.68 Pain Relevance 0.34

The activation of MAP3K1 and MAP2K3 by r-ceramide exposure of A549 cells suggested that this pathway might be involved upstream of IRF3.

Positive_regulation (activation) of MAP2K3 in A549

12) Confidence 0.24 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2944801 Disease Relevance 0 Pain Relevance 0

Ceramide activated IL-6 transcription (6.2-fold), MAP3K1 and MAP2K3 (5.9- and 2.5-fold), as well as IL-8 and CSF2 transcription levels (about 3-fold).

Positive_regulation (activated) of MAP2K3

13) Confidence 0.16 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2944801 Disease Relevance 0.09 Pain Relevance 0

FPRs are coupled to Gi proteins [24] and receptor activation triggers intracellular signaling through phospholipase C, diacylglycerol, inositol phosphates and Ca2+ mobilization from intracellular stores, as well as activation of phosphoinositol-3 kinase (PI3K) [32].

Positive_regulation (activation) of phosphoinositol-3 kinase

14) Confidence 0.01 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2657213 Disease Relevance 0.18 Pain Relevance 0.49

General Comments

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