INT110178

Context Info Confidence 0.68 First Reported 2003 Last Reported 2011 Negated 1 Speculated 0 Reported most in Body Documents 40 Total Number 45 Disease Relevance 19.38 Pain Relevance 10.37

cytosol (MAPK14) nucleoplasm (MAPK14) signal transduction (MAPK14) nucleus (MAPK14) response to stress (MAPK14) cytoplasm (MAPK14)

Anatomy Link Frequency chondrocytes 2 MDMs 1 nervous system 1 microglia 1 spinal 1 MAPK14 (Homo sapiens)

Pain Link Frequency Relevance Heat cytokine 422 99.76 Inflammation 617 99.50 aspirin 11 99.46 dexamethasone 119 99.44 Rheumatism 2 99.12 cINOD 22 98.98 Nicotine 192 98.96 Neuropathic pain 8 98.92 Osteoarthritis 906 98.88 Arthritis 61 98.68

Disease Link Frequency Relevance Heat Apoptosis 274 99.80 Obesity 384 99.76 Targeted Disruption 47 99.74 INFLAMMATION 648 99.50 Injury 32 99.38 Cancer 254 99.24 Rheumatic Diseases 8 99.12 Neuropathic Pain 14 98.92 Osteoarthritis 920 98.88 Arthritis 71 98.68

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Next, we investigated the effect of MKK3 or MKK6 knock down on the phosphorylation of p38-MAPK in response to stimulation with IL-1?

Phosphorylation (phosphorylation) of p38 associated with targeted disruption

1) Confidence 0.68 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.09 Pain Relevance 0.45

-induced phosphorylation of p38-MAPK was inhibited in chondrocytes pre-treated with PE (Figure 4a).

Phosphorylation (phosphorylation) of p38 in chondrocytes

2) Confidence 0.68 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.73 Pain Relevance 0.36

(10 ng/ml) for different time periods (5 to 120 minutes) phosphorylated the p38-MAPK protein (Figure 2a).

Phosphorylation (phosphorylated) of p38

3) Confidence 0.60 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 1.09 Pain Relevance 0.45

Human phosphorylated p38 MAP Kinase protein was detected with anti-phospho-p38 MAP Kinase antibody (Thr180/Tyr182) (Cell Signaling, Ozyme, Saint Quentin Yvelines, France) antibody at a 1/1000 dilution.

Phosphorylation (phosphorylated) of p38 MAP Kinase

4) Confidence 0.54 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2819999 Disease Relevance 0 Pain Relevance 0

MKK3 selectively phosphorylates p38?

Phosphorylation (phosphorylates) of p38

5) Confidence 0.52 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.46 Pain Relevance 0.26

enhances the phosphorylation of the p38?

Phosphorylation (phosphorylation) of p38

6) Confidence 0.52 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2991031 Disease Relevance 0.80 Pain Relevance 0.40

alone had higher level of p38-MAPK phosphorylation compared with unstimulated OA chondrocytes.

Phosphorylation (phosphorylation) of p38 in chondrocytes associated with osteoarthritis

7) Confidence 0.52 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2991031 Disease Relevance 0.74 Pain Relevance 0.37

The phosphorylation of p38 MAPK and c-Jun NH2-terminal kinase (JNK) were detected after capsaicin stimulation. p38 MAPK is involved in capsaicin-induced IL-6 production, as shown by the use of specific inhibitors of this kinase.

Phosphorylation (phosphorylation) of p38 associated with qutenza

8) Confidence 0.46 Published 2005 Journal J Endod Section Abstract Doc Link 16123700 Disease Relevance 0.16 Pain Relevance 0.88

Suppression of AP-1 was associated with altered phosphorylation of p38 mitogen-activated protein kinases.

Phosphorylation (phosphorylation) of p38

9) Confidence 0.42 Published 2004 Journal Anesthesiology Section Body Doc Link 15329596 Disease Relevance 0 Pain Relevance 0

M) greatly decreases the LPS induced phosphorylation of the p38 protein, resulting in a level that is near identical to the control.

Phosphorylation (phosphorylation) of p38

10) Confidence 0.41 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2819999 Disease Relevance 0.09 Pain Relevance 0

Figure 2 confirms that the action of LPS on mature adipocytes results in p38 protein phosphorylation with a peak obtained 5 minutes after stimulation.

Phosphorylation (phosphorylation) of p38 in adipocytes associated with obesity

11) Confidence 0.41 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2819999 Disease Relevance 0.10 Pain Relevance 0

The quantity of phosphorylated p38 protein subsequently decreases and is no longer detectible 20 minutes after treatment with LPS.

Phosphorylation (phosphorylated) of p38

12) Confidence 0.41 Published 2010 Journal J Inflamm (Lond) Section Body Doc Link PMC2819999 Disease Relevance 0.10 Pain Relevance 0

AEA triggered phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen activated protein kinase.

Phosphorylation (phosphorylation) of p38

13) Confidence 0.41 Published 2003 Journal Thromb. Haemost. Section Abstract Doc Link 12719786 Disease Relevance 0.82 Pain Relevance 0.20

ET-1 at 10 nM induced p38, Akt, p44/42, and SAP/JNK phosphorylation in a time-ordered manner.

Phosphorylation (phosphorylation) of p38

14) Confidence 0.41 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.05 Pain Relevance 0

As shown by western blot analysis of the cell extracts, incubation of cells for a short period of time with ET-1 results in the phosphorylation of p38 MAP, p44/42, SAP/JNK and Akt kinases.

Phosphorylation (phosphorylation) of p38 MAP

15) Confidence 0.41 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.09 Pain Relevance 0.04

Figure 3a–d show the effects of ET-1 on the phosphorylation of p38, Akt, p44/42 and SAP/JNK kinases as detected by western blot of cell extracts.

Phosphorylation (phosphorylation) of p38

16) Confidence 0.41 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0 Pain Relevance 0

Both aspirin-mediated permeability and phosphorylation of p38 MAPK were significantly attenuated by SB-203580 (a p38 MAPK inhibitor) but not by U-0126 (a MEK1 inhibitor) or SP-600125 (a JNK inhibitor).

Phosphorylation (phosphorylation) of p38 associated with aspirin

17) Confidence 0.35 Published 2008 Journal Am. J. Physiol., Cell Physiol. Section Abstract Doc Link 18667601 Disease Relevance 0.14 Pain Relevance 0.39

Thrombin induced phosphorylation of ERK1/2 and p38 in MDMs.

Phosphorylation (phosphorylation) of p38 in MDMs

18) Confidence 0.34 Published 2009 Journal Blood Section Abstract Doc Link 19652200 Disease Relevance 0.98 Pain Relevance 0.30

The membranes were immersed overnight in the Super Block Blocking buffer (Pierce, Rockford, IL, USA), rinsed and incubated for 24 hours at 4°C with one of the mouse monoclonal primary antibodies (New England Biolabs, Mississauga, ON, Canada) specifically recognizing phosphorylated p38 or total p38 (dilution, 1/1000), phosphorylated p44/42 (dilution, 1/5000), phosphorylated Akt (dilution, 1/2000), phosphorylated stress-activated protein kinase/Jun-N-terminal kinase (SAP/JNK) (dilution, 1/1000), or actin C-terminal fragment (dilution, 1/5000). iNOS was detected with a rabbit polyclonal antibody (dilution, 1/1000; Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA).

Phosphorylation (phosphorylated) of p38 associated with stress

19) Confidence 0.31 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1065327 Disease Relevance 0.16 Pain Relevance 0.03

Additionally, inducible nitric oxide synthase (iNOS) and phosphorylated forms of p38 mitogen-activated protein kinase, p44/42, stress-activated protein kinase/Jun-N-terminal kinase and serine-threonine Akt kinase were determined by western blot.

Phosphorylation (phosphorylated) of p38 associated with stress

20) Confidence 0.31 Published 2005 Journal Arthritis Res Ther Section Abstract Doc Link PMC1065327 Disease Relevance 0.26 Pain Relevance 0.04

General Comments

This test has worked.