INT148540

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Context Info
Confidence 0.36
First Reported 2006
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 3
Total Number 19
Disease Relevance 1.28
Pain Relevance 4.89

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

phosphatase activity (Phospho1) cellular_component (Phospho1) biological_process (Phospho1)
Anatomy Link Frequency
DRG 1
2A1 1
microglia 1
Phospho1 (Mus musculus)
Pain Link Frequency Relevance Heat
Dopamine 2023 99.72 Very High Very High Very High
dorsal root ganglion 4 97.64 Very High Very High Very High
imagery 51 96.08 Very High Very High Very High
agonist 17 91.88 High High
Action potential 68 91.04 High High
Glutamate 527 87.52 High High
qutenza 1 86.32 High High
projection neuron 68 85.84 High High
Spinal cord 4 85.84 High High
long-term potentiation 136 80.72 Quite High
Disease Link Frequency Relevance Heat
Ganglion Cysts 4 97.64 Very High Very High Very High
Diabetes Mellitus 4 96.84 Very High Very High Very High
Hyperalgesia 3 95.84 Very High Very High Very High
Disease 1 75.68 Quite High
Demyelinating Disease 1 70.64 Quite High
Neuropathic Pain 1 69.72 Quite High
Peripheral Neuropathy 3 68.16 Quite High
Pain 1 5.00 Very Low Very Low Very Low
Nociception 1 5.00 Very Low Very Low Very Low
INFLAMMATION 1 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Functionally, these microglia respond to lipopolysaccharide incubation with increases in both phospho-p38 MAPK and OX42 immunostaining, as well as release of ATP, as compared to un-stimulated microglia.
Positive_regulation (increases) of phospho-p38 in microglia
1) Confidence 0.36 Published 2009 Journal J. Neurosci. Methods Section Abstract Doc Link 19596375 Disease Relevance 0.22 Pain Relevance 0.26
In summary, the PKA–PP2A–phosphoThr75 feedback loop is important for increasing levels of free PKAc and phosphoThr34, but only when transient calcium elevations are present, and not in response to transient inputs of dopamine alone.
Positive_regulation (increasing) of phosphoThr34 associated with dopamine
2) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.24
A persistent calcium elevation has a minimal effect on PKAc and decreases phosphoThr34, whereas a brief transient calcium elevation produces an increase in both PKAc and phosphoThr34.
Positive_regulation (increase) of phosphoThr34
3) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.84
This implies that if calcium-dependent activation of PP2A is eliminated, but the PKA–PP2A–phosphoThr75 loop is kept intact, pairing calcium and dopamine will give smaller elevations of free PKAc and phosphoThr34, than dopamine alone.
Positive_regulation (elevations) of phosphoThr34 associated with dopamine
4) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.17
If this pathway is omitted, a sustained stimulation of the D1 receptor instead leads to a small increase in phosphoThr75 (Figure 2A2, dashed line) in contrast to experimental data, though the increase in phosphoThr34 qualitatively remains unchanged.
Positive_regulation (increase) of phosphoThr34
5) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.28
More importantly, though calcium paired with dopamine produces a slight decrease in free PKAc, it produces an increase in phosphoThr34 (Figure 9B2).
Positive_regulation (increase) of phosphoThr34 associated with dopamine
6) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.25
Thus, without the calcium-dependent PP2A augmentation, a transient dopamine input alone is predicted to increase both PKAc activation and phosphoThr34 more effectively than dopamine paired with calcium.


Positive_regulation (increase) of phosphoThr34 associated with dopamine
7) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.31
Eight transient calcium pulses cause an increase in both PKAc and phosphoThr34 (Figure 6B, black lines) that is comparable to the increase caused with eight pulses of dopamine alone (compare Figure 6A).
Positive_regulation (increase) of phosphoThr34 associated with dopamine
8) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.14
Thus, when rates of reaction (i) and (iii) are set to zero (opening the loop), both PKAc and phosphoThr34 increase less compared with when the loop is fully active.
Positive_regulation (increase) of phosphoThr34
9) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.17
In contrast, the basal and stimulated levels of phosphoThr34 increase with a decrease in enzyme concentration (Figure 9A2, dotted lines).
Positive_regulation (increase) of phosphoThr34
10) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.15
The model is based on published biochemical data: the simulated regulation of DARPP-32 phosphorylation by sustained G-protein receptor activation and calcium influx fits experimental data, increasing and decreasing phosphoThr34, respectively (Figures 2 and 3).
Positive_regulation (increasing) of phosphoThr34
11) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.17
Nonetheless, the very high affinity of phosphoThr34 for PP1 implies that almost all phosphoThr34 is bound to PP1, and if Thr34 can be dephosphorylated only when unbound, phosphoThr34 increases to the amount of PP1.
Positive_regulation (increases) of phosphoThr34
12) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0
The increase in free PKAc due to paired stimuli is 40% greater than the increase observed with dopamine alone, whereas the peak increase in phosphoThr34 is more than doubled (Figure 5A and 5B, solid red lines).
Positive_regulation (increase) of phosphoThr34 associated with dopamine
13) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.34
The result that a transient calcium elevation can increase phosphoThr34 was shown with a previous model [69].
Positive_regulation (increase) of phosphoThr34
14) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.11
Surprisingly, opening the feedback loop increases the concentration of both PKAc (Figure 6A1, orange line) and phosphoThr34 (Figure 6A2, orange line) compared with the control condition (Figure 6A, black lines).
Positive_regulation (increases) of phosphoThr34
15) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.18
As demonstrated experimentally [23], the calcium increase inhibits the increase in phosphoThr34 caused by dopamine (Figure 3A, solid line), and enhances the decrease in phosphoThr75 (Figure 3B, solid line).
Positive_regulation (increase) of phosphoThr34 associated with dopamine
16) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.19
M increases the levels of phosphoThr34 9-fold within 2 min, comparable with the experimental observation of a 6–9-fold increase within 2 to 4 min [17] (Figure 2A1, solid line).
Positive_regulation (increases) of phosphoThr34 in 2A1
17) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.28
Western blot analysis revealed an increase in TRPV1 protein content and phospho p38 (p-p38) mitogen-activated protein kinase (MAPK) levels in DRG of STZ-injected diabetic and nondiabetic hyperalgesic mice compared with control mice.
Positive_regulation (increase) of phospho p38 in DRG associated with dorsal root ganglion, hyperalgesia and diabetes mellitus
18) Confidence 0.01 Published 2008 Journal Mol. Pharmacol. Section Abstract Doc Link 18089839 Disease Relevance 1.07 Pain Relevance 0.58
Calcium activation of the feedback loop is essential for the enhancement of PKAc and phosphoThr34 in response to paired stimuli.
Positive_regulation (enhancement) of phosphoThr34
19) Confidence 0.01 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.22

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