INT196785

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.54
First Reported 2006
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 5
Total Number 14
Disease Relevance 2.10
Pain Relevance 1.17

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

cytosol (Ppp2ca) chromosome (Ppp2ca) plasma membrane (Ppp2ca)
cytoskeleton (Ppp2ca) nucleus (Ppp2ca) cytoplasm (Ppp2ca)
Anatomy Link Frequency
neuronal 1
2A1 1
Ppp2ca (Mus musculus)
Pain Link Frequency Relevance Heat
Dopamine 676 99.16 Very High Very High Very High
Glutamate 124 98.52 Very High Very High Very High
midbrain 44 87.40 High High
Calcium channel 8 75.84 Quite High
Neurotransmitter 22 74.00 Quite High
Catecholamine 60 65.04 Quite High
Potency 10 44.28 Quite Low
agonist 4 11.12 Low Low
Substantia nigra 94 5.00 Very Low Very Low Very Low
long-term potentiation 32 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Targeted Disruption 100 98.44 Very High Very High Very High
Parkinson's Disease 180 94.96 High High
Stress 20 92.20 High High
Disease 10 88.48 High High
Toxicity 20 69.08 Quite High
Neurodegenerative Disease 10 60.28 Quite High
Aging 30 57.72 Quite High
Apoptosis 30 13.20 Low Low
Pain 10 5.00 Very Low Very Low Very Low
Injury 10 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Taken together, the mouse data provide compelling support for a physiological contribution of a-Syn to the regulation of TH and PP2A in vivo.
Regulation (regulation) of PP2A
1) Confidence 0.54 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 Pain Relevance 0.03
Therefore, the third aim of this study was to assess if phosphorylation of a-Syn, in particular of Ser-129, affected PP2A or TH activity in vitro or in vivo.
Regulation (affected) of PP2A
2) Confidence 0.54 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.09 Pain Relevance 0
Although the exact mechanism underlying PP2A regulation by a-Syn is not yet defined, it likely involves a-Syn binding to the PP2A catalytic subunit based on our prior co-immunoprecipitation data (43) and our current findings using recombinant proteins, which require preincubation to affect PP2A activity (Fig. 7).
Regulation (regulation) of PP2A
3) Confidence 0.40 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.17
a-Syn Ser(P)-129 has been implicated in pathology (38, 95); however, whether Ser(P)-129 functionally affected PP2A activity or TH activity has never been evaluated.
Spec (whether) Regulation (affected) of PP2A
4) Confidence 0.40 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.60 Pain Relevance 0.17
To reproduce experimental data on DARPP-32 phosphorylation, the regulation of PP2A by both calcium and dopamine is required.
Regulation (regulation) of PP2A associated with dopamine
5) Confidence 0.39 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.20
Incorporating the effect of phosphoThr75 and the regulation of PP2A in our model made the stimulatory effect of calcium robust to parameter variations (Figure 8).
Regulation (regulation) of PP2A
6) Confidence 0.39 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.09
Dephosphorylation of DARPP-32 and regulation of PP2A.
Regulation (regulation) of PP2A
7) Confidence 0.39 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.10
Therefore, this study was undertaken to 1) further elucidate the molecular mechanisms underlying the effects of a-Syn on TH, especially Ser-19 phosphorylation, which represents a key step in 14-3-3-mediated-TH activation, 2) determine the in vivo significance of a-Syn in TH regulation in transgenic overexpressing and null mice, and 3) assess if a-Syn Ser-129 phosphorylation affects a-Syn function toward PP2A or TH.
Regulation (affects) of PP2A associated with targeted disruption
8) Confidence 0.24 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.56 Pain Relevance 0
Our studies using cell-free assays, dopaminergic neuronal cells, and four independent a-Syn mouse models have generated three major and novel findings regarding a-Syn-mediated regulation of TH and PP2A.
Regulation (regulation) of PP2A in neuronal
9) Confidence 0.24 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.06 Pain Relevance 0.03
Together these data imply that when a-Syn is dephosphorylated on Ser-129, the molecule becomes a more potent regulator of TH and PP2A than when Ser-129 on a-Syn is phosphorylated.
Regulation (regulator) of PP2A
10) Confidence 0.24 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.08
We found significant in vivo and in vitro effects of a-Syn on the regulation of TH and PP2A that are modulated by phosphorylation of a-Syn at Ser-129.
Regulation (regulation) of PP2A
11) Confidence 0.24 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.55 Pain Relevance 0
Delineating those mechanisms underlying a-Syn-mediated modulation of PP2A and TH holds promise to aid in the design of novel therapies to optimize dopaminergic neurotransmission for the treatment of PD, without overproducing potentially toxic dopamine levels.


Regulation (modulation) of PP2A associated with parkinson's disease and dopamine
12) Confidence 0.24 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.09 Pain Relevance 0.07
This regulation further appears to be selective, as another major PP2A target, the protein kinase B/Akt (58, 59), that does not bind a-Syn retains normal levels of phosphorylation in our a-Syn-overexpressing cells (44), suggesting the existence of a microdomain(s) where a-Syn localizes with PP2A and dopamine regulatory proteins (9, 31).


Spec (appears) Regulation (target) of PP2A associated with dopamine
13) Confidence 0.21 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.06 Pain Relevance 0.05
It is important to note that this modulation of PP2A by calcium has a minimal effect on the level of phosphoThr34 (Figure 2A1 and 2B1, dotted lines).
Regulation (modulation) of PP2A in 2A1
14) Confidence 0.17 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.18

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox