INT90273

Context Info Confidence 0.41 First Reported 2000 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 10 Total Number 15 Disease Relevance 0.82 Pain Relevance 2.71

mitochondrion (Ppp1cc) carbohydrate metabolic process (Ppp1cc) protein complex (Ppp1cc) cytoplasm (Ppp1cc) chromosome (Ppp1cc) nucleolus (Ppp1cc)

Anatomy Link Frequency myometrium 1 spine 1 Ppp1cc (Mus musculus)

Pain Link Frequency Relevance Heat Dopamine 604 99.24 long-term potentiation 119 98.92 gABA 99 96.80 interneuron 9 96.04 Glutamate 164 95.88 Calcium channel 11 94.88 depression 101 93.96 Nav1.6 14 90.08 Hippocampus 19 86.96 sodium channel 37 83.48

Disease Link Frequency Relevance Heat Adhesions 14 95.92 Depression 101 93.96 Targeted Disruption 104 78.24 Dysmenorrhea 4 74.56 Anxiety Disorder 32 50.00 Bardet-biedl Syndrome 1 20.72 Shock 7 5.00 Convulsion 4 5.00 Nociception 3 5.00 Pain 3 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

During the early prepubertal period PP1(alpha) was expressed in longitudinal myometrium and absent in circular myometrium; whereas, during the transition to sexual maturity PP1(alpha) was observed in both the longitudinal and circular myometrium.

Positive_regulation (observed) of PP1 in myometrium

1) Confidence 0.41 Published 2000 Journal Biol. Reprod. Section Abstract Doc Link 10952921 Disease Relevance 0.07 Pain Relevance 0.15

Considering the interaction of neurabin with PP1, it is reasonable to believe that neurabin is important in targeting PP1 to the dendritic spine, thereby modulating long-term plasticity.

Positive_regulation (targeting) of PP1 in spine

2) Confidence 0.33 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2169299 Disease Relevance 0.59 Pain Relevance 0.39

Since the phosphorylation state depends on the balance between kinases and phosphatases, the increase in PKAc to PP1 is likely to produce a significant change in several target molecules, as has been demonstrated for AMPA receptors [35].

Positive_regulation (increase) of PP1

3) Confidence 0.28 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.34

Calcium decreases PKA activity, and increases PP1 activity, whereas dopamine does the opposite.

Positive_regulation (increases) of PP1 associated with dopamine

4) Confidence 0.28 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.65

Calcineurin-mediated DARPP-32 dephosphorylation and PP-1 activation is a feedforward inhibitory pathway to CaMKII activation.

Positive_regulation (activation) of PP-1

5) Confidence 0.22 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0

In the RP suppression, strong CaMKII autophosphorylation at Thr286/287 caused by the large [Ca2+]i increase seems to be counteracted by potent activation of PP-1 synergistically brought about by the calcineurin activity triggered by the [Ca2+]i increase and the GABABR-mediated downregulation of adenylyl cyclase activity.

Positive_regulation (activation) of PP-1

6) Confidence 0.22 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.04

Thus, PP-1 activation caused by the PDE1 pathway peaks tens of seconds after the end of the [Ca2+]i increase, when the sustained CaMKII activation is established.

Positive_regulation (activation) of PP-1

7) Confidence 0.22 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0

More importantly, the increase in PKAc:PP1 in response to paired stimulation remains greater than the response to dopamine alone (Figure S2A), similar to simulations in which other enzymes were increased.

Positive_regulation (increase) of PP1 associated with dopamine

8) Confidence 0.20 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.25

Since the ratio PKAc:PP1 controls AMPA channel phosphorylation, this larger increase in PKAc:PP1 would translate into more LTP due to paired stimulation.

Positive_regulation (increase) of PP1 associated with long-term potentiation

9) Confidence 0.19 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.14

Since phosphorylation state depends on the balance between kinases and phosphatases, the increase in PKAc to PP1 is likely to produce a significant change in several target molecules, such as GABA [42] receptors, as well as sodium [43] and calcium channels [44], which will modify the subsequent response to synaptic stimulation.

Positive_regulation (increase) of PP1 associated with gaba and calcium channel

10) Confidence 0.19 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.23

Compared with the results without GABABR stimulation, the reductions of the cAMP and active PKA levels during the conditioning stimulation were larger (Figure 2G and H), and the duration of the increase in active PP-1 was longer (Figure 2J).

Positive_regulation (increase) of PP-1

11) Confidence 0.16 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0.04

Simultaneous activation of GABAB receptors suppresses the induction of rebound potentiation through the activation of protein phosphatase I (PP-1).

Positive_regulation (activation) of PP-1

12) Confidence 0.16 Published 2008 Journal Frontiers in Molecular Neuroscience Section Body Doc Link PMC2526003 Disease Relevance 0 Pain Relevance 0

As the amount of active CaMKII increased, active PP-1 decreased in a manner depending on PDE1 phosphorylation by CaMKII (Figure 5F).

Positive_regulation (increased) of PP-1

13) Confidence 0.15 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0 Pain Relevance 0

Recently, we reported that mGluR1 activity supports RP induction by facilitating the PKA/phospho-DARPP-32/PP-1 inhibition pathway (Sugiyama et al, 2008).

Positive_regulation (facilitating) of PP-1

14) Confidence 0.14 Published 2009 Journal Mol Syst Biol Section Body Doc Link PMC2710870 Disease Relevance 0.16 Pain Relevance 0.12

To increase RB INa amplitude, T4 may rapidly activate PP1 and/or inhibit p38.

Positive_regulation (activate) of PP1

15) Confidence 0.04 Published 2009 Journal Neural Dev Section Body Doc Link PMC2704202 Disease Relevance 0 Pain Relevance 0.37

General Comments

This test has worked.