INT112905

Context Info Confidence 0.82 First Reported 2003 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 15 Total Number 16 Disease Relevance 2.78 Pain Relevance 2.30

embryo development (Cdk5) cytoplasm (Cdk5) cytosol (Cdk5) nucleocytoplasmic transport (Cdk5) cell death (Cdk5) nucleolus (Cdk5)

Anatomy Link Frequency growth cones 1 cingulate cortex 1 synapse 1 Cdk5 (Mus musculus)

Pain Link Frequency Relevance Heat Morphine 7 99.40 Calcium channel 13 99.30 ischemia 24 98.64 Neurotransmitter 18 97.76 Dopamine 521 97.60 Opioid 4 94.72 Neuronal excitability 18 94.08 adenocard 7 93.88 Glutamate 132 93.12 Neuropeptide 3 88.60

Disease Link Frequency Relevance Heat Transient Ischemic Attack 1 99.40 Shock 54 98.52 Injury 10 95.84 Convulsion 68 89.68 Cv Unclassified Under Development 14 84.64 Targeted Disruption 125 80.16 Disease 43 77.80 Drug Dependence 2 75.00 Alzheimer's Dementia 5 74.08 Death 31 72.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The level of phosphorylated-cdk5 was significantly increased in the cingulate cortex of mice showing the morphine-induced rewarding effect.

Phosphorylation (phosphorylated) of cdk5 in cingulate cortex associated with morphine

1) Confidence 0.82 Published 2005 Journal J. Neurochem. Section Abstract Doc Link 15935062 Disease Relevance 0.14 Pain Relevance 0.52

Cdk5 has specifically been implicated in exocytosis and endocytosis via phosphorylation of numerous substrates including synapsin, amphiphysin I, dynamin, and others [44]–[47].

Phosphorylation (phosphorylation) of Cdk5

2) Confidence 0.80 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2695674 Disease Relevance 0.63 Pain Relevance 0.24

It has been shown that (R)-roscovitine reduced hyperphosporylation of the Tau protein, a major CDK5 target, after transient cerebral ischemia in rat, mainly by inhibiting CDK5 [21].

Phosphorylation (hyperphosporylation) of CDK5 associated with transient ischemic attack and ischemia

3) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2920814 Disease Relevance 0.43 Pain Relevance 0.12

On the other hand, DARPP-32 becomes an inhibitor of PKA when it is phosphorylated on Thr75 by cyclin-dependent kinase 5 (Cdk5).

Phosphorylation (phosphorylated) of Cdk5

4) Confidence 0.55 Published 2010 Journal Frontiers in Neuroanatomy Section Body Doc Link PMC2955397 Disease Relevance 0.14 Pain Relevance 0.12

On the other hand, DARPP-32 becomes an inhibitor of PKA when it is phosphorylated on Thr75 by cyclin-dependent kinase 5 (Cdk5).

Phosphorylation (phosphorylated) of cyclin-dependent kinase 5

5) Confidence 0.55 Published 2010 Journal Frontiers in Neuroanatomy Section Body Doc Link PMC2955397 Disease Relevance 0.14 Pain Relevance 0.09

We have recently observed P2X3 receptor serine phosphorylation by Cdk5 to be a powerful negative regulator of receptor function [26].

Phosphorylation (phosphorylation) of Cdk5

6) Confidence 0.43 Published 2010 Journal Mol Pain Section Body Doc Link PMC2940876 Disease Relevance 0 Pain Relevance 0

Sema3A induced the phosphorylation and activation of Cdk5 by Fyn, which was essential for the collapse of sensory growth cones by Sema3A.

Phosphorylation (phosphorylation) of Cdk5 in growth cones associated with shock

7) Confidence 0.42 Published 2007 Journal BMC Dev Biol Section Body Doc Link PMC2217550 Disease Relevance 0.28 Pain Relevance 0.03

Fyn was also shown to phosphorylate Cdk5 and the PlexinA2 cytoplasmic domain [44].

Phosphorylation (phosphorylate) of Cdk5

8) Confidence 0.42 Published 2007 Journal BMC Dev Biol Section Body Doc Link PMC2217550 Disease Relevance 0.28 Pain Relevance 0.03

DARPP-32 is also phosphorylated by cyclin-dependent kinase 5 on Thr75, and the phosphorylated form of DARPP-32 at Thr75 inhibits protein kinase (PKA) activity.

Phosphorylation (phosphorylated) of cyclin-dependent kinase 5

9) Confidence 0.40 Published 2003 Journal Eur. J. Neurosci. Section Abstract Doc Link 12956723 Disease Relevance 0 Pain Relevance 0.21

Thr34 is phosphorylated by PKA and dephosphorylated by protein phosphatase 2B (PP2B or calcineurin) [16,21] whereas Thr75 is phosphorylated by the cyclin-dependent kinase 5 (cdk5) and dephosphorylated mainly by PP2A [15,17].

Phosphorylation (phosphorylated) of cdk5

10) Confidence 0.36 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.35

Thr34 is phosphorylated by PKA and dephosphorylated by protein phosphatase 2B (PP2B or calcineurin) [16,21] whereas Thr75 is phosphorylated by the cyclin-dependent kinase 5 (cdk5) and dephosphorylated mainly by PP2A [15,17].

Phosphorylation (phosphorylated) of cyclin-dependent kinase 5

11) Confidence 0.36 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.35

The catalytic subunit of PKA catalyses phosphorylation of DARPP-32 at Thr34 [73,107]; Cdk5 catalyses phosphorylation of DARPP-32 at Thr75 [15].

Phosphorylation (phosphorylation) of Cdk5

12) Confidence 0.35 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0.03

Little is known about the regulation of Cdk5, but experiments show that there is a basal level of phosphorylation at Thr75 due to Cdk5 activity [108].

Phosphorylation (phosphorylation) of Cdk5

13) Confidence 0.35 Published 2006 Journal PLoS Computational Biology Section Body Doc Link PMC1562452 Disease Relevance 0 Pain Relevance 0

This increases the stability of the p25-CDK5 complex, alters its subcellular localization, and eventually results in the hyperphosphorylation of tau [97].

Phosphorylation (hyperphosphorylation) of CDK5

14) Confidence 0.25 Published 2009 Journal Microb Cell Fact Section Body Doc Link PMC2674406 Disease Relevance 0.61 Pain Relevance 0

Because CASK is involved in synaptic targeting of N-type calcium channels (Maximov and Bezprozvanny, 2002), phosphorylation of CASK by CDK5 modulates presynaptic calcium influx and controls synapse formation (Samuels et al., 2007).

Phosphorylation (phosphorylation) of CDK5 in synapse associated with calcium channel

15) Confidence 0.23 Published 2008 Journal The Journal of Cell Biology Section Body Doc Link PMC2447900 Disease Relevance 0.08 Pain Relevance 0.12

In addition to spinogenesis, CASK also acts presynaptically to regulate synaptogenesis through a different mechanism: CDK5 phosphorylates residues S51 and S395 of CASK proteins, which enhances the interaction between CASK and N-type calcium channels but impairs the interaction between CASK and liprin-?

Phosphorylation (phosphorylates) of CDK5 associated with calcium channel

16) Confidence 0.23 Published 2008 Journal The Journal of Cell Biology Section Body Doc Link PMC2447900 Disease Relevance 0.05 Pain Relevance 0.09

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