INT150087

Context Info Confidence 0.44 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 5 Total Number 17 Disease Relevance 1.71 Pain Relevance 0.18

cytosol (PDCD10) Golgi apparatus (PDCD10) plasma membrane (PDCD10) cytoplasm (PDCD10)

Anatomy Link Frequency plasma 1 PDCD10 (Homo sapiens)

Pain Link Frequency Relevance Heat headache 17 95.88 withdrawal 13 54.84 Glutamate 26 22.76 Central nervous system 26 17.12 imagery 26 5.00

Disease Link Frequency Relevance Heat Headache Disorders 4 96.20 Epilepsy 4 95.44 Stroke 30 94.88 Apoptosis 117 81.44 Metastasis 13 76.28 Stress 13 72.32 Headache 13 34.20 Convulsion 13 33.36 Increased Venous Pressure Under Development 13 15.92 Aids-related Complex 13 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We therefore speculate that PDCD10-OSM and PDCD10-VEGFR2 interactions may be regulated by the availability of PtdIns(3,4,5)P3 generated by PI3K.

PDCD10 Binding (interactions) of

1) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

These observations, in combination with our previous data showing that PDCD10 selectively binds to phosphatidylinostiol bis- and trisphosphates, but binds PtdIns(3,4,5)P3 with strongest affinity, led us to hypothesize that this area could be a potential amphipathic helix that may play a role in PtdIns(3,4,5)P3 binding [28].

PDCD10 Binding (binds) of

2) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0.08 Pain Relevance 0

We also showed that PDCD10 binds to both phosphatidylinositol bis- or tris-phosphates, but seems to have the highest affinity to phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) [28].

PDCD10 Binding (binds) of

3) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0.46 Pain Relevance 0.03

It is possible that this colocalization is a result of PDCD10 and VEGFR2 interactions.

PDCD10 Binding (interactions) of

4) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

PtdIns(3,4,5)P3 goes on to bind PDCD10 and AKT.

PDCD10 Binding (bind) of

5) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

We therefore speculate that PDCD10-OSM and PDCD10-VEGFR2 interactions may be regulated by the availability of PtdIns(3,4,5)P3 generated by PI3K.

PDCD10-VEGFR2 Binding (interactions) of

6) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

These observations, in combination with our previous data showing that PDCD10 selectively binds to phosphatidylinostiol bis- and trisphosphates, but binds PtdIns(3,4,5)P3 with strongest affinity, led us to hypothesize that this area could be a potential amphipathic helix that may play a role in PtdIns(3,4,5)P3 binding [28].

PDCD10 Binding (binds) of

7) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0.08 Pain Relevance 0

The interaction of PDCD10 and PtdIns(3,4,5)P3 suggests that PDCD10 may function in concert with phosphatidylinositol-3-kinase (PI3K), the enzyme that catalyzes the formation of PtdIns(3,4,5)P3 at the plasma membrane [29].

PDCD10 Binding (interaction) of in plasma

8) Confidence 0.44 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0.18 Pain Relevance 0

Defining PtdIns(3,4,5)P3 binding site of PDCD10

PDCD10 Binding (site) of

9) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0.06 Pain Relevance 0

In the Membrane Lipid Array, WT PDCD10 binds weakly but specifically to phosphoserine (Fig. 4A).

PDCD10 Binding (binds) of

10) Confidence 0.33 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

However, it is not known which part of PDCD10 binds to PtdIns(3,4,5)P3 or OSM because there is currently no structural data available for PDCD10.

PDCD10 Binding (binds) of

11) Confidence 0.33 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0.31 Pain Relevance 0

These lysines are also important in PDCD10-OSM interaction.

PDCD10 Binding (interaction) of

12) Confidence 0.33 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

5KA of PDCD10 were bound to CNBr-activated sepharose beads (GE Biosciences) and incubated with 500 µg of cell lysate for 16 hours at 4°C.

PDCD10 Binding (bound) of

13) Confidence 0.30 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2909203 Disease Relevance 0 Pain Relevance 0

However, its ability to interact with CCM1 and to form a CCM1/CCM2/CCM3 complex was lost.

CCM3 Binding (interact) of

14) Confidence 0.25 Published 2008 Journal Hum. Mutat. Section Abstract Doc Link 18300272 Disease Relevance 0.10 Pain Relevance 0

Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex.

CCM3 Binding (complex) of

15) Confidence 0.19 Published 2008 Journal Hum. Mutat. Section Title Doc Link 18300272 Disease Relevance 0.29 Pain Relevance 0.10

The CCM2:p.P11_K68del protein could be expressed in cell culture and complexed with CCM3.

CCM3 Binding (complexed) of

16) Confidence 0.19 Published 2008 Journal Hum. Mutat. Section Abstract Doc Link 18300272 Disease Relevance 0.16 Pain Relevance 0.05

However, its ability to interact with CCM1 and to form a CCM1/CCM2/CCM3 complex was lost.

CCM3 Binding (complex) of

17) Confidence 0.19 Published 2008 Journal Hum. Mutat. Section Abstract Doc Link 18300272 Disease Relevance 0 Pain Relevance 0

General Comments

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