INT326427

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Context Info
Confidence 0.36
First Reported 2010
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 2
Total Number 18
Disease Relevance 1.32
Pain Relevance 0.83

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

RNA binding (Eif2ak2) nucleus (Eif2ak2) intracellular (Eif2ak2)
translation (Eif2ak2) kinase activity (Eif2ak2)
Anatomy Link Frequency
macrophages 2
B cells 1
fibroblasts 1
Eif2ak2 (Mus musculus)
Pain Link Frequency Relevance Heat
cytokine 87 95.56 Very High Very High Very High
Inflammation 138 95.16 Very High Very High Very High
tolerance 714 86.64 High High
addiction 17 75.88 Quite High
palliative 17 25.96 Quite Low
agonist 51 5.00 Very Low Very Low Very Low
Inflammatory mediators 17 5.00 Very Low Very Low Very Low
chemokine 17 5.00 Very Low Very Low Very Low
Central nervous system 1 5.00 Very Low Very Low Very Low
ketamine 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
INFLAMMATION 155 95.16 Very High Very High Very High
Attention Deficit Hyperactivity Disorder 17 94.80 High High
Stress 17 91.84 High High
Infection 171 89.20 High High
Targeted Disruption 51 88.16 High High
Parasitemia 13 74.16 Quite High
Thrombocytopenia 3 72.60 Quite High
Apoptosis 2 55.92 Quite High
African Trypanosomiasis 3 50.00 Quite Low
Hypergammaglobulinemia 4 42.92 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
V5-tagged wild-type (WT) PKR was overexpressed in HEK293T cells, along with expression vectors for WT hemagglutinin (HA)-tagged ubiquitin (HA-Ub) or HA-tagged ubiquitin bearing a single lysine at either position 48 or 63 (HA-K48 only or HA-K63 only).
Gene_expression (overexpressed) of PKR
1) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0.03
A high-molecular-weight, ubiquitinated PKR species was detected only when immunoprecipitated PKR was coexpressed with HA-tagged ubiquitin (Fig. 4A).
Gene_expression (coexpressed) of PKR
2) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0
For analysis of ubiquitination in HEK293T, 7.5 × 105 cells were plated in 6-well plates and transfected the following morning with constructs expressing tagged PKR and/or constructs expressing HA-tagged ubiquitin.
Gene_expression (expressing) of PKR
3) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0
To test this hypothesis, PKR was overexpressed in HEK293T cells, along with increasing concentrations of a SOCS-1 expression vector.
Gene_expression (overexpressed) of PKR
4) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.06 Pain Relevance 0.14
We observed a striking dose-dependent reduction in basal PKR protein expression levels in response to an increase in SOCS-1 following 24 h of incubation (Fig. 5B, top).
Gene_expression (expression) of PKR
5) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.06 Pain Relevance 0.12
Western analysis of whole-cell lysates revealed the expected reduction in PKR expression levels when coexpressed with SOCS-1 (Fig. 5D, bottom).
Gene_expression (expression) of PKR
6) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.07 Pain Relevance 0
V5-tagged WT PKR was transfected into HEK293T cells without or with concomitant transfection of FLAG-tagged SOCS-1, and immunoprecipitations were carried out with anti-FLAG monoclonal antibody.
Neg (without) Gene_expression (transfected) of PKR
7) Confidence 0.36 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0
Importantly, SOCS-2 overexpression had a negligible effect on the basal level of PKR, even at the highest dose (Fig. 5C).
Gene_expression (overexpression) of PKR
8) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0
PKR was immunoprecipitated only in the presence of cotransfected SOCS-1 (Fig. 5D, top).
Gene_expression (immunoprecipitated) of PKR
9) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.06 Pain Relevance 0
Why a loss of SOCS-1 results in dramatically and constitutively elevated levels of phosphorylated PKR, but not total PKR, is not entirely clear.
Gene_expression (levels) of PKR
10) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.15 Pain Relevance 0.04
LPS induced rapid K63 modification of PKR in naive RAW cells but not in LPS-tolerant cells.
Gene_expression (modification) of PKR
11) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0
Why a loss of SOCS-1 results in dramatically and constitutively elevated levels of phosphorylated PKR, but not total PKR, is not entirely clear.
Gene_expression (levels) of PKR
12) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.15 Pain Relevance 0.04
We also show that total PKR levels are elevated in LPS-tolerant murine macrophages but not in MEFs, a fact that may reflect the far greater LPS sensitivity of macrophages compared to that of embryonic fibroblasts.
Gene_expression (levels) of PKR in fibroblasts
13) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.09 Pain Relevance 0.16
The capacity of SOCS-1 to interact physically with and catalyze degradation of PKR in HEK293T cells supports the possibility that SOCS-1 regulates PKR protein levels during the TLR4-mediated response to LPS.
Gene_expression (levels) of PKR
14) Confidence 0.31 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0.09 Pain Relevance 0
Basal levels of polyubiquitinated PKR were barely detectable in naive RAW 264.7 macrophages, but rapid and robust high-molecular-weight, ubiquitinated PKR was detected 15 min after LPS stimulation and persisted until 90 min (Fig. 3B).
Gene_expression (detectable) of PKR in macrophages
15) Confidence 0.28 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0.10
For analysis of ubiquitination in HEK293T, 7.5 × 105 cells were plated in 6-well plates and transfected the following morning with constructs expressing tagged PKR and/or constructs expressing HA-tagged ubiquitin.
Gene_expression (expressing) of PKR
16) Confidence 0.28 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0
Basal levels of polyubiquitinated PKR were barely detectable in naive RAW 264.7 macrophages, but rapid and robust high-molecular-weight, ubiquitinated PKR was detected 15 min after LPS stimulation and persisted until 90 min (Fig. 3B).
Gene_expression (detected) of PKR in macrophages
17) Confidence 0.28 Published 2010 Journal mBio Section Body Doc Link PMC2962435 Disease Relevance 0 Pain Relevance 0.10
It is also possible that CpG-DNA motifs released from the parasite may trigger the production of IFN type I, lead to the intense activation of B cells and equally contribute to the expression of Sca-1 by bone marrow cells [32]–[34].
Gene_expression (production) of IFN type I in B cells
18) Confidence 0.04 Published 2010 Journal PLoS Neglected Tropical Diseases Section Body Doc Link PMC2919407 Disease Relevance 0.59 Pain Relevance 0.10

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