INT142992

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Context Info
Confidence 0.80
First Reported 2007
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 3
Total Number 24
Disease Relevance 0.87
Pain Relevance 1.28

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

cell differentiation (RHOA) mitochondrion (RHOA) cell morphogenesis (RHOA)
intracellular (RHOA) GTPase activity (RHOA) cytoplasm (RHOA)
Anatomy Link Frequency
neuronal 1
smooth muscle 1
intermediary 1
band 1
RHOA (Homo sapiens)
Pain Link Frequency Relevance Heat
Morphine 4 99.30 Very High Very High Very High
agonist 289 99.28 Very High Very High Very High
Serotonin 3 97.90 Very High Very High Very High
narcan 3 70.80 Quite High
antagonist 24 66.44 Quite High
mu opioid receptor 1 56.68 Quite High
Angina 23 53.60 Quite High
Inflammation 1 46.36 Quite Low
imagery 44 19.60 Low Low
Disease Link Frequency Relevance Heat
Injury 2 91.36 High High
Increased Venous Pressure Under Development 26 90.32 High High
Leukemia 22 85.68 High High
Coronary Vasospasm 3 77.56 Quite High
Thrombosis 66 63.04 Quite High
Adult Respiratory Distress Syndrome 1 49.68 Quite Low
Sepsis 1 48.80 Quite Low
Cancer 1 46.92 Quite Low
INFLAMMATION 1 46.36 Quite Low
Edema 2 45.20 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Morphine, DAMGO, thrombin, and LPS induced RhoA/ROCK-mediated threonine phosphorylation of S1P(3), which was blocked by MNTX, suggesting S1P(3) transactivation.
Phosphorylation (phosphorylation) of RhoA associated with morphine
1) Confidence 0.80 Published 2007 Journal Am. J. Respir. Cell Mol. Biol. Section Abstract Doc Link 17395891 Disease Relevance 0 Pain Relevance 0.59
Whilst it has not as yet been established whether the “molecular switch mechanism” resulting from RhoAS188 phosphorylation proposed by Nusser et al. [47] to exist in neuronal cells can be extended to other cell/tissue types, such as smooth muscle, it is tempting to speculate.
Phosphorylation (phosphorylation) of RhoA in smooth muscle
2) Confidence 0.80 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
Clearly many of the actions of cAMP and cGMP on RhoA signaling are mediated through their respective second messenger kinases PKA and PKG, respectively [6,35,36,43] and more recently it has been established that this may largely occur through their direct phosphorylation of RhoA itself at an identical site, namely Ser188 within its hypervariable region [36,42,44,45].
Phosphorylation (phosphorylation) of RhoA
3) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
in addition to the more general type of regulation through Ser188 phosphorylation of RhoA.
Phosphorylation (phosphorylation) of RhoA
4) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
is not a direct target for either PKA or PKG phosphorylation or inhibition, but its RhoA-mediated signaling would be sensitive to RhoA phosphorylation by either second messenger kinase.
Phosphorylation (phosphorylation) of RhoA
5) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
From their studies, they proposed that Ser188 phosphorylation of RhoA may act as a ‘secondary molecular switch’ capable of overriding GTP-elicited activation of certain RhoA effectors, such as ROCK, but directing it to signal with (an)other subset of Rho effectors, perhaps in a cell specific manner.
Phosphorylation (phosphorylation) of RhoA
6) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
Whilst phosphorylation of RhoA at Ser188 does not apparently alter its association with either RhoGEFs or RhoGAPs (GTPase activating proteins), it significantly increases its interaction with RhoGDI (GDP dissociation inhibitor) thereby reducing the level of membrane bound RhoA and impairing its ability to activate its key effectors including Rho Kinases [36,46].
Phosphorylation (phosphorylation) of RhoA
7) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
both SIN-1 and Cicaprost reduced U46619-mediated RhoA, F-actin polymerization (data not shown) and cofilin phosphorylation to levels not significantly different to those observed in vehicle-treated cells.
Phosphorylation (phosphorylation) of RhoA
8) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
is not subject to direct PKA or PKG phosphorylation, its signaling by prostacyclin or NO may only be regulated at downstream intermediary level(s), such as at the level of RhoA phosphorylation.
Phosphorylation (phosphorylation) of RhoA in intermediary
9) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
All images of RhoA expression/pulldown or cofilin phosphorylation and/or expression were captured using Adobe Photoshop (V6), where band width and intensity was quantified and represented as fold increases relative to basal levels.
Phosphorylation (phosphorylation) of RhoA in band
10) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
-mediated RhoA signalling, both NO and prostacyclin directly target RhoA phosphorylation at Ser188 through their regulation of PKG and PKA signaling, respectively (data not shown).
Phosphorylation (phosphorylation) of RhoA
11) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
As expected, stimulation of cultured 1° h.AoSMCs with U46619 led to a concentration-dependent RhoA activation, F-actin polymerization and cofilin phosphorylation.
Phosphorylation (phosphorylation) of RhoA
12) Confidence 0.58 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0.13
Consistent with this, the specific PGD2 receptor (DP) agonist BW245C also significantly impaired RhoA activation (Fig. 7C) and cofilin phosphorylation in 1° h.AoSMCs.
Phosphorylation (phosphorylation) of RhoA associated with agonist
13) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0.09
qQ209l,D277N), significantly impaired U46619-mediated RhoA activation and cofilin phosphorylation.
Phosphorylation (phosphorylation) of RhoA
14) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0.09 Pain Relevance 0.04
-mediated [Ca2+]i mobilization and the G12/RhoGEF-dependent RhoA activation and cofilin phosphorylation by TP?
Phosphorylation (phosphorylation) of RhoA
15) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0.12
Similarly, while the NO donors SIN-1 and FK409 alone did not induce substantial RhoA signaling relative to the drug vehicle per se, they each significantly impaired U46619-induced RhoA activation and cofilin phosphorylation following their pre-incubation in 1° h.AoSMCs (Fig. 7B and D).
Phosphorylation (phosphorylation) of RhoA
16) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0.08
From their studies, they proposed that Ser188 phosphorylation of RhoA may act as a ‘secondary molecular switch’ capable of overriding GTP-elicited activation of certain RhoA effectors, such as ROCK, but directing it to signal with (an)other subset of Rho effectors, perhaps in a cell specific manner.
Phosphorylation (phosphorylation) of RhoA
17) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
Consistent with the latter data, the PGD2 analogue BW245C and the alternative NO donor FK409 also significantly impaired U46619-mediated RhoA activation (Fig. 3C) and cofilin phosphorylation (data not shown) by TP?
Phosphorylation (phosphorylation) of RhoA
18) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
Moreover, in a recent study investigating NGF-mediated RhoA responses in neuronal PC12 cells, Nusser et al. provided in vitro and in vivo evidence to suggest that Ser188 phosphorylation of RhoA impairs activation of Rho kinase (ROCK 1/2), but does not affect its ability to activate other Rho effectors including rhotekin, mDia-1 and PKN [47].
Phosphorylation (phosphorylation) of RhoA in neuronal
19) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0
While SIN-1 and Cicaprost significantly impaired U46619-mediated RhoA activation in the presence of the siRNA directed to Lamin A/C to levels similar to that in vehicle-treated cells, the inhibitory action of both agents on RhoA activation and cofilin phosphorylation in 1° h.AoSMCs exposed to the siRNATP?
Phosphorylation (phosphorylation) of RhoA
20) Confidence 0.45 Published 2008 Journal Cellular Signalling Section Body Doc Link PMC2681257 Disease Relevance 0 Pain Relevance 0

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