User:Etienne Robillard/Notebook/EGFR

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== Useful links on EGF(R)-mediated drug delivery ==
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== EGF(R)-mediated drug delivery ==
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* http://nrresource.org/Pathways/VDR%20Targets/92391.html
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* First please see this paper for background info on EGF(R) targeting [http://nrresource.org/Pathways/VDR%20Targets/92391.html here].
 +
* Second, the aim of this wiki is to review the characterization of cancerogenic mutations occuring in multiple receptor-associated tyrosine kinase proteins targeting the EGF receptor and perhaps in cholesterol based lipid rafts including stearic acid (monosaturated) and fatty acids derived ligands expressing the '''Fyn''' gene.
 +
* Further, the relationship between [http://openwetware.org/wiki/JHIBRG:Abstract_Apr_19_2007 MAP kinase signaling cascades] and EGFR-mediated over-expression is not fully understood.
 +
* Thus it is not fully understood how small molecules aggregation (beta-amyloid) can modulate NMDA mediated neuronal distribution in the Hippocampus.
 +
 +
__TOC__
 +
 
 +
 
 +
=== Glossary ===
 +
* cytotoxic: toxicity factor to cells
 +
* cytoplasm: outer edge of the cell membrane
 +
* oxidative phosphorylation: a enzymatic reaction converting energy from phosphate cleaving molecules to ATPase and NADPH substrates.
 +
* Fyn: A cell-dependent tyrosine kinase ligand associated to the Fyn oncogene
 +
* Src: tyrosine kinase bound protein (GRB2/Ash) encoded by the c-Src gene divided in 3 receptor-associated domains (SH2, SH3, and PH).
 +
* Tyrosine kinase: Tyrosine specific kinase (enzyme) member of the protein-coding kinases super family.
=== Case studies ===
=== Case studies ===
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* Breast cancer epithelial stem cells switching and the risks of EGF(R)-targeted phosphorylation:
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==== Breast cancer epithelial stem cells switching and the risks of EGF(R)-targeted (Fyn/Src) phosphorylation ====
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** [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408375/ Epithelial Stem Cells: Turning over New Leaves] (Rockefeller University)
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* '''Receptor-associated''' tyrosine kinase signaling (SH1/SH2 ?) for targeted drug delivery to epithelial stem cells membranes?
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Selected readings:
 +
* [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408375/ Epithelial Stem Cells: Turning over New Leaves] (Rockefeller University)
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* [http://www.uniprot.org/uniprot/P06241 Fyn (EC 2.7.10.2)]
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* Signal Transduction Cascades: http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/signals.htm#camp
 +
* cAMP-dependent protein kinase type I-beta regulatory subunit: http://www.uniprot.org/uniprot/P31321
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* cAMP-dependent protein kinase catalytic subunit alpha: http://www.uniprot.org/uniprot/P17612
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* cAMP-dependent protein kinase type I-alpha regulatory subunit: http://www.uniprot.org/uniprot/P10644
 +
** OMIM.org Entry : http://www.omim.org/entry/188830 Gene found to be relevant for many site-directed cross-talk (mutagenesis) in the presence of elevated cAMP levels.
 +
* Amyloid beta A4 protein: http://www.uniprot.org/uniprot/P05067
 +
 
 +
==== Chemopreventive role of bioflavonoids and endocannabinoids in mitigating long-term oxidative species from EGFR targeted pathway? Study Curcuma Longa... ====
 +
 
 +
Questions:
 +
* Is aerosol-based geoengineering hidden a systemic population control agenda using clouds as the medium and proteases as the cell-based factory for cancerogenic mutations?
 +
** If so, how can EGFR-based targeting compares to protein phosphatase inhibitor drugs (ie Imidazole) by "selectively" blocking tyrosine kinases phosphorylation ?
 +
* What other ligases (ATPase/cAMP?) can be metabolized from long-term exposure to a DNA alkylating agent ?
 +
* Is therefore the chemtrails system hiding in plain sight a pernicious eugenic model for long-term human based experiments on unwary civilians as during the Shoah? (chemotherapy.owl) 
 +
* See also [http://chemwiki.ucdavis.edu/Organic_Chemistry/Virtual_Textbook_of_OChem/Amines/Nomenclature_and_Structure_of_Amines/Natural_Nitrogen_Compounds Natural Nitrogen Compounds]
 +
 
 +
Notes:
 +
* '''Receptor-associated''' tyrosine kinase signaling (SH2/SH3) for targeted drug delivery to epithelial stem cells membranes?
 +
** Calmodulin-dependent protein kinase receptors (Ca2+) signal transduction linked to Alzheimer like neuronal dysregulation? (ie: PH based phospholipid dysregulation) ?
 +
** [http://www.alzforum.org/new/detail.asp?id=1446 Endocannabinoids: Wet Blanket on Hippocampus Excitement]: What does this signify for lipid-rafts based EGFR ligands ?
 +
*** '''Hippocampus''' dysregulation from calcium-dependent '''lipid-like''' signaling networks?
 +
**** [[User:Etienne Robillard|Etienne Robillard]] 08:56, 4 May 2012 (EDT): 420 like (CB1 '''receptors''') to the rescue..? :)
 +
**** In other words, how can '''anandamide''' (endocannabinoids) be used as novel therapeutic to mediates neuronal dysregulation of the hippocampus and in particular breast cancer early cancerogenic mutations ?
 +
***** Question: Is AChr dependent protein binding from endocannabinoid-specific activation (CB1-associated?):
 +
***** Endocannabinoid-specific receptors preventing beta amyloid precursors (β-amyloid peptide (Aβ)) aggregating in lipid rafts from cell-protein (AChr) promoted binding site(s), thus autocleaving phospholipid residues from oxidative radicals ? (gp42 link?)
 +
***** Question: How can tyrosine kinase derived substrates (from enzymatic reactions in C-domain (SH2) and N-domain (SH3)) can have a orthogonal role in Alzheimer pathogenesis '''and''' in targeted drug delivery?
 +
***** Answer: As emerging hypothesis, phosphorylation-induced tyrosine kinase drug delivery and upregulation to epithelial stem cells may probably result in asymmetrical protein binding in cholesterol-based microdomains (lipid rafts) with '''ErbB''' specific ligands, thus triggering a signal transduction cascade from the activated Src/Fyn receptors.
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=== TODO ===
+
== TODO ==
* Is programmed cell-death from '''cell-specific''' DNA based gene regulation via p53 gene/protein is leading to cell apoptosis? If so, could DNA programmed apoptosis result from aggregated nanoparticles to epithelial/endothelial stem cells membranes (ie: immunoglobin-like domain receptor) ?
* Is programmed cell-death from '''cell-specific''' DNA based gene regulation via p53 gene/protein is leading to cell apoptosis? If so, could DNA programmed apoptosis result from aggregated nanoparticles to epithelial/endothelial stem cells membranes (ie: immunoglobin-like domain receptor) ?
* Glycoproteins role in programmed cell division acting as a master toll-like switch for receptor-associated drug delivery? (ie: EGFR)
* Glycoproteins role in programmed cell division acting as a master toll-like switch for receptor-associated drug delivery? (ie: EGFR)
* On lipid rafts: "Plasma membranes are heterogeneous and contain microdomains for lipid composition and receptors, especially in T and B lymphocytes and mast cells. Rafts are a way of '''concentrating receptors, the lipids and lipid tethered proteins''' together to provide the elements needed to activate secondary signals." (http://bioweb.wku.edu/courses/biol566/L19SignalPathnonRPTK.html)
* On lipid rafts: "Plasma membranes are heterogeneous and contain microdomains for lipid composition and receptors, especially in T and B lymphocytes and mast cells. Rafts are a way of '''concentrating receptors, the lipids and lipid tethered proteins''' together to provide the elements needed to activate secondary signals." (http://bioweb.wku.edu/courses/biol566/L19SignalPathnonRPTK.html)
 +
* Is the p53 gene dependent on genetical inheritance (DNA-protein interactions) to make epithelial stem cells vulnerable to cancerogenic mutations ?
-
=== Keywords ===
+
== Keywords ==
Src homology domains, SH2, SH3, PH (Pleckstrin Homology domain), cyclosporamide (a alkylating agent used in cancer therapy)
Src homology domains, SH2, SH3, PH (Pleckstrin Homology domain), cyclosporamide (a alkylating agent used in cancer therapy)
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=== References ===
+
== References ==
<biblio>
<biblio>
* 1998 C. Branden, J. Tooze, "Introduction to protein structure", [270-279]
* 1998 C. Branden, J. Tooze, "Introduction to protein structure", [270-279]
</biblio>
</biblio>

Revision as of 08:04, 15 March 2013

EGF(R)-mediated drug delivery

  • First please see this paper for background info on EGF(R) targeting here.
  • Second, the aim of this wiki is to review the characterization of cancerogenic mutations occuring in multiple receptor-associated tyrosine kinase proteins targeting the EGF receptor and perhaps in cholesterol based lipid rafts including stearic acid (monosaturated) and fatty acids derived ligands expressing the Fyn gene.
  • Further, the relationship between MAP kinase signaling cascades and EGFR-mediated over-expression is not fully understood.
  • Thus it is not fully understood how small molecules aggregation (beta-amyloid) can modulate NMDA mediated neuronal distribution in the Hippocampus.

Contents


Glossary

  • cytotoxic: toxicity factor to cells
  • cytoplasm: outer edge of the cell membrane
  • oxidative phosphorylation: a enzymatic reaction converting energy from phosphate cleaving molecules to ATPase and NADPH substrates.
  • Fyn: A cell-dependent tyrosine kinase ligand associated to the Fyn oncogene
  • Src: tyrosine kinase bound protein (GRB2/Ash) encoded by the c-Src gene divided in 3 receptor-associated domains (SH2, SH3, and PH).
  • Tyrosine kinase: Tyrosine specific kinase (enzyme) member of the protein-coding kinases super family.

Case studies

Breast cancer epithelial stem cells switching and the risks of EGF(R)-targeted (Fyn/Src) phosphorylation

Selected readings:

Chemopreventive role of bioflavonoids and endocannabinoids in mitigating long-term oxidative species from EGFR targeted pathway? Study Curcuma Longa...

Questions:

  • Is aerosol-based geoengineering hidden a systemic population control agenda using clouds as the medium and proteases as the cell-based factory for cancerogenic mutations?
    • If so, how can EGFR-based targeting compares to protein phosphatase inhibitor drugs (ie Imidazole) by "selectively" blocking tyrosine kinases phosphorylation ?
  • What other ligases (ATPase/cAMP?) can be metabolized from long-term exposure to a DNA alkylating agent ?
  • Is therefore the chemtrails system hiding in plain sight a pernicious eugenic model for long-term human based experiments on unwary civilians as during the Shoah? (chemotherapy.owl)
  • See also Natural Nitrogen Compounds

Notes:

  • Receptor-associated tyrosine kinase signaling (SH2/SH3) for targeted drug delivery to epithelial stem cells membranes?
    • Calmodulin-dependent protein kinase receptors (Ca2+) signal transduction linked to Alzheimer like neuronal dysregulation? (ie: PH based phospholipid dysregulation) ?
    • Endocannabinoids: Wet Blanket on Hippocampus Excitement: What does this signify for lipid-rafts based EGFR ligands ?
      • Hippocampus dysregulation from calcium-dependent lipid-like signaling networks?
        • Etienne Robillard 08:56, 4 May 2012 (EDT): 420 like (CB1 receptors) to the rescue..? :)
        • In other words, how can anandamide (endocannabinoids) be used as novel therapeutic to mediates neuronal dysregulation of the hippocampus and in particular breast cancer early cancerogenic mutations ?
          • Question: Is AChr dependent protein binding from endocannabinoid-specific activation (CB1-associated?):
          • Endocannabinoid-specific receptors preventing beta amyloid precursors (β-amyloid peptide (Aβ)) aggregating in lipid rafts from cell-protein (AChr) promoted binding site(s), thus autocleaving phospholipid residues from oxidative radicals ? (gp42 link?)
          • Question: How can tyrosine kinase derived substrates (from enzymatic reactions in C-domain (SH2) and N-domain (SH3)) can have a orthogonal role in Alzheimer pathogenesis and in targeted drug delivery?
          • Answer: As emerging hypothesis, phosphorylation-induced tyrosine kinase drug delivery and upregulation to epithelial stem cells may probably result in asymmetrical protein binding in cholesterol-based microdomains (lipid rafts) with ErbB specific ligands, thus triggering a signal transduction cascade from the activated Src/Fyn receptors.

TODO

  • Is programmed cell-death from cell-specific DNA based gene regulation via p53 gene/protein is leading to cell apoptosis? If so, could DNA programmed apoptosis result from aggregated nanoparticles to epithelial/endothelial stem cells membranes (ie: immunoglobin-like domain receptor) ?
  • Glycoproteins role in programmed cell division acting as a master toll-like switch for receptor-associated drug delivery? (ie: EGFR)
  • On lipid rafts: "Plasma membranes are heterogeneous and contain microdomains for lipid composition and receptors, especially in T and B lymphocytes and mast cells. Rafts are a way of concentrating receptors, the lipids and lipid tethered proteins together to provide the elements needed to activate secondary signals." (http://bioweb.wku.edu/courses/biol566/L19SignalPathnonRPTK.html)
  • Is the p53 gene dependent on genetical inheritance (DNA-protein interactions) to make epithelial stem cells vulnerable to cancerogenic mutations ?

Keywords

Src homology domains, SH2, SH3, PH (Pleckstrin Homology domain), cyclosporamide (a alkylating agent used in cancer therapy)

References

  1. C. Branden, J. Tooze, "Introduction to protein structure", [270-279] [1998]
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