User:Etienne Robillard/Notebook/EGFR

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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].
* First please see this paper for background info on EGF(R) targeting [http://nrresource.org/Pathways/VDR%20Targets/92391.html here].
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* The aim of this wiki document is to review the characterization of cancerogenic mutations occuring in multiple receptor-associated tyrosine kinase proteins targeting the EGF receptor and perhaps cholesterol based lipid rafts including stearic acid (monosaturated) and in fatty acids derived ligands.
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* 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.
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* 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.
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* Thus it is not fully understood how small molecules aggregation (beta-amyloid) can modulate NMDA mediated neuronal distribution in the Hippocampus.
   
   
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__TOC__
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=== Glossary ===
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* cytotoxic: toxicity factor to cells
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* cytoplasm: outer edge of the cell membrane
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* oxidative phosphorylation: a enzymatic reaction converting energy from phosphate cleaving molecules to ATPase and NADPH substrates.
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* 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 (SH2/SH3) for targeted drug delivery to epithelial stem cells membranes?
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Selected readings:
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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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* [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
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* 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
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** 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.
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* Amyloid beta A4 protein: http://www.uniprot.org/uniprot/P05067
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==== Chemopreventive role of bioflavonoids and endocannabinoids in mitigating long-term oxidative species from EGFR targeted pathway? Study Curcuma Longa... ====
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Questions:
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* 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?
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** If so, how can EGFR-based targeting compares to protein phosphatase inhibitor drugs (ie Imidazole) by "selectively" blocking tyrosine kinases phosphorylation ?
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* What other ligases (ATPase/cAMP?) can be metabolized from long-term exposure to a DNA alkylating agent ?
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* 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) 
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* See also [http://chemwiki.ucdavis.edu/Organic_Chemistry/Virtual_Textbook_of_OChem/Amines/Nomenclature_and_Structure_of_Amines/Natural_Nitrogen_Compounds Natural Nitrogen Compounds]
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Notes:
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* '''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) ?
** Calmodulin-dependent protein kinase receptors (Ca2+) signal transduction linked to Alzheimer like neuronal dysregulation? (ie: PH based phospholipid dysregulation) ?
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** [http://www.alzforum.org/new/detail.asp?id=1446 Endocannabinoids: Wet Blanket on Hippocampus Excitement]
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** [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?  
*** '''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..? :)
**** [[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 ?
**** 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 ?
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***** (AChe)-dependent protein binding from endocannabinoid-specific activation (CB1-associated?):  
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***** Question: Is AChr dependent protein binding from endocannabinoid-specific activation (CB1-associated?):  
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***** Endocannabinoid-specific receptors preventing beta amyloid precursors (β-amyloid peptide (Aβ)) aggregating in lipid rafts from cell-protein (AChe) promoted binding site(s), thus autocleaving phospholipid residues from oxidative radicals ? (gp42 link?)
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***** 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?
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***** 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 ==
== TODO ==

Current revision

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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