User:Etienne Robillard/Notebook/EGFR

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(Breast cancer epithelial stem cells switching and the risks of EGF(R)-targeted (Fyn/Src) phosphorylation)
(Breast cancer epithelial stem cells switching and the risks of EGF(R)-targeted (Fyn/Src) phosphorylation)
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* Signal Transduction Cascades: http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/signals.htm#camp
* 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
* cAMP-dependent protein kinase type I-beta regulatory subunit: http://www.uniprot.org/uniprot/P31321
 +
* 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... ====
==== Chemopreventive role of bioflavonoids and endocannabinoids in mitigating long-term oxidative species from EGFR targeted pathway? Study Curcuma Longa... ====

Revision as of 20:17, 14 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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