User:Tkadm30/Notebook/EGFR

EGF(R)-mediated drug delivery

• First please see this paper for background info on EGF(R) targeting here.
• 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.

Case studies

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

Selected readings:

• Epithelial Stem Cells: Turning over New Leaves (Rockefeller University)

Fyn (Src) lipid based drug delivery and breast cancer: Chemtrails as potentially harmful cancerogenic agents?

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
    • 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 AChe 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 (AChe) 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 assymetrical protein binding on SH2 and SH3 domains in cholesterol based microdomains (lipid rafts) with ErbB specific ligands.

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]