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:
  • Epithelial Stem Cells: Turning over New Leaves (Rockefeller University)
  • 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 ?
        • (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?)
          • Thus how can tyrosine kinase derived substrates (PP2 like pyrimidine?) can have a orthogonal role in Alzheimer pathogenesis and in targeted drug delivery?

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]