User:Tkadm30/Notebook/EGFR: Difference between revisions
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Selected readings: | Selected readings: | ||
* [http://jn.nutrition.org/content/137/3/548 (n-3) PUFA Alter Raft Lipid Composition and Decrease Epidermal Growth Factor Receptor Levels in Lipid Rafts of Human Breast Cancer Cells] | |||
* [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408375/ Epithelial Stem Cells: Turning over New Leaves] (Rockefeller University) | * [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408375/ Epithelial Stem Cells: Turning over New Leaves] (Rockefeller University) | ||
* [http://www.uniprot.org/uniprot/P06241 Fyn (EC 2.7.10.2)] | * [http://www.uniprot.org/uniprot/P06241 Fyn (EC 2.7.10.2)] | ||
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* Amyloid beta A4 protein: http://www.uniprot.org/uniprot/P05067 | * Amyloid beta A4 protein: http://www.uniprot.org/uniprot/P05067 | ||
==== Chemopreventive role of bioflavonoids and endocannabinoids | ==== Chemopreventive role of bioflavonoids and endocannabinoids ==== | ||
Questions: | 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 | * endocannabinoids as metaplastic neuronal activitor ? (chemopreventive effect) | ||
* in mitigating long-term oxidative species from EGFR targeted pathway? (lipid rafts?) | |||
* '''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? | |||
* What other ligases (ATPase/cAMP?) can be metabolized from long-term exposure to a DNA alkylating agent ? | * 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) | * 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) |
Revision as of 16:05, 10 December 2014
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.
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:
- (n-3) PUFA Alter Raft Lipid Composition and Decrease Epidermal Growth Factor Receptor Levels in Lipid Rafts of Human Breast Cancer Cells
- Epithelial Stem Cells: Turning over New Leaves (Rockefeller University)
- Fyn (EC 2.7.10.2)
- 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 catalytic subunit alpha: http://www.uniprot.org/uniprot/P17612
- 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
Questions:
- endocannabinoids as metaplastic neuronal activitor ? (chemopreventive effect)
- in mitigating long-term oxidative species from EGFR targeted pathway? (lipid rafts?)
- 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?
- 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.
- Hippocampus dysregulation from calcium-dependent lipid-like signaling networks?
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
-
C. Branden, J. Tooze, "Introduction to protein structure", [270-279]