Abstract
Epidermal Growth Factor Receptor is a tyrosine kinase receptor that plays a key role in cells. Its ligands contribute to the system modularity by influencing the stability of the dimerized receptor. A synthetically modified ligand could be a potential anti-cancer drug if able to compete with the endogenous ligands while modulating a different pathway activation. Herein, we developed a cross-conservation approach to identify functionally important EGF residues. Four EGF mutants have been selected and studied. These mutants show binding affinities for EGFR similar to EGF, while the effect at the cellular level changed, increasing growth rate in fibroblasts and reducing apoptosis in skin cancer cells. These results support the theory of biased signaling in the tyrosine kinase receptor system.
Abbreviations
- EGF
- Epidermal Growth Factor
- EGFR
- Epidermal Growth Factor Receptor
- PPI
- Protein-Protein Interaction
- MSA
- Multiple Sequence Alignment
- MSTA
- Multiple STructural Alignment
- ITC
- Isothermal Titration Calorimetry
- DMEM
- Dulbecco’s Modified Eagle Medium
- ECD
- Extra Cellular Domain
- WT
- Wild Type