| Autor: |
Walker, Francesca, Rothacker, Julie, Henderson, Christine, Nice, Edouard C., Catimel, Bruno, Zhang, Hui-Hua, Scott, Andrew M., Bailey, Michael F., Orchard, Suzanne G., Adams, Timothy E., Liu, Zhanqi, Garrett, Thomas P.J., Clayton, Andrew H.A., Burgess, Antony W. |
| Zdroj: |
Growth Factors; Dec2012, Vol. 30 Issue 6, p394-409, 16p |
| Abstrakt: |
The activation of the epidermal growth factor receptor (EGFR) kinase requires ligand binding to the extracellular domain (ECD). Previous reports demonstrate that the EGFR-ECD can be crystallized in two conformations - a tethered monomer or, in the presence of ligand, an untethered back-to-back dimer. We use Biosensor analysis to demonstrate that even in the monomeric state different C-terminal extensions of both truncated (EGFR1-501)-ECD and full-length EGFR1-621-ECD can change the conformation of the ligand-binding site. The binding of a monoclonal antibody mAb806, which recognizes the dimer interface, to the truncated EGFR1-501-Fc fusion protein is reduced in the presence of ligand, consistent with a change in conformation. On the cell surface, the presence of erythroblastosis B2 (erbB2) increases the binding of mAb806 to the EGFR. The conformation of the erbB2: EGFR heterodimer interface changes when the cells are treated with epidermal growth factor (EGF). We propose that ligand induces kinase-inactive, pre-formed EGFR dimers and heterodimers to change conformation leading to kinase-active tetramers, where kinase activation occurs via an asymmetric interaction between EGFR dimers. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
