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| Content Provider | PubMed Central |
|---|---|
| Author | Özcan, Ferruh Klein, Peter Lemmon, Mark A. Lax, Irit Schlessinger, Joseph |
| Copyright Year | 2006 |
| Abstract | The small subpopulation of high-affinity EGF receptors (EGFRs) on living cells revealed by Scatchard analysis of 125I-EGF binding results was discovered nearly three decades ago, yet not much is known about the underlying mechanism. After the determination of the structure of different forms of EGFR extracellular domain it was proposed that the monomeric tethered configuration corresponds to the majority of low-affinity receptors, whereas the extended dimeric configuration corresponds to the minority of the high-affinity class of EGFRs. Mathematical modeling of EGF-binding experiments to different conformational mutants of EGFR has shown that the high-affinity class of EGFR on living cells does not correspond to the extended configuration of EGFR and can only be accounted for by including in the mathematical model an additional binding event that is attributed to the dynamic nature of EGFR on living cells. To circumvent this problem we have performed similar experiments in the background of an EGFR mutant that does not form high-affinity sites. Quantitative analysis and mathematical modeling of these data show that release of the intramolecular tether causes a 2-fold increase in EGF-binding affinity, whereas elimination of the dimerization arm reduces EGF-binding affinity by ≈6-fold. These experiments confirm the salient features of the structural model for EGFR regulation and argue further that the intramolecular tether provides only limited autoinhibitory control of EGFR activity and that the low-affinity class of EGF-binding sites on living cells reflects interconverting, tethered, and extended receptor configurations. |
| Related Links | http://dx.doi.org/10.1073/pnas.0601469103 |
| Ending Page | 5740 |
| Page Count | 6 |
| Starting Page | 5735 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-04-11 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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