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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sousa, Leiliane P. Lax, Irit De Camilli, Pietro Ferguson, Shawn M. Shen, Hongying Schlessinger, Joseph |
| Description | Author Affiliation: Sousa LP ( Departments of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.); |
| Abstract | The role of endocytosis in the control of EGF receptor (EGFR) activation and cell signaling was explored by using mouse fibroblasts in which dynamin was conditionally depleted. Dynamin is a GTPase shown to play an important role in the control clathrin mediated endocytosis of EGFR and other cell surface receptors. In this report, we demonstrate that EGF binding activity and the display of high and low affinity EGFRs on the cell surface are not affected by dynamin depletion. By contrast, dynamin depletion leads to a strong inhibition of EGFR endocytosis, robust enhancement of EGFR autophosphorylation and ubiquitination, and slower kinetics of EGFR degradation. Surprisingly, MAPK stimulation induced by either low or high EGF concentrations is not affected by dynamin depletion. While a similar initial Akt response is detected in control or dynamin depleted fibroblasts, a somewhat more sustained Akt stimulation is detected in the dynamin depleted cells. These experiments demonstrate that dynamin-mediated endocytosis leads to attenuation of EGFR activation and degradation and that stimulation of the MAPK response and Akt activation are primarily mediated by activated EGFR located in the plasma membrane. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Membrane Metabolism Dynamins Receptor, Epidermal Growth Factor Animals Clathrin Endocytosis Epidermal Growth Factor Genetics Fibroblasts Cytology GTP Phosphohydrolases Ligands Mice Mice, Knockout Mice, Transgenic Models, Biological Phosphorylation Signal Transduction Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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