| Autor: |
Gabriel G. Haddad, Robert J. Davidson, Sarah J. Parsons, Icksoo Lee, Tsuyoshi Miyake, Robert M. Douglas, Michelle L. Demory, Julie L. Boerner, Maik Hüttemann, William Faust |
| Rok vydání: |
2009 |
| Předmět: |
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| Zdroj: |
Journal of Biological Chemistry. 284:36592-36604 |
| ISSN: |
0021-9258 |
| DOI: |
10.1074/jbc.m109.000760 |
| Popis: |
Co-overexpression of the epidermal growth factor (EGF) receptor (EGFR) and c-Src frequently occurs in human tumors and is linked to enhanced tumor growth. In experimental systems this synergistic growth requires EGF-dependent association of c-Src with the EGFR and phosphorylation of Tyr-845 of the receptor by c-Src. A search for signaling mediators of Tyr(P)-845 revealed that mitochondrial cytochrome c oxidase subunit II (CoxII) binds EGFR in a Tyr(P)-845- and EGF-dependent manner. In cells this association involves translocation of EGFR to the mitochondria, but regulation of this process is ill-defined. The current study demonstrates that c-Src translocates to the mitochondria with similar kinetics as EGFR and that the catalytic activity of EGFR and c-Src as well as endocytosis and a mitochondrial localization signal are required for these events. CoxII can be phosphorylated by EGFR and c-Src, and EGF stimulation reduces Cox activity and cellular ATP, an event that is dependent in large part on EGFR localized to the mitochondria. These findings suggest EGFR plays a novel role in modulating mitochondrial function via its association with, and modification of CoxII. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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