Phospholipase C-ϵ Augments Epidermal Growth Factor-dependent Cell Growth by Inhibiting Epidermal Growth Factor Receptor Down-regulation
The down-regulation of the epidermal growth factor (EGF) receptor is critical for the termination of EGF-dependent signaling, and the dysregulation of this process can lead to oncogenesis. In the present study, we suggest a novel mechanism for the regulation of EGF receptor down-regulation by phosph...
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| Veröffentlicht in: | The Journal of biological chemistry 2008-01, Vol.283 (1), p.341-349 |
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| creator | Yun, Sanguk Hong, Won-Pyo Choi, Jang Hyun Yi, Kye Sook Chae, Suhn-Kee Ryu, Sung Ho Suh, Pann-Ghill |
| description | The down-regulation of the epidermal growth factor (EGF) receptor is critical for the termination of EGF-dependent signaling, and the dysregulation of this process can lead to oncogenesis. In the present study, we suggest a novel mechanism for the regulation of EGF receptor down-regulation by phospholipase C-ϵ. The overexpression of PLC-ϵ led to an increase in receptor recycling and decreased the down-regulation of the EGF receptor in COS-7 cells. Adaptor protein complex 2 (AP2) was identified as a novel binding protein that associates with the PLC-ϵ RA2 domain independently of Ras. The interaction of PLC-ϵ with AP2 was responsible for the suppression of EGF receptor down-regulation, since a perturbation in this interaction abolished this effect. Enhanced EGF receptor stability by PLC-ϵ led to the potentiation of EGF-dependent growth in COS-7 cells. Finally, the knockdown of PLC-ϵ in mouse embryo fibroblast cells elicited a severe defect in EGF-dependent growth. Our results indicated that PLC-ϵ could promote EGF-dependent cell growth by suppressing receptor down-regulation. |
| doi_str_mv | 10.1074/jbc.M704180200 |
| format | Article |
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In the present study, we suggest a novel mechanism for the regulation of EGF receptor down-regulation by phospholipase C-ϵ. The overexpression of PLC-ϵ led to an increase in receptor recycling and decreased the down-regulation of the EGF receptor in COS-7 cells. Adaptor protein complex 2 (AP2) was identified as a novel binding protein that associates with the PLC-ϵ RA2 domain independently of Ras. The interaction of PLC-ϵ with AP2 was responsible for the suppression of EGF receptor down-regulation, since a perturbation in this interaction abolished this effect. Enhanced EGF receptor stability by PLC-ϵ led to the potentiation of EGF-dependent growth in COS-7 cells. Finally, the knockdown of PLC-ϵ in mouse embryo fibroblast cells elicited a severe defect in EGF-dependent growth. 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In the present study, we suggest a novel mechanism for the regulation of EGF receptor down-regulation by phospholipase C-ϵ. The overexpression of PLC-ϵ led to an increase in receptor recycling and decreased the down-regulation of the EGF receptor in COS-7 cells. Adaptor protein complex 2 (AP2) was identified as a novel binding protein that associates with the PLC-ϵ RA2 domain independently of Ras. The interaction of PLC-ϵ with AP2 was responsible for the suppression of EGF receptor down-regulation, since a perturbation in this interaction abolished this effect. Enhanced EGF receptor stability by PLC-ϵ led to the potentiation of EGF-dependent growth in COS-7 cells. Finally, the knockdown of PLC-ϵ in mouse embryo fibroblast cells elicited a severe defect in EGF-dependent growth. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Cell Line Cell Line, Tumor Cell Proliferation - drug effects Chlorocebus aethiops COS Cells Down-Regulation - drug effects Epidermal Growth Factor - pharmacology ErbB Receptors - genetics ErbB Receptors - metabolism Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism HeLa Cells Humans Immunoprecipitation Mice Microscopy, Confocal Phosphoinositide Phospholipase C - antagonists & inhibitors Phosphoinositide Phospholipase C - genetics Phosphoinositide Phospholipase C - metabolism Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism RNA, Small Interfering - genetics Thymidine - metabolism Transfection Two-Hybrid System Techniques |
| title | Phospholipase C-ϵ Augments Epidermal Growth Factor-dependent Cell Growth by Inhibiting Epidermal Growth Factor Receptor Down-regulation |
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