Phospholipase C-epsilon augments epidermal growth factor-dependent cell growth by inhibiting epidermal growth factor receptor down-regulation
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- Phospholipase C-epsilon augments epidermal growth factor-dependent cell growth by inhibiting epidermal growth factor receptor down-regulation
- Yun, Sanguk; Hong, Won-Pyo; Choi, Jang Hyun; Yi, Kye Sook; Chae, Suhn-Kee; Ryu, Sung Ho; Suh, Pann-Ghill
- Issue Date
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.283, no.1, pp.341 - 349
- 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.
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