Phospholipase C-epsilon augments epidermal growth factor-dependent cell growth by inhibiting epidermal growth factor receptor down-regulation.

Abstract

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-epsilon. The overexpression of PLC-epsilon 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-epsilon RA2 domain independently of Ras. The interaction of PLC-epsilon 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-epsilon led to the potentiation of EGF-dependent growth in COS-7 cells. Finally, the knockdown of PLC-epsilon in mouse embryo fibroblast cells elicited a severe defect in EGF-dependent growth. Our results indicated that PLC-epsilon could promote EGF-dependent cell growth by suppressing receptor down-regulation.

• Authors: Sanguk Yun, Won-Pyo Hong, Jang Hyun Choi, Kye Sook Yi, Suhn-Kee Chae, Sung Ho Ryu, Pann-Ghill Suh
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 283 Issue 1 Pg. 341-349 (Jan 04 2008) ISSN: 0021-9258 [Print] United States
• PMID: 17956867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Recombinant Fusion Proteins
• Green Fluorescent Proteins
• Epidermal Growth Factor
• ErbB Receptors
• Phosphoinositide Phospholipase C
• phospholipase C epsilon
• Thymidine

Topics

• Animals
• COS Cells
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chlorocebus aethiops
• Down-Regulation (drug effects)
• Epidermal Growth Factor (pharmacology)
• ErbB Receptors (genetics, metabolism)
• Green Fluorescent Proteins (genetics, metabolism)
• HeLa Cells
• Humans
• Immunoprecipitation
• Mice
• Microscopy, Confocal
• Phosphoinositide Phospholipase C (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (genetics)
• Recombinant Fusion Proteins (genetics, metabolism)
• Thymidine (metabolism)
• Transfection
• Two-Hybrid System Techniques