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Phospholipase C-epsilon augments epidermal growth factor-dependent cell growth by inhibiting epidermal growth factor

Sanguk Yun1, Won-Pyo Hong1, Jang Hyun Choi1

  • 1Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, Kyung-Buk 790-784, Republic of Korea and the.

The Journal of Biological Chemistry
|October 25, 2007
PubMed

Insights

Phospholipase C-epsilon (PLC-epsilon) regulates epidermal growth factor (EGF) receptor levels. PLC-epsilon suppresses EGF receptor down-regulation, enhancing EGF-dependent cell growth.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncogenesis

Background:

  • Epidermal growth factor (EGF) receptor down-regulation terminates EGF signaling.
  • Dysregulation of EGF receptor down-regulation is implicated in cancer development.
  • A novel mechanism for EGF receptor regulation is investigated.

Purpose of the Study:

  • To elucidate the role of phospholipase C-epsilon (PLC-epsilon) in EGF receptor regulation.
  • To identify novel binding partners of PLC-epsilon involved in receptor trafficking.
  • To determine the impact of PLC-epsilon on EGF-dependent cell proliferation.

Main Methods:

  • Overexpression and knockdown of PLC-epsilon in mammalian cell lines (COS-7, mouse embryo fibroblasts).
  • Analysis of EGF receptor recycling and down-regulation.
  • Co-immunoprecipitation assays to identify protein interactions, including PLC-epsilon and Adaptor protein complex 2 (AP2).

Main Results:

  • PLC-epsilon overexpression increased EGF receptor recycling and decreased its down-regulation.
  • AP2 was identified as a novel binding protein for PLC-epsilon, independent of Ras.
  • Disruption of the PLC-epsilon-AP2 interaction abrogated the suppression of EGF receptor down-regulation.
  • PLC-epsilon enhanced EGF-dependent cell growth by stabilizing the EGF receptor.
  • PLC-epsilon knockdown resulted in impaired EGF-dependent growth.

Conclusions:

  • PLC-epsilon suppresses EGF receptor down-regulation through interaction with AP2.
  • This mechanism promotes EGF-dependent cell growth by maintaining EGF receptor stability.
  • PLC-epsilon represents a potential therapeutic target in cancers driven by EGF signaling.

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