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PKCε acts as negative allosteric modulator of EGF receptor signalling

Simona Weisheit1, Claudia Schäfer, Carmen Mertens

  • 1Center of Molecular Biomedicine, Institute of Biochemistry and Biophysics, Friedrich-Schiller-University Jena, Jena, Germany.

Cellular Signalling
|October 23, 2010
PubMed

Insights

High levels of Protein kinase C epsilon (PKCε) in cancer cells can inhibit the Epidermal Growth Factor Receptor (EGFR) signaling pathway. This novel function suggests PKCε acts as an allosteric modulator, impacting cell proliferation and invasion.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Signaling

Background:

  • Protein kinase C epsilon (PKCε) is recognized as a transforming oncogene involved in key cellular functions.
  • PKCε has a known role as a scaffold protein, linking PLCγ1 to the Epidermal Growth Factor Receptor (EGFR) signaling module.

Purpose of the Study:

  • To investigate the role of over-expressed PKCε in head and neck squamous carcinoma (HNSCC) cell lines.
  • To elucidate the mechanism by which PKCε affects EGFR signaling pathways and cell proliferation.

Main Methods:

  • Utilized the HNSCC cell line FaDu and three additional HNSCC cell lines.
  • Assessed the association between PKCε and EGFR.
  • Analyzed the impact of PKCε on PLCγ1 recruitment, activation, and downstream signaling pathways (ERK, Akt).

Main Results:

  • Over-expressed PKCε associates with EGFR in FaDu cells, inhibiting PLCγ1 recruitment and EGF-mediated proliferation.
  • These effects are independent of PKCε's catalytic or scaffold activity, depending solely on its expression level.
  • In other HNSCC lines, over-expressed PKCε inhibits EGFR signaling pathways (ERK, PLCγ1, Akt) to varying degrees.

Conclusions:

  • Highly expressed PKCε functions as a negative allosteric modulator of EGFR signaling in certain carcinoma cells.
  • This study reveals a novel mechanism where PKCε modulates EGFR signaling, suggesting EGFR as a target for allosteric modulation by accessory proteins.

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