PKCε-mediated ERK1/2 activation involved in radiation-induced cell death in NIH3T3 cells

Yoon Jin Lee, Jae Won Soh, Doo Il Jeoung, Chul Koo Cho, Gil Ja Jhon, Su Jae Lee, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Protein kinase C (PKC) isoforms play distinct roles in cellular functions. We have previously shown that ionizing radiation activates PKC isoforms (α, δ, ε, and ζ), however, isoform-specific sensitivities to radiation and its exact mechanisms in radiation mediated signal transduction are not fully understood. In this study, we showed that overexpression of PKC isoforms (α, δ, ε, and ζ) increased radiation-induced cell death in NIH3T3 cells and PKCε overexpression was predominantly responsible. In addition, PKCε overexpression increased ERK1/2 activation without altering other MAP-kinases such as p38 MAPK or JNK. Co-transfection of dominant negative PKCε (PKCε-KR) blocked both PKCε-mediated ERK1/2 activation and radiation-induced cell death, while catalytically active PKCε construction augmented these phenomena. When the PKCε overexpressed cells were pretreated with PD98059, MEK inhibitor, radiation-induced cell death was inhibited. Co-transfection of the cells with a mutant of ERK1 or -2 (ERK1-KR or ERK2-KR) also blocked these phenomena, and co-transfection with dominant negative Ras or Raf cDNA revealed that PKCε-mediated ERK1/2 activation was Ras-Raf-dependent. In conclusion, PKCε-mediated ERK1/2 activation was responsible for the radiation-induced cell death.

Original languageEnglish
Pages (from-to)219-229
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number2-3
StatePublished - 15 Feb 2003


  • Cell death
  • ERK1/2
  • NIH3T3 cell
  • PKCε
  • Radiation sensitivity


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