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

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