Activation of ERK during DNA damage-induced apoptosis involves protein kinase Cdelta

Biochem Biophys Res Commun. 2005 Sep 9;334(4):1068-73. doi: 10.1016/j.bbrc.2005.06.199.


We have previously shown that protein kinase C (PKC) acts upstream of caspases to regulate cisplatin-induced apoptosis. Since extracellular signal-regulated kinases (ERKs) have also been implicated in DNA damage-induced apoptosis, we have examined if ERK signaling pathway acts downstream of PKC in the regulation of cisplatin-induced apoptosis. PKC activator PDBu induced ERK1/2 phosphorylation which was inhibited by general PKC inhibitor bisindolylmaleimide and Gö 6983 as well as the MEK inhibitor U0126 but not by the PKCdelta inhibitor rottlerin. Cisplatin caused a concentration-dependent activation of ERK1/2 in HeLa cells. The level of ERK2 was decreased in HeLa cells that acquired resistance to cisplatin (HeLa/CP). The MEK inhibitor U0126 inhibited cisplatin-induced ERK activation and attenuated cisplatin-induced cell death. Inhibition of PKCdelta by rottlerin or depletion of PKCdelta by siRNA inhibited cisplatin-induced ERK activation. These results suggest that cisplatin-induced DNA damage results in activation of ERK1/2 via PKCdelta.

MeSH terms

  • Apoptosis*
  • Cisplatin / pharmacology*
  • DNA Damage*
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • HeLa Cells
  • Humans
  • Protein Kinase C / metabolism*
  • Protein Kinase C-delta
  • Signal Transduction / drug effects


  • PRKCD protein, human
  • Protein Kinase C
  • Protein Kinase C-delta
  • Extracellular Signal-Regulated MAP Kinases
  • Cisplatin