Function of erbB receptors and DNA-PKcs on phosphorylation of cytoplasmic and nuclear Akt at S473 induced by erbB1 ligand and ionizing radiation

Mahmoud Toulany, Tim Andre Schickfluß, Kazi R. Fattah, Kyung Jong Lee, Benjamin P C Chen, Birgit Fehrenbacher, Martin Schaller, David J. Chen, H. Peter Rodemann

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background and purpose: In the present study effect of erbB2 as well as DNA-PKcs on ionizing radiation (IR)- and erbB1 ligand-induced phosphorylation of Akt at S473 in cytoplasmic and nuclear fractions was investigated. Materials and methods: DNA-PKcs proficient and deficient syngeneic colon carcinoma sublines of HCT116 and the glioblastoma cell lines MO59K and MO59J as well as the lung carcinoma cell line A549 were used. Akt-S473 phosphorylation was investigated in cells pre-treated with pharmacological inhibitors or transfected with siRNA by immunoprecipitation, Western blotting and confocal microscopy after different stimuli, i.e., ligands and IR. Results: IR-induced phosphorylation of Akt in both MO59K and MO59J cell lines but not in HCT116 cells was DNA-PKcs dependent. In A549 cells, IR-induced phosphorylation of nuclear Akt-S473 was dependent on erbB1, erbB2, and DNA-PKcs. EGF induced phosphorylation of nuclear Akt-S473 in a DNA-PKcs and erbB2 independent manner. Conclusion: Data indicate that the function of DNA-PKcs on IR-induced Akt-S473 phosphorylation is cell line specific. IR-induced, but not EGF-induced phosphorylation of cytoplasmic and/or nuclear Akt-S473 is erbB2 dependent.

Original languageEnglish (US)
Pages (from-to)140-146
Number of pages7
JournalRadiotherapy and Oncology
Volume101
Issue number1
DOIs
StatePublished - Oct 1 2011

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Keywords

  • DNA-PKcs
  • Ionizing radiation
  • P-Akt (S473)
  • erbB1-ligands

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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