Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase

Klaus Dittmann, Claus Mayer, Birgit Fehrenbacher, Martin Schaller, Uma Raju, Luka Milas, David J. Chen, Rainer Kehlbach, H. Peter Rodemann

Research output: Contribution to journalArticle

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Abstract

Ionizing radiation, but not stimulation with epidermal growth factor (EGF), triggers EGF receptor (EGFR) import into the nucleus in a probably karyopherin á-linked manner. An increase in nuclear EGFR is also observed after treatment with H2O2, heat, or cisplatin. During this process, the proteins Ku70/80 and the protein phosphatase 1 are transported into the nucleus. As a consequence, an increase in the nuclear kinase activity of DNA-dependent kinase (DNA-PK) and increased formation of the DNA end-binding protein complexes containing DNA-PK, essential for repair of DNA-strand breaks, occurred. Blockade of EGFR import by the anti-EGFK monoclonal antibody C225 abolished EGFR import into the nucleus and radiation-induced activation of DNA-PK, inhibited DNA repair, and increased radio-sensitivity of treated cells. Our data implicate a novel function of the EGFR during DNA repair processes.

Original languageEnglish (US)
Pages (from-to)31182-31189
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number35
DOIs
StatePublished - Sep 2 2005

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DNA-Activated Protein Kinase
Cell Nucleus Active Transport
Epidermal Growth Factor Receptor
Polynucleotide 5'-Hydroxyl-Kinase
Chemical activation
Radiation
DNA
Phosphotransferases
DNA Repair
Repair
Karyopherins
Protein Phosphatase 1
DNA Breaks
DNA-Binding Proteins
Ionizing Radiation
Radio
Epidermal Growth Factor
Cisplatin
Ionizing radiation
Hot Temperature

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dittmann, K., Mayer, C., Fehrenbacher, B., Schaller, M., Raju, U., Milas, L., ... Rodemann, H. P. (2005). Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. Journal of Biological Chemistry, 280(35), 31182-31189. https://doi.org/10.1074/jbc.M506591200

Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. / Dittmann, Klaus; Mayer, Claus; Fehrenbacher, Birgit; Schaller, Martin; Raju, Uma; Milas, Luka; Chen, David J.; Kehlbach, Rainer; Rodemann, H. Peter.

In: Journal of Biological Chemistry, Vol. 280, No. 35, 02.09.2005, p. 31182-31189.

Research output: Contribution to journalArticle

Dittmann, K, Mayer, C, Fehrenbacher, B, Schaller, M, Raju, U, Milas, L, Chen, DJ, Kehlbach, R & Rodemann, HP 2005, 'Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase', Journal of Biological Chemistry, vol. 280, no. 35, pp. 31182-31189. https://doi.org/10.1074/jbc.M506591200
Dittmann, Klaus ; Mayer, Claus ; Fehrenbacher, Birgit ; Schaller, Martin ; Raju, Uma ; Milas, Luka ; Chen, David J. ; Kehlbach, Rainer ; Rodemann, H. Peter. / Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 35. pp. 31182-31189.
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