Toxicological Research

  • 제24권3호
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  • Pages.175-182
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  • 2008
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
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DOI QR코드

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Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System

  • Li, Yuwen (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Piao, Longzhen (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Yang, Keum-Jin (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Shin, Sang-Hee (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Shin, Eul-Soon (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Park, Kyung-Ah (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Byun, Hee-Sun (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Won, Min-Ho (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Choi, Byung-Lyul (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Lee, Hyun-Ji (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Kim, Young-Rae (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Hong, Jang-Hee (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Hur, Gang-Min (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Kim, Jeong-Lan (Department of Psychiatry, College of Medicine, Chungnam National University) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Seok, Jeong-Ho (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences) ;
  • Park, Jong-Sun (Department of Pharmacology, Cell Signaling Laboratory, Research Center for Transgenic Cloned Pigs, Daejeon Regional Cancer Center, Cancer Research Institute, Research Institute for Medical Sciences)
  • 발행 : 2008.09.01
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초록

DNA-dependent protein kinase(DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be $2^{nd}$ upstream kinase for protein kinase B(PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells(MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK(M059J) and a wild-type of DNA-PK(M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.

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참고문헌

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피인용 문헌

  1. Genomic Approach to Understand the Association of DNA Repair with Longevity and Healthy Aging Using Genomic Databases of Oldest-Old Population vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/2984730