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KMID : 0379520080240030175
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한국독성학회지
2008 Volume.24 No. 3 p.175 ~ p.182
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Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System
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Yuwen Li
Kim Jeong-Lan
Yang Keum-Jin
Piao Longzhen
Cho Jae-Youl
Shin Sang-Hee
Shin Eul-Soon
Park Kyung-Ah
Byu Hee-Sun
Won Min-Ho
Choi Byung-Lyul
Lee Hyun-Ji
Kim Young-Rae
Hong Jang-Hee
Hur Gang-Min
Park Jong-Sun
Seok Jeong-Ho
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Abstract
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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 2nd 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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KEYWORD
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DNA-PK, DNA damage, Protein kinase B, Insulin signaling, Cell Signaling
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