DNA-dependent protein kinase-mediated phosphorylation of protein kinase B requires a specific recognition sequence in the C-terminal hydrophobic motif.
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Park, Jongsun, Feng, Jianhua, Li, Yuwen, Hammarsten, Ola, Brazil, Derek Patrick and Hemmings, Brian Arthur (2009) DNA-dependent protein kinase-mediated phosphorylation of protein kinase B requires a specific recognition sequence in the C-terminal hydrophobic motif. The Journal of Biological Chemistry, 284 (10). pp. 6169-6174. ISSN 0021-9258
Abstract
DNA-dependent protein kinase (DNA-PK) has been implicated in a variety of nuclear processes including DNA double strand break repair, V(D)J recombination, and transcription. A recent study showed that DNA-PK is responsible for Ser-473 phosphorylation in the hydrophobic motif of protein kinase B (PKB/Akt) in genotoxic-stressed cells, suggesting a novel role for DNA-PK in cell signaling. Here, we report that DNA-PK activity toward PKB peptides is impaired in DNA-PK knock-out mouse embryonic fibroblast cells when compared with wild type. In addition, human glioblastoma cells expressing a mutant form of DNA-PK (M059J) displayed a lower DNA-PK activity when compared with glioblastoma cells expressing wild-type DNA-PK (M059K) when PKB peptide substrates were tested. DNA-PK preferentially phosphorylated PKB on Ser-473 when compared with its known in vitro substrate, p53. A consensus hydrophobic amino acid surrounding the Ser-473 phospho-acceptor site in PKB containing amino acids Phe at position +1 and +4 and Tyr at position -1 are critical for DNA-PK activity. Thus, these data define the specificity of DNA-PK action as a Ser-473 kinase for PKB in DNA repair signaling.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
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| Date Deposited: | 14 Dec 2009 13:50 |
| Last Modified: | 31 Jan 2013 01:02 |
| URI: | https://oak.novartis.com/id/eprint/959 |