Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 46, Issue 6, Pages 821-827Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2008.12.012
Keywords
LAMMER kinase; Superoxide dismutase; CDC-like kinase; CLK; TG003; Drosophila
Funding
- National Cancer Institute [CA077204]
- [CA096812]
- [CA09213]
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LAMMER kinases (also known as CDC-2-like or CLKs) are a family of dual specificity serine/threonine protein kinases that are found in all sequenced eukaryotic genomes. In the fission yeast, Schizosaccharomyces pombe, the LAMMER kinase gene, Lkh1, positively regulates the expression of the antioxidant defense genes, Superoxide dismutase1 (sod1+, CuZn-SOD) and catalase (ctt1+, CAT). We have Shown that Mutations in the Drosophila LAMMER kinase gene, Darkener of apricot (Doa), protect against the decrease in life span caused by the reactive oxygen species (ROS) generator paraquat, and at the same time show an increase in cytoplasmic (CuZn center dot Sod or SOD-I) and mitochondrial Superoxide dismutase (Mn-Sod or SOD2) protein levels and activity. The siRNA-mediated knock down of the human LAMMER kinase gene, CLK-1, in HeLa and MCF-7 human cell lines leads to an increase in both SOD I activity and mRNA transcript levels. These data Suggest that SOD1 is negatively regulated by LAMMER kinases in Drosophila and human cell lines and that this regulation may be conserved during evolution. (c) 2008 Elsevier Inc. All rights reserved.
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