TY - JOUR
T1 - Superoxide dismutase is regulated by LAMMER kinase in Drosophila and human cells
AU - James, Brian P.
AU - Staatz, William D.
AU - Wilkinson, Sarah T.
AU - Meuillet, Emmanuelle
AU - Powis, Garth
N1 - Funding Information:
This work was supported by Grant CA077204 from the National Cancer Institute to G.P. and CA096812 to E.M and a T-32 traineeship CA09213 to S.T.W. We thank Leonard Rabinow for fly stocks and sharing unpublished data about Doa, and Marc Brabant for helpful discussions of the data. A portion of this work was carried out in the Model Organism Shared Service at the Arizona Cancer Center.
PY - 2009/3/15
Y1 - 2009/3/15
N2 - 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-Sod or SOD1) 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 SOD1 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.
AB - 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-Sod or SOD1) 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 SOD1 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.
KW - CDC-like kinase
KW - CLK
KW - Drosophila
KW - LAMMER kinase
KW - Superoxide dismutase
KW - TG003
UR - http://www.scopus.com/inward/record.url?scp=60449090746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60449090746&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2008.12.012
DO - 10.1016/j.freeradbiomed.2008.12.012
M3 - Article
C2 - 19135146
AN - SCOPUS:60449090746
SN - 0891-5849
VL - 46
SP - 821
EP - 827
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -