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Am J Physiol Renal Physiol (September 9, 2003). doi:10.1152/ajprenal.00144.2003
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Submitted on April 10, 2003
Accepted on August 28, 2003

Renal Expression and Activity of the Germinal Center Kinase, SK2

Andrey V. Cybulsky1*, Tomoko Takano1, Joan Papillon1, Abdelkrim Khadir1, Krikor Bijian1, Chu-Chun Chien2, Charles E. Alpers3, and Hamid Rabb2

1 Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada
2 Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
3 Department of Pathology, University of Washington, Seattle, Washington, USA

* To whom correspondence should be addressed. E-mail: andrey.cybulsky{at}mcgill.ca.

Rat fetal kidney mRNA was analyzed by reverse transcriptase polymerase chain reaction to identify protein kinases. This screening demonstrated expression of a protein kinase consistent with SK2, a group II germinal center kinase, and homolog of human Ste20-like kinase (SLK). SK2 mRNA, protein expression and kinase activity were increased in rat fetal kidney homogenates (embryonic days 17-21), as compared with adult control. In adult kidneys subjected to cross-clamping of the renal artery, followed by reperfusion, SK2 mRNA, protein expression and kinase activity were increased, as compared with untreated contralateral control. By immunohistochemistry, SK2 expression was evident mainly in the cytoplasm of tubular epithelial cells in fetal and adult kidneys. There was also some expression in developing and mature podocytes, but staining of the interstitium was negative. In cultured renal tubular epithelial cells, SK2 kinase activity was increased after incubation with serum, or after exposure to chemical anoxia plus re-exposure to glucose. Stable overexpression of SLK reduced cell proliferation and increased apoptosis, and exacerbated apoptosis and necrosis after chemical anoxia plus re-exposure to glucose. Thus, SK2 is a renal epithelial protein kinase, whose expression and activity are increased during development, as well as recovery from acute renal failure, where tubular epithelial regeneration may recapitulate developmental processes. The actions of SK2 appear to be anti-proliferative, and may facilitate cell injury.




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